[Senate Hearing 113-487]
[From the U.S. Government Publishing Office]


                                                        S. Hrg. 113-487
 

                    TAKING A TOLL ON FAMILIES AND THE
           ECONOMY: THE RISING COST OF ALZHEIMER'S IN AMERICA

=======================================================================

                                HEARING

                                before a

                          SUBCOMMITTEE OF THE

            COMMITTEE ON APPROPRIATIONS UNITED STATES SENATE

                    ONE HUNDRED THIRTEENTH CONGRESS

                             SECOND SESSION

                               __________

                            SPECIAL HEARING

                   FEBRUARY 26, 2014--WASHINGTON, DC

                               __________

         Printed for the use of the Committee on Appropriations


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        committee.action?chamber=senate&committee=appropriations

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                      COMMITTEE ON APPROPRIATIONS

               BARBARA A. MIKULSKI, Maryland, Chairwoman
PATRICK J. LEAHY, Vermont            RICHARD C. SHELBY, Alabama, Vice
TOM HARKIN, Iowa                         Chairman
PATTY MURRAY, Washington             THAD COCHRAN, Mississippi
DIANNE FEINSTEIN, California         MITCH McCONNELL, Kentucky
RICHARD J. DURBIN, Illinois          LAMAR ALEXANDER, Tennessee
TIM JOHNSON, South Dakota            SUSAN M. COLLINS, Maine
MARY L. LANDRIEU, Louisiana          LISA MURKOWSKI, Alaska
JACK REED, Rhode Island              LINDSEY GRAHAM, South Carolina
MARK L. PRYOR, Arkansas              MARK KIRK, Illinois
JON TESTER, Montana                  DANIEL COATS, Indiana
TOM UDALL, New Mexico                ROY BLUNT, Missouri
JEANNE SHAHEEN, New Hampshire        JERRY MORAN, Kansas
JEFF MERKLEY, Oregon                 JOHN HOEVEN, North Dakota
MARK BEGICH, Alaska                  MIKE JOHANNS, Nebraska
CHRISTOPHER A. COONS, Delaware       JOHN BOOZMAN, Arkansas

                   Charles E. Kieffer, Staff Director
             William D. Duhnke III, Minority Staff Director
                                 ------

 Subcommittee on Departments of Labor, Health and Human Services, and
                    Education, and Related Agencies

                       TOM HARKIN, Iowa, Chairman
PATTY MURRAY, Washington             JERRY MORAN, Kansas
MARY L. LANDRIEU, Louisiana          THAD COCHRAN, Mississippi
RICHARD J. DURBIN, Illinois          RICHARD C. SHELBY, Alabama
JACK REED, Rhode Island              LAMAR ALEXANDER, Tennessee
MARK L. PRYOR, Arkansas              LINDSEY GRAHAM, South Carolina
BARBARA A. MIKULSKI, Maryland        MARK KIRK, Illinois
JON TESTER, Montana                  MIKE JOHANNS, Nebraska
JEANNE SHAHEEN, New Hampshire        JOHN BOOZMAN, Arkansas
JEFF MERKLEY, Oregon

                           Professional Staff

                            Adrienne Hallett
                              Mark Laisch
                             Lisa Bernhardt
                            Michael Gentile
                             Robin Juliano
                              Kelly Brown
                      Laura A. Friedel (Minority)
                      Jennifer Castagna (Minority)
                          Chol Pak (Minority)
                         M.V. Young (Minority)

                         Administrative Support

                              Teri Curtin


                            C O N T E N T S

                              ----------
                                                                   Page

Opening Statement of Senator Tom Harkin..........................     1
    Prepared Statement...........................................     3
Statement of Senator Jerry Moran.................................     4
Statement of Francis S. Collins, M.D., Ph.D., Director, National
  Institutes of Health, Department of Health and Human Services;
  accompanied by Richard J. Hodes, M.D., Director, National
  Institute on Aging; and Story C. Landis, Ph.D., Director,
  National Institute of Neurlogical Disorders and Stroke.........     6
    Prepared Statement...........................................    10
Statement of Dennis Moore, Former U.S. Congressman From the Third
  District of Kansas.............................................    30
    Prepared Statement...........................................    32
Statement of Dr. Michael Hurd, Director, Rand Center for the
  Study of Aging.................................................    35
    Prepared Statement...........................................    37
Statement of Seth Rogen, Stand-Up Comedian, Actor, Producer,
  Director, Screenwriter, Voice Actor............................    39
    Prepared Statement...........................................    42
Prepared Statement of Senator Susan M. Collins...................    51
Prepared Statement of Senator Richard J. Durbin..................    52
Additional Committee Questions...................................    53
Additional Statements:
    Prepared Statement of Alzheimer's Foundation of America......    75
    Prepared Statement of United Domestic Workers of America,
      American Federation of State, County and Municipal
      Employees (AFSCME), Local 3930.............................    79
    Prepared Statement of USAgainstAlzheimer.....................    80
    2012-2013 Alzheimer's Disease Progress Report: Seeking the
      Earliest Interventions.....................................    82

 
     TAKING A TOLL ON FAMILIES AND THE ECONOMY: THE RISING COST OF
                         ALZHEIMER'S IN AMERICA

                              ----------


                      WEDNESDAY, FEBRUARY 26, 2014

                           U.S. Senate,
    Subcommittee on Labor, Health and Human
     Services, and Education, and Related Agencies,
                               Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 2:03 p.m., in room SD-106, Dirksen
Senate Office Building, Hon. Tom Harkin (chairman) presiding.
    Present: Senators Harkin, Mikulski, Moran, Cochran, Shelby,
Alexander, and Kirk.


                opening statement of senator tom harkin


    Senator Harkin. The Senate Appropriations Subcommittee on
Labor, Health, Human Services, Education, and Related Agencies
will please come to order.
    Today's hearing is the sixth that this subcommittee has
held since 2000 focusing on Alzheimer's disease, the burden of
the disease, the state of the research, and the challenges
faced by caregivers. Going back many years, we have heard
predictions from experts about the far-reaching consequences
this disease will have on the quality of life for American
families and the burden it will place on our economy in the
years ahead.
    Last April, a major study predicted that these consequences
will be far greater than anyone even previously imagined. We
will hear from the author of that study today on our second
panel. I won't steal his thunder, but I do note that this study
commanded the attention of the Nation and particularly this
subcommittee.
    There are few Americans whose life hasn't been touched in
some way by Alzheimer's disease, whether through a family
member or a friend. It is the most common form of dementia
among older Americans, and its risk increases with increasing
age. For those living with the disease, its ravages get worse
over time, as does the burden on their families and on society.
    The number of Americans living with Alzheimer's has doubled
since 1980, and the growth will almost certainly accelerate as
the baby boom generation continues to retire in the future.
    The Federal Government's involvement in Alzheimer's disease
research began in 1976 when three institutes at the National
Institutes of Health (NIH) invested a total of $3.8 million in
research into the cause of this disease. We now spend
approximately $0.5 billion each year on research into
Alzheimer's disease.
    We have had some successes along the way. But the harsh
reality is that we still do not know how to prevent, reverse,
or definitively diagnose Alzheimer's disease. More research is
desperately and urgently needed.
    This subcommittee has always adhered to a strict policy of
not earmarking money for particular diseases, or definitively
saying what diseases the money has to go to--a good policy.
Instead, we allow the peer-review process to support the most
promising science. However, we were able to provide a $131
million increase for the National Institute on Aging in the
recent fiscal year 2014 Omnibus, again with the expectation
that promising science in Alzheimer's disease will be
supported.
    We have a distinguished panel of experts here today:
Scientists, economists, patients, family members. We also have
quite an audience. Let me welcome representatives of the
Alzheimer's Association, some of you came a long way to be here
today. We thank you for your tireless work to educate Members
of Congress and the press about the need to do more to help you
and your loved ones.
    Also in the audience are students from the University of
Virginia. These young people are spending a day here learning
about budget and appropriations, and we welcome all of you here
also.
    [The information follows:]

    These students were brought here by one of our retired Senate
Appropriators, Galan Fountain, he was the clerk on Agriculture
Subcommittee for a long time. The students with him today are: Abraham
Axler, Andrew Boyer, Luke Handley, William Henagan, Ian Van Der Hoven,
Drew Ricciardone, and Blake Sinyard. I hope you will learn something
today.

    Senator Harkin. On our first panel, of course, we'll hear
from Dr. Francis Collins, the distinguished Director of the
National Institutes of Health, who will discuss the current
state of science and what kinds of research are most likely to
benefit from our appropriations. I would note we are also very
fortunate to have both Dr. Story Landis of the National
Institute of Neurological Disorders and Stroke, and Dr. Richard
Hodes of the National Institute on Aging, also here to answer
questions.
    On the second panel, we'll hear from Dr. Michael Hurd, the
researcher who wrote the landmark RAND study that I mentioned
earlier. And we'll be joined by two individuals personally
impacted by this devastating disease.

                           PREPARED STATEMENT

    Finally, former Congressmen Dennis Moore of Kansas is here
today. As a long-time colleague and friend of his, I was
saddened to learn of his Alzheimer's diagnosis so soon after
his retirement from the House of Representatives. It's no
surprise to anyone who knows him, though, that his first
instinct was to educate others and continue serving the public
through advocacy and education.
    So I look forward to hearing from each of our distinguished
experts.
    [The statement follows:]
                Prepared Statement of Senator Tom Harkin
    Today's hearing is the sixth this subcommittee has held since 2000
focusing on Alzheimer's disease--the burden of this disease, the state
of research, and the challenges faced by caregivers.
    Going back many years, we have heard predictions from experts about
the far-reaching consequences this disease will have on the quality of
life for American families and the burden it will place on our economy
in the years ahead. Last April, a major study predicted that those
consequences will be far greater than anyone previously imagined. We
will hear from the author of that study today, so I won't steal his
thunder now. But I note that this study commanded the attention of the
Nation and, in particular, this subcommittee.
    There are few Americans whose life hasn't been touched in some way
by Alzheimer's disease--whether through a family member or a friend. It
is the most common form of dementia among older Americans, and its risk
increases with increasing age. For those living with the disease, its
ravages get worse over time--as does the burden on society. The number
of Americans living with Alzheimer's has doubled since 1980, and the
growth will almost certainly accelerate as the Baby Boom generation
continues to enter its senior years.
    The Federal Government's involvement in Alzheimer's disease
research began in 1976 when three Institutes at the National Institutes
of Health invested a total of $3.8 million in research into the cause
of the disease. We now spend approximately half a billion dollars each
year on research into Alzheimer's disease.
    We've had successes along the way. But the harsh reality is that we
still do not know how to prevent, reverse, or definitively diagnose
Alzheimer's disease. More research is desperately and urgently needed.
    This subcommittee has always adhered to a strict policy of not
earmarking money for particular diseases, instead allowing the peer-
review process to support the most promising science. However, we were
able to provide $131 million increase for the National Institute on
Aging in the recent fiscal year 2014 Omnibus, with the expectation that
promising science in Alzheimer's disease will be supported.
    We have a distinguished panel of experts here today: Scientists,
economists, patients, and family members. We also have quite an
audience. Let me welcome representatives of the Alzheimer's
Association, some of whom came a long way to be here today. We thank
you all for your tireless work to educate members of Congress and the
press about the need to do more to help you and your loved ones. Also
in the audience are students from the University of Virginia. These
young people are spending a day here learning about budget and
appropriations. We welcome all of you.
    First, we'll hear from Dr. Francis Collins, the distinguished
director of the National Institutes of Health, who will discuss the
current state of science and what kinds of research are the most likely
to benefit from the fiscal year 2014 appropriation.
    I would also note that we are very fortunate to have both Dr. Story
Landis of the National Institute for Neurological Disorders and Stroke,
and Dr. Richard Hodes of the National Institute on Aging, here to
answer questions.
    On the second panel, we'll hear from Dr. Michael Hurd, the
researcher who wrote the landmark Rand study that I mentioned earlier.
He will explain the projected growth in the disease and the impact on
our economy.
    We are also joined by two individuals who are personally impacted
by this devastating disease. Mr. Seth Rogen is an accomplished actor,
writer, and producer who is known for his talent in dealing with some
very serious topics through humor, including non-Hodgkin's lymphoma in
the film ``50/50,'' and the challenges of suddenly and unexpectedly
becoming a father in the movie ``Knocked Up.'' And, yes, for the
record, I believe this is the first time the words ``knocked up'' have
been uttered in a congressional hearing! More importantly for our
purposes today, Mr. Rogen is a tireless and effective champion for the
Alzheimer's Association. He will speak about his experience marrying
into a family with a history of Alzheimer's disease, and supporting a
spouse in caregiving.
    Finally, former Congressman Dennis Moore of Kansas is here, today.
As a long-time colleague and friend of the Congressman, I was saddened
to learn of his Alzheimer's diagnosis so soon after his retirement from
the House of Representatives. It is no surprise to anyone who knows
him, though, that his first instinct was to educate others and continue
serving the public through advocacy and education. He is an
inspiration.
    I look forward to hearing from each of these distinguished experts.
Before we turn to the first panel, I'll yield the microphone to Senator
Moran for his opening statement.

    Senator Harkin. Before we turn to the first panel, I'll
yield to Senator Moran for his opening statement.

                    STATEMENT OF SENATOR JERRY MORAN

    Senator Moran. Mr. Chairman, thank you very much. I'll make
my remarks relatively brief because I would not want to detain
or delay the testimony of our distinguished experts. But I very
much appreciate what you just said, and I appreciate your
willingness to conduct this hearing on Alzheimer's disease. In
my view, this could be the defining disease of our generation.
    I'm pleased, as you indicated, to have former Congressman,
Kansas Congressman Dennis Moore testify on his experience with
living with Alzheimer's. I appreciate Dennis as a friend, and I
also appreciate his desire to take his own difficult challenges
and focus them in helping other individuals and families
struggling with this horrific disease. He has used the years
since his diagnosis to advocate for those living with the
disease. And in Dennis's words, ``We need to find a cure, like
next week.'' I could not agree more.
    Mr. Chairman, every 68 seconds, someone in America develops
Alzheimer's disease, a devastating, irreversible brain disease
that slowly destroys an individual's cognitive functioning,
including memory and thought. Alzheimer's currently affects
more than 5.2 million people in the United States and more than
44 million worldwide, according to the Alzheimer's Disease
International.
    As our population ages, the number of people diagnosed with
Alzheimer's after the age of 65 will double every 5 years,
while the number of individuals 85 years and older with the
disease will triple by 2050. Already, Alzheimer's is the sixth
leading cause of death in the United States, and there is
currently no cure, no diagnostic test, no treatment. With the
baby boomer generation aging, Alzheimer's disease becomes more
prevalent and the need to confront the pending healthcare
crisis has become ever more urgent.
    As you indicated, the study by RAND Corporation stated the
cost of dementia is projected to double over the next 30 years,
surpassing healthcare expenses for both heart disease and
cancer. Alzheimer's disease has become a disease to define a
generation, but if we focus our priorities on our research
capacity, it does not need to continue to be an inevitable part
of the aging process.
    For every $270 that Medicare and Medicaid spends caring for
individuals with Alzheimer's, the Federal Government only
spends $1 on Alzheimer's research. In fiscal year 2014, the
Omnibus Appropriation Bill provided for an increase of $100
million for Alzheimer's research. And I appreciate working with
you to accomplish that goal.
    But without a way to prevent, cure, or effectively treat
Alzheimer's, it will be difficult, if not impossible, to rein
in our Nation's healthcare costs. In this subcommittee and in
the full committee, you've often heard me say that I really
appreciate dealing with the issue of healthcare and health
research.
    Health research is an opportunity for those who are the
most fiscally conservative and those who are the most caring
and compassionate to come together, because we can save
tremendous amounts of money and we can improve people's lives
by doing so. It's an opportunity for all of us to work together
to find a solution.
    One study has found that a breakthrough against Alzheimer's
that delays the onset of the disease by 5 years would mean a
total savings of $447 billion by 2050. Now is the time that, as
a nation, that we fully commit to defeating one of the greatest
threats to our health of Americans and the financial wellbeing
of our country.
    1962, President Kennedy called the Nation to action to
reach the moon by the end of that decade. We need to commit
ourselves to the goal of advancing Alzheimer's research with
the same ambition and urgency. Over the next decade, we must
strive to achieve not only an effective treatment, but a cure
for Alzheimer's. Alzheimer's is, as I say, the defining
challenge of our generation. We need to find a cure, like next
week.
    The gift that we all could provide, every American and
every American family, is a special gift. It's called the gift
of hope.
    Mr. Chairman, thank you very much.
    Senator Harkin. Thank you, Senator Moran.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES


                     National Institutes of Health

    Senator Harkin. Now we welcome our first panel. Dr. Francis
Collins, the Director of the National Institutes of Health,
overseeing the work of the largest biomedical research entity
in the world that spans the spectrum from basic to clinical
research.
    Dr. Collins is a physician geneticist noted for his
landmark discoveries of disease genes, his leadership of the
Human Genome Project, which he started in 1993, culminated in
April 2003. He continued on in that capacity until 2008, and is
now the Director of the National Institutes of Health.
    He is an elected member of the Institute of Medicine and
the National Academy of Sciences. He was awarded the
Presidential Medal of Freedom in November 2007, and received
the National Medal of Science in 2009.
    I also want to welcome Dr. Richard Hodes, the Director of
the National Institute of Aging. He has held this position
since 1993. This is our primary Federal agency supporting and
conducting Alzheimer's disease research. As director, Dr. Hodes
oversees studies of the basic, clinical, epidemiological, and
social aspects of aging.
    And Dr. Story Landis, the Director of the National
Institute of Neurological Disorders and Stroke (NINDS); she has
served as its director since 2003. NINDS, as we call it,
supports and conducts basic translational and clinical research
on the normal and diseased brain system.
    So we welcome you all here. Dr. Collins, again, thank you
for your leadership through all these years, both first for the
human genome project and now for the entire National Institutes
of Health. Dr. Collins, welcome, and please proceed.
STATEMENT OF FRANCIS S. COLLINS, M.D., Ph.D., DIRECTOR
ACCOMPANIED BY:
        RICHARD J. HODES, M.D., DIRECTOR, NATIONAL INSTITUTE ON AGING
        STORY C. LANDIS, Ph.D., DIRECTOR, NATIONAL INSTITUTE OF
            NEUROLOGICAL DISORDERS AND STROKE
    Dr. Collins. Thank you. Good afternoon, Mr. Chairman, and
members of the subcommittee. As always, it's a great honor to
appear before you, along with my two distinguished colleagues.
We're here to discuss the latest research into Alzheimer's
disease and related dementias. Before getting into the science,
I would like to thank you for the recent fiscal year 2014
Omnibus appropriation for NIH.
    This subcommittee came together in a bipartisan way to
reverse the deeply troubling downward spiral of support that
NIH has found costing us about 25 percent of our purchasing
power for research over the last 10 years. While difficult
tradeoffs did not ultimately make it possible in fiscal year
2014 to completely reverse the devastating effects of the
fiscal year 2013 sequester, we are gratified that NIH was at
least able to turn that corner.

                    THE GROWING PUBLIC HEALTH CRISIS

    Let me begin my report on the scientific challenges and
promises that we face in Alzheimer's by underscoring that all
of the work that I'm going to discuss is really about helping
patients and their loved ones. That's what we are committed to,
and we know you are, too.
    One of the most famous of those patients is country music
star Glenn Campbell. Along with a number of you, I was thrilled
to be on hand last spring when Glenn was honored at the
Alzheimer's Association gala. There's a photo of him and me
with an autographed guitar pick that he gave me, which is my
prized possession, since I'm a musician also. To see his great
talents, a national treasure, really, so compromised by this
devastating disease is a reminder of just how much is at stake.
    We've heard the sobering statistics, and they've been
already cited in opening statements by Senator Harkin and
Senator Moran, about the wave of diseases that will break over
the United States as the baby boom generation ages. Already
about 5 million Americans have been diagnosed with Alzheimer's
disease, and hundreds of thousands more affected with other
types of dementia.
    Without new scientific breakthroughs, those numbers will
continue to rise, along with the terrible toll on our Nation's
health and its economy that this disease creates. As you've
mentioned already, the Alzheimer's Association estimates that
our Nation is currently spending more than $200 billion a year
on care of people with Alzheimer's. And those costs are
projected to soar to $1.2 trillion annually by 2050.
    To put this into context, consider how much our Nation is
spending on medical research. NIH's budget was $29.1 billion in
fiscal year 2013, with $504 million of that devoted to
Alzheimer's disease research. We are thrilled that the fiscal
year 2014 Omnibus includes an additional $100 million for
research on diseases of aging, including Alzheimer's disease.
But as you can see, the investment pales in comparisons to the
cost.

                          REVVING UP RESEARCH

    In our effort to find ways to prevent, delay, or treat
Alzheimer's and other dementias, we are bringing to bear all
possible technologies, from genomics to imaging to big data
tools. But this task is immense. There are a great many things
we still don't know about how the normal brain functions, let
alone a brain with Alzheimer's.
    In fact, this month's National Geographic provides a
glimpse at what NIH-funded researchers are doing to explore
what's been called biology's last frontier, the human brain.
And I couldn't help but notice Scientific American, just on the
newsstands, has the brain on its cover also for the current
issue.
    As you know, NIH is leading the initiative called Brain
Research Through Advancing Innovative Neurotechnologies. That's
an acronym, B-R-A-I-N. And we are grateful for the
subcommittee's support for this pioneering venture in the
fiscal year 2014 Omnibus. The BRAIN initiative, which the
President has called ``the next great American project,'' will
create tools capable of examining the activity of the brain's
billions of nerve cells, networks, and pathways, in real time.
That's sure to be of tremendous value to researchers who are
working on autism, schizophrenia, epilepsy, traumatic brain
injury, depression, Parkinson's disease, and, yes, all forms of
dementia, including Alzheimer's.
    Let me tell you of one recent finding in brain science
that's generated a lot of excitement. It involves a protein
called tau, T-A-U. This is one of the major culprits in
Alzheimer's disease. The other one is amyloid. To give you a
better idea about how tau affects the brain, I'd like to show
you this short video, and I'll explain what you're looking at.
    In normal brain cells, this tau protein that you see here
stabilizes structures that are called microtubules and that are
involved in internal transport. That's what you see happening
here with this amazing machine inside the cell. But in
Alzheimer's, the tau separates from those microtubules, causing
them to fall apart. Strands of this tau protein then combine to
form tangles within the neuron, disabling the transport system
and destroying the cell, ultimately, as you see in this
animation. Neurons in certain parts of the brain disconnect
from each other, and eventually they die, causing memory loss.
    The effect on the brain? The brain shrinks and begins to
lose function, showing you here what happens in advanced
Alzheimer's disease, as the brain's substance is gradually
shrunken away by the loss of brain cells.
    Now, one of the exciting findings recently is we've
discovered that this tau protein, which we used to think was
just inside cells, and therefore kind of inaccessible, that
it's actually transferred from neuron to neuron, almost like an
infection inside the brain. That may sound a little scary, but
for us it means opportunities for therapy. Proteins that spend
their whole existence inside cells, they're hard to attack. But
if we can find a way to prevent that cell-to-cell transmission,
perhaps by blocking tau with an antibody, we might be able to
stop Alzheimer's in its tracks.
    Still, new drugs won't do a whole lot of good unless we can
identify accurately those who might benefit from them. To do
that, we need better ways to diagnose Alzheimer's disease and
to do so as early as possible. Until recently, we could only
conclusively diagnose Alzheimer's after someone had died. This
involved examining slides of brain tissue, like you see here,
for the classic signs of Alzheimer's disease, amyloid plaques
and tangles, neurofibrillary tangles made up of tau.

                             BRAIN IMAGING

    But now, thanks to recent advances in imaging technology,
we can detect signs of Alzheimer's inside living brains. What
you see here are PET scans of two living people. On the top, an
Alzheimer's patient whose brain lights up with markers for both
tau on the left and amyloid on the right. And on the bottom,
you see a normal brain. Quite a difference.
    Importantly, these scans are able to detect deposits of tau
and amyloid years before the onset of symptoms. That should
improve our ability to diagnose and, hopefully, treat
Alzheimer's at a much earlier stage before so many brain cells
have been lost.
    It may also be possible to use these scans or other
biochemical measures in blood or spinal fluid to see if a new
therapy is working even before it has an impact on the course
of memory loss. Those kinds of predictive measures are called
biomarkers, and one of our top priorities is to find and
validate those kinds of biomarkers for clinical use so we'll
know if treatments are working, as quickly as possible.
    This leads me to the crucial issue of clinical trials.
Until a couple of years ago, we focused primarily on trying to
treat people with unmistakable symptoms of advanced
Alzheimer's, those who had already lost many of their brain
cells. The results, I'm sorry to say, have been almost entirely
discouraging. But today, we are focused on earlier
interventions. So many of our newest clinical trials are
actually looking at pre-symptomatic patients who are at high
risk, but don't yet show symptoms.
    One of these is a 5-year clinical trial to see if an
antibody treatment aimed at amyloid can prevent cognitive
decline by starting a treatment before any symptoms appear. In
a unique situation, we're testing this among members of a very
large family in Colombia, as well as some U.S. patients, who
share a dominantly inherited genetic mutation that causes
Alzheimer's at about age 45 and places those individuals at
extremely high risk.
    A second study, the Anti-Amyloid Treatment in Asymptomatic
Alzheimer's, also just called A4 because that's easier to say,
this will test another antibody in 1,000 volunteers aged 65 to
85. These individuals do not yet have any symptoms of
Alzheimer's, but by PET scans they're found to have sufficient
amyloid in their brain to be considered at risk, like the
person in the middle here. This is somebody with completely
normal function, but there's a lot of amyloid there. Is that
somebody who will go on to Alzheimer's? Is this the moment to
intervene? This is a great opportunity, again, to try
therapeutics before there has been major damage done to the
brain.
    All of these studies will hinge upon validated biomarkers,
as I mentioned a minute ago, which is why I'm especially
excited to announce the Accelerating Medicines Partnership, or
A-M-P, AMP, earlier this month. AMP is an unprecedented
collaboration between NIH and 10 pharmaceutical firms and will
accelerate identification and testing of drug targets for
Alzheimer's disease, diabetes, rheumatoid arthritis, and Lupus.
    About $230 million will be invested over 5 years, with NIH
and industry contributing equally; we both have skin in the
game. For Alzheimer's disease, AMP will incorporate an expanded
set of biomarkers into four ongoing trials designed to delay or
prevent disease, and then evaluate those for effectiveness.
Another part of the project will develop detailed maps of
molecular networks in the Alzheimer's brain, potentially
pointing to new therapeutic targets.

                  EXPANDED FUNDING, EXPANDED DISCOVERY

    And empowered by the $100 million fiscal year 2014 budget
increase for research on diseases of aging, NIH will be able to
make major investments in four cutting-edge areas of dementia
research that we would otherwise not have been able to pursue:
Genetic analysis, optogenetics, stem cells, and translational
centers.
    Similarly, we will now be able to fund a significant number
of investigator-initiated research grants, or RO1s, that
otherwise would not have made the pay line and would have gone
unsupported.
    So, Mr. Chairman and members of the subcommittee, I began
talking about people with Alzheimer's disease. I'd like to
close with a tribute to another deeply affected group, and
represented, I'm sure, by many in this room: The people who
care for their loved ones as they slip into those deepening
shadows of Alzheimer's and dementia.
    One such caregiver is Meryl Comer, friend of mine, a former
TV newscaster, who has cared full time for her husband, Harvey
Gralnick, in their home for nearly 20 years. Harvey was a
leading investigator at NIH until he began showing signs of
confusion in his late 50s.
    Just last week, Meryl shared with me these lines from a
book that she's working on about her experience, entitled,
poignantly, Slow Dancing with a Stranger. Her words: ``As I
write these words, a faint glow of light fills the room I share
with Harvey. He's always present even though he is absent. The
person I knew is lost, but not gone.'' So heartbreaking and so
true.

                           PREPARED STATEMENT

    What Harvey has suffered, what Meryl has suffered is what
inspires all of us in Alzheimer's research to fight back
against this insidious disease as vigorously and swiftly as
possible. That is our commitment, and there is no time to
waste.
    On behalf of my colleagues, thank you for this opportunity.
We look forward to your questions.
    [The statement follows:]
Prepared Statement of Dr. Francis S. Collins, Dr. Richard J. Hodes, and

                          Dr. Story C. Landis
    Good afternoon, Mr. Chairman and distinguished members of the
committee. I am Francis S. Collins, M.D., Ph.D., the Director of the
National Institutes of Health (NIH). I have with me Story C. Landis,
Ph.D., Director of the National Institute of Neurological Disorders and
Stroke (NINDS), and Richard J. Hodes, M.D., Director of the National
Institute on Aging (NIA). It is an honor to be here today to discuss
NIH's efforts to stem the rising tide of Alzheimer's disease, a
devastating condition and a public health issue of increasing relevance
and urgency, both in the United States and globally.
    First, however, I would like to thank you, Mr. Chairman, and
Ranking Member Moran, as well as your colleagues on the committee, for
your unflagging championship of NIH's research mission, especially our
research on Alzheimer's disease. I would particularly like to
acknowledge the significant increase in funding that you have provided
to NIH for fiscal year 2014, in order to bolster our support for
research on aging. I am happy to share with you some of our plans for
these additional funds, as well as some exciting recent scientific
discoveries and new initiatives.
                    the growing public health crisis
    As all of us are only too well aware, Alzheimer's disease is a
currently irreversible, progressive brain disease that slowly destroys
memory and thinking skills and eventually even the ability to carry out
the simplest tasks of daily living. In most people with Alzheimer's,
symptoms first appear after age 60. While Alzheimer's disease is the
most common cause of dementia among older people, other forms exist,
including frontotemporal dementia, Lewy body dementia, and mixed and
vascular dementias. Although treatment can help manage symptoms in some
people, there is currently no cure for these devastating diseases.
    As many as 5 million people age 65 and older suffer from
Alzheimer's disease in the United States alone, and we expect these
numbers to increase exponentially as the U.S. population continues to
age. Globally, the statistics are truly dire: Results of a recent meta-
analysis suggest that 35.6 million people lived with dementia worldwide
in 2010, with numbers expected to double almost every 20 years, to 65.7
million in 2030 and 115.4 million in 2050.
    This disease is not just a burden on our health; it is also a
burden on our economy. Recently, NIH-supported economists calculated
that the costs in 2010 to the U.S. healthcare and long-term care
systems for caring for people with Alzheimer's disease were between
$159 billion and $215 billion, depending on how caregiver costs were
assessed. The researchers estimated direct costs of dementia care
purchased in the market in 2010 at $109 billion. To place that figure
in context, that same year, direct health costs for heart disease and
cancer were estimated at $102 billion and $77 billion, respectively.
And again, unless effective interventions are developed, those costs
will rise dramatically with the increase in the numbers of senior
citizens in coming decades.
                       an explosion of knowledge
    The good news, in the face of these grim statistics, is that we
have made tremendous strides in our understanding of the basic
mechanisms of Alzheimer's disease within the last 5 years, and this new
understanding has led to entirely new research paradigms: Both for
studying the disease in the laboratory and managing it in the clinic.
    The first set of discoveries I'd like to discuss have to do with
the genetics of Alzheimer's disease. Until 2009, only one genetic
variant, APOE e4, had been shown to increase the risk of late-onset
Alzheimer's disease. However, with the advent of genome wide
association studies (GWAS) and other high throughput technologies, the
list of known gene risk factors grew substantially over the next few
years, and in 2013, the largest GWAS ever conducted identified a total
of 11 genetic risk factors. The research conducted by the International
Genomic Alzheimer's Project--a collaborative, international study
supported in part by the NIH--strengthens evidence about the
involvement of particular pathways in the disease, such as
inflammation, lipid metabolism, and amyloid deposition, and also points
to entirely new molecular pathways that were not known to be involved.
    In the clinical arena, researchers--supported by a compelling body
of NIH-supported research--have realized that the most effective way to
treat and prevent Alzheimer's disease is to attack it early, before
symptoms begin. Investigators discovered that higher amounts of brain
beta-amyloid, the toxic protein that clogs the brains of Alzheimer's
patients and is associated with memory loss and other symptoms, is
related to an increased risk of developing dementia over time and to
loss of brain volume and subtle declines in cognitive abilities. These
findings suggest that brain beta-amyloid may in fact be a preclinical
sign of disease even among individuals who appear cognitively normal.
    In parallel, NIH-supported investigators with the Alzheimer's
Disease Neuroimaging Initiative (ADNI) established a method and
standards for testing levels of beta-amyloid and tau, another known
biomarker for Alzheimer's disease, in the cerebrospinal fluid (CSF).
They correlated levels of these proteins in the CSF with changes in
cognition over time and determined that changes in these two protein
levels in the CSF may precede the onset of the disease.
    In 2011, these findings made possible the first revision of the
clinical diagnostic criteria for Alzheimer's disease in 27 years
through a joint effort of the NIA and the Alzheimer's Association.
Unlike the previous criteria, the updated criteria cover the disease as
it gradually progresses over many years, from the earliest preclinical,
pre-symptomatic phase through mild cognitive impairment (MCI) to
advanced dementia. The new guidelines also address the use of imaging
and biomarkers to determine whether changes in the brain and body
fluids are due to Alzheimer's. A separate update addresses diagnosis at
autopsy, to help neuropathologists characterize Alzheimer's-related
brain changes at death in people who have been diagnosed with dementia
and those who have not yet shown clinical symptoms, taking into account
that the disease process may begin a decade or two before outward signs
like memory loss appear.
    Recognizing the devastating impact of Alzheimer's disease and
Alzheimer's Disease-Related Dementias, or ADRDs, on patients and
families, and also recognizing that the time is right--from both a
scientific and a public health standpoint--to move aggressively toward
the development of new and effective treatments for Alzheimer's and
ADRDs, President Obama signed the National Alzheimer's Project Act
(NAPA) into law on January 4, 2011. NAPA requires the HHS Secretary to:
  --Create and maintain an integrated national plan to overcome
        Alzheimer's disease and related dementias;
  --Coordinate research and services across all Federal agencies;
  --Accelerate the development of treatments that prevent, halt, or
        reverse the disease;
  --Improve early diagnosis and coordination of care and treatment of
        the disease;
  --Improve outcomes for ethnic and racial minority populations at
        higher risk;
  --Create an Advisory Council to review and comment on the national
        plan and its implementation;
  --Coordinate with international bodies to fight Alzheimer's disease
        globally.
    Under NAPA, the first National Plan to Address Alzheimer's Disease
(National Plan) was released on May 15, 2012, was subsequently updated
in June 2013, and will continue to be updated annually.
    In response to guidance from NAPA and the National Plan, NIA
convened the Alzheimer's Research Summit 2012: Path to Treatment and
Prevention. An international group of some 500 researchers, clinicians
and members of the broader Alzheimer's community contributed actively
to the Summit process through extensive input and discussion during the
course of the meeting. As a result of recommendations from the Summit,
NIH issued several solicitations for research on topics including the
discovery of basic molecular processes underlying Alzheimer's disease
and drug development and testing. Seven groundbreaking studies, ranging
from research on the most basic underpinnings of the disease to early-
stage clinical trials of promising agents, are now underway.
    In addition, in May 2013, as part of the National Plan, NINDS
together with NIA held the workshop ``Alzheimer's Disease-Related
Dementias: Research Challenges and Opportunities.'' An international
group of experts developed prioritized research recommendations to
address ADRDs, including frontotemporal, Lewy body, mixed, and vascular
dementias, as well as clinical diagnosis and health disparities in
ADRDs. These recommendations were revised based upon public discussion
during the lively two-day conference, and in February, the Advisory
Council on Alzheimer's Research, Care, and Services created under NAPA
recommended that they be added to the National Plan. NINDS has already
begun implementing these recommendations by using a high program
priority funding process to support investigator-initiated grants on
frontotemporal dementia and the vascular contributions to dementia.
                          revving up research
    Research in Alzheimer's disease at NIH today runs the gamut from
very basic neuroscience research to cutting-edge clinical trials
designed to prevent or treat the disease. In the basic science arena, a
major new program that has just begun this year is the Brain Research
through Advancing Innovative Neurotechnologies (BRAIN) Initiative--
referred to by President Obama as the ``next Great American Project''.
NIH is a leading member of this pioneering new venture, and has issued
several research solicitations in the past 2 months that will enable us
to develop a deeper understanding of brain function through the
creation of new tools capable of examining the activity of millions of
nerve cells, networks, and pathways in real time. By measuring activity
at the scale of circuits and networks in living organisms, we can begin
to translate data into models that will decode sensory experience,
motor planning, and, potentially, even memory, emotion, and thought. We
believe that successful completion of the BRAIN Initiative will
revolutionize the field of neuroscience, providing a foundational
platform for major advances in Alzheimer's and other brain diseases.
    Another major current opportunity lies in the work of the
Alzheimer's Disease Sequencing Project (ADSP), a program supporting
large scale DNA analysis for the Alzheimer's disease research
community. The ADSP is a collaboration between NIA-funded geneticists
and the National Human Genome Research Institute Large-Scale Sequencing
Program. Goals of the program are to identify new genes contributing to
increased risk of and protection from the disease; to provide insight
as to why individuals with known genetic risk factors escape the
disease; and to identify potential avenues for therapeutic and
preventive approaches. Last December, NIH announced the availability of
the first batch of genome sequence data from the ADSP, including whole
genome sequence (WGS) data from 410 individuals in 89 families.
Researchers can access the sequence data at dbGaP (http://
www.ncbi.nlm.nih.gov/gap) or the National Institute on Aging Genetics
of Alzheimer's Disease Data Storage Site (NIAGADS), https://
www.niagads.org/.
    Still another example of how NIH-supported research is accelerating
scientific discovery, with the potential for tremendous gains in the
area of Alzheimer's disease, is in the area of stem cells. Induced
pluripotent stem (iPS) cell technology is revolutionizing the way we
study disease, and holds the promise of dramatic advances in treatment.
iPS cells are patient-derived cells, typically from skin or blood, that
scientists can reprogram back to an embryonic stem cell-like state.
These cells can then be induced to turn on specific sets of genes to
differentiate into a variety of cell types, including neurons. For
Alzheimer's disease, it has been possible to show abnormalities in
amyloid metabolism in this ``disease in a dish'' model, opening the
door to a new method to screen drug compounds for possible efficacy.
    A seminal finding that has recently generated a lot of excitement
is the discovery that the protein, tau, which appears to be in part
responsible for the cognitive decline in Alzheimer's patients, may
spread from neuron to neuron. This means that if researchers could find
a way to prevent cell-to-cell transmission, perhaps by blocking tau
with an antibody, the disease process could be halted. The problem was
that until recently we had no way of visualizing what was happening
with tau inside the living brain, making it difficult to assess the
efficacy of treatment on that particular molecule. However, last fall
researchers reported that they had developed a new class of imaging
agents, termed PBBs, that bind to tau deposits in transgenic mice and
in human subjects with normal cognition, Alzheimer's disease, or a
corticobasal syndrome. The ability to visualize both beta-amyloid and
tau in the living organism will enable us to evaluate the effect of new
treatments more rapidly and efficiently than ever before.
    With respect to new treatments for Alzheimer's disease, as I noted
before, the paradigm has really shifted in recent years, from an
emphasis on treatment of individuals with symptomatic disease to
primary prevention among individuals at risk. This is not to say that
we have forgotten those patients whose disease has advanced; NIH
currently supports clinical trials of interventions for agitation,
disruption, depression, and other troubling symptoms of Alzheimer's in
affected individuals.
    Vascular contributions to dementia are especially common and
highlight the complex relationships among various types of dementia.
The 7 million U.S. stroke survivors and 13 million people who have had
``silent strokes'' have an increased likelihood of cognitive problems.
Brain vascular problems that cause stroke are associated with
Alzheimer's disease in multiple ways. For example, signs that a stroke
has occurred are often found in the brains of Alzheimer's patients, and
beta-amyloid, a key protein in Alzheimer's pathology, may stimulate the
formation of blood clots, which can cause stroke. The Reasons for
Geographic and Racial Differences in Stroke (REGARDS) study, which is
following more than 30,000 people, is one of several epidemiological
studies that demonstrate that high blood pressure and other known risk
factors for stroke increase the risk of cognitive problems, even among
people who have never had a stroke. Because reducing blood pressure and
other cardiovascular risk factors might have an immediate impact on
dementia, NINDS and NIA are funding a study to test whether an
aggressive treatment program to reduce systolic blood pressure lower
than the currently recommended goal also reduces age-related cognitive
decline. This is part of a large, multi-center trial funded by NHLBI
and NIDDK on the effects of this treatment on cardiovascular and kidney
disease.
    However, many of our newest clinical trials focus on
presymptomatic, at-risk patients. New studies include:
  --A 5-year clinical trial to determine if an antibody treatment,
        crenezumab, designed to bind to and possibly clear away
        abnormal amounts of amyloid protein in the brains of people
        with Alzheimer's, can prevent decline in cognitive function.
        Crenezumab will be tested among members of a unique and large
        family population in Colombia sharing a genetic mutation known
        to cause observable signs of Alzheimer's disease at around age
        45, along with a smaller number of U.S. participants ages 30
        and older.
  --The A4 (Anti-Amyloid Treatment in Asymptomatic Alzheimer's) Trial
        which will test the drug solanezumab in 1,000 cognitively
        normal volunteers, age 65 to 85, who have enough of the amyloid
        protein in the brain to put them at risk for developing
        Alzheimer's, but do not show clinical symptoms of the disease.
  --The Dominantly Inherited Alzheimer's Network Therapeutic Trials
        Unit, which will study the effects of different treatments
        among individuals who are at high genetic risk for developing
        the disease. In 2014, the first DIAN-TU trial, a comparison of
        two monoclonal antibodies--gantenerumab and solanezumab--with
        placebo will begin.
    Each of these studies will rely on the availability of validated
biomarkers of disease. Identification and characterization of
biomarkers and targets for intervention are the primary goals of the
Accelerating Medicines Partnership (AMP), just announced in February
2014. With project management by the Foundation for NIH (FNIH), ten
pharmaceutical companies will collaborate with NIH. All data will be
made publicly available, and NIH and industry will share in the $230
million cost over 5 years for the first projects: Alzheimer's disease,
type 2 diabetes, and the autoimmune disorders rheumatoid arthritis and
systemic lupus erythematosus. For Alzheimer's disease, AMP resources
will be used to incorporate an expanded set of biomarkers into four
ongoing trials designed to delay or prevent disease, and then evaluate
which ones are most effective. AMP resources will also support large-
scale, systems biology analyses of brain tissue samples from people
with Alzheimer's disease to validate biological targets that play key
roles in disease progression, in order to increase understanding of
molecular networks involved in the disease and identify new potential
therapeutic targets. AMP represents an unprecedented model for pre-
competitive collaboration that should substantially accelerate the
ability to identify the next generation of drug targets and biomarkers.
                  expanded funding, expanded discovery
    On behalf the biomedical research community, whose scientists have
been under stress as NIH purchasing power over the last decade has
declined due to inflationary effects, I would like to acknowledge the
fiscal year 2014 funding increase with which NIH has been entrusted for
supporting new research on aging, including Alzheimer's disease. The
addition of these new funds to our base appropriation will enable us to
plan carefully for their use, consistent with funding the best peer-
reviewed science and the priorities established at the Alzheimer's
Summit and 2013 ADRD Workshop.
    Several fiscal year 2014 initiatives can be mentioned that we plan
to support with this increased base. First, these funds will facilitate
analysis of the DNA sequences generated through the ADSP. Second, we
are soliciting research on the use of iPS and other reprogrammed human
cells specifically for aging and Alzheimer's disease. Also, researchers
will study the function and activity of individual cells in the brain
in animal models by turning functions of those cells on and off using--
simply--light. Remarkably, the technology has advanced to the point
where we can safely introduce tiny lasers and light-sensitive proteins
into the brains of mice and rats. When the laser is remotely activated,
the proteins respond by turning cells on and off, enabling us to track
the cell's function. This technology--known as optogenetics--is being
used in animal models of Alzheimer's disease to provide information
that will help us to understand functions of the normal as well as the
Alzheimer's brain.
    This concludes my testimony. I am happy to respond to your
questions.

    Senator Harkin. Thank you very much, Dr. Collins, for a
very lucid presentation. I must say when you were talking about
that BRAIN initiative, I was driving in to work late one day.
It must have been a Friday or a Monday if I was coming late.
And I heard you on the Diane Rehm Show talking about that. And
once again, I say this with all respect, you're one of the
unique individuals who can take very complicated and hard-to-
understand scientific processes and research and put it in
language that people understand. And I want to thank you for
that. Because I thought what you said on that show just brought
it home to the average person who just doesn't understand a lot
of what this research is involved with.
    So thank you very much for that. And again I compliment you
for that ability.
    We'll start a round of 5-minute questions.

                        CAN WE PREVENT DEMENTIA?

    Dr. Collins, this may be a simplistic question after your
presentation. But I see all kinds of claims about what people
can do to prevent Alzheimer's. Well, let's see. There are brain
games for sale. There are articles telling seniors to do a
crossword puzzle every day, Sudoku also. There are Web sites
suggesting supplements of Ginkgo Biloba or Vitamin E or B12.
There may be others, too.
    What does the research community know about these claims?
What are the best things that individuals can do right now to
lower their risk of dementia or Alzheimer's disease?
    Dr. Collins. Well, you're right that those are questions on
many people's minds, and NIH has funded a lot of research in
that area. I'm going to turn to my colleague Dr. Hodes to
summarize what we have learned.
    Dr. Hodes. Thank you for the very important question. You
know, all of us have to make lifestyle choices every day.
There's no such thing as not making a choice. We do by our
actions. And there's no question that general issues of health,
that exercise, diet are important in many aspects and they
correlate to risk factors for Alzheimer's disease.
    So we know that having high blood pressure or inactivity or
overweight are associated with increased risk of Alzheimer's
disease. But the critical question you asked--Do we know with
certainty what activity, what exercise, what diet will decrease
the probability of developing Alzheimer's disease?--is a
question being addressed by ongoing research for which we do
not currently have a definitive answer.
    I would emphasize again there's important research going on
in this area. So there were studies looking at the effect of
exercise intervention on individuals before they developed
Alzheimer's, who were at early stages of Alzheimer's. In years
to come, we will have the results of those studies. There's a
major study called LIFE that is looking at exercising folks and
then looking at the impact on their ability to maintain
mobility and also cognitive function.
    There are two studies currently funded by investigators at
the University of Kansas that are looking at either pre-
symptomatic or early symptomatic disease to determine whether
exercise actually changes the course of disease or changes
these brain alterations that we have seen.
    We have the ability now, and Dr. Collins emphasized it, as
we never did before to look at the ability of interventions to
make a difference, not just once people have developed disease.
And then we follow for years to see if their symptoms become
worse. We can look before there's any evidence of clinical
disease, we can use biomarkers, and we can determine whether
exercise or cognitive exercises will affect the course of those
processes.
    We're in the midst of those studies now. In these next
years, we should have the answers. In the meantime, although we
say that research does not have a definitive answer, there are
so many good reasons to be practicing the positive aspects of
lifestyle and choices that you mentioned that we have no
hesitation in recommending those.

           AFRICAN AMERICAN PARTICIPATION IN CLINICAL TRIALS

    Senator Harkin. Thank you, Dr. Hodes.
    Our former Surgeon General, David Satcher, brought up a
very important issue in this past Sunday's Washington Post. He
noted that African Americans are two to three times more likely
to develop Alzheimer's disease than non-Hispanic whites, but
they participate in clinical trials at far lower rates than
other ethnic groups.
    [The information follows:]

    The Washington Post article can be found at: http://
www.washingtonpost.com/opinions/more-african-americans-need-to-
participate-in-clinical-trials/2014/02/21/65c89742-9983-11e3-b931-
0204122c514b_story.html

    Senator Harkin. Now, we all know the shameful history of
the Tuskegee experiments. So the community's level of distrust
is natural, and Dr. Satcher referred to that. Is there anything
NIH can do to inspire more participation by minorities in this
research?
    Dr. Collins. Yes, I read that editorial by Dr. Satcher. It
was indeed compelling and moving, a reminder of how important
it is to focus on health disparities. And that's certainly an
issue for Alzheimer's disease.
    I'll say one thing and then ask Dr. Hodes to say a bit more
about what we're doing now. One of the greatest opportunities
in terms of encouraging minority participation in clinical
trials is if the researchers themselves represent the diversity
of our country. You can see that over and over again. This is a
strong reason why we need to focus on improving and expanding
the diversity of our own biomedical research workforce.
    We have a number of new programs that are quite bold. And
this is a high personal priority for me, to try to see if we
could do a better job of recruiting and maintaining and
mentoring and supporting individuals from under-represented
groups in order to populate those clinical trial workforces
with people who represent our country and would, therefore,
perhaps be more welcoming to the groups that, tentatively right
now, are unsure about whether they want to join up or not.
    Dr. Hodes can tell you what we're already doing in terms of
Alzheimer's trials because all of our centers are engaged in
that.
    Dr. Hodes. We are indeed making great efforts to correct
what you point out, an under-representation of minorities in
clinical studies, in particular, clinical trials. All the
Alzheimer's disease research centers, for example, have
outreach cores. Some of them, for example, one in the city of
Chicago, happen to serve an area where some 90 percent of
individuals are African American. But in all cases, these
outreaches are intended to maximize recruitment.
    We're working actively with CDC (Centers for Disease
Control and Prevention) and former AOA (Administration on
Aging), ACL (Administration for Community Living), the partners
in an exercise that's called ROAR (Recruiting Older Adults for
Research), which overall has attempted to increase the
recruitment of older adults into clinical studies and trials
with a very concrete emphasis on minorities. We have a program
of centers that are particularly focused on minority aging
research and developing methods for enhancing the right liaison
and communication with minority communities to increase their
level of comfort, confidence, and stability as a means to
recruiting them to clinical research.
    Senator Harkin. I appreciate that. I hope you'll do it very
aggressively. The chair of our distinguished appropriations
committee and a distinguished member of this subcommittee was
the first person to bring to this subcommittee's attention, a
long time ago, the disparity in women in terms of research
trials at NIH. So I hope that we've taken a lesson from that
and from what Dr. Satcher said and we really become more
aggressive in including these minorities in these clinical
trials.
    So I thank you very much, and I'll now turn to Senator
Moran.

                      PROGRESS IN THE PAST 5 YEARS

    Senator Moran. Mr. Chairman, thank you. Dr. Collins, thank
you for your testimony. We're honored to have you here.
    You indicated in your testimony several developments and
promising opportunities in research in Alzheimer's. Let me ask
you to put this in kind of a chart as an answer. Where were we
5 years ago compared to today? And are the increases in
knowledge: Are they growing at a faster rate all the time? How
does this look in the progress that's being made or not being
made?
    Dr. Collins. Well, I love the question. Thank you, Senator.
    I think if you go back 10 years, people working in
Alzheimer's disease were pretty darn frustrated. The ability to
understand what are the molecular pathways that have gone awry
in the brain to cause this condition was limited. Our tools,
our technologies were not very good at making that kind of
comprehensive assessment.
    Our clinical trials, largely based upon hunches, were
turning out badly. We had a limited number of ideas about where
to go next.
    In my view, and I've been at NIH for 20 years, the last 5
years have been really quite a dramatic change in that
environment. We have learned, through a variety of approaches,
things that we probably didn't expect would be now in front of
us this soon.
    For instance, what are the hereditary factors that are
involved in this disease? It clearly runs in families. We have
gone from knowing sort of one risk factor for the late onset
type of Alzheimer's disease to now, depending on who you ask,
19 or 20 that we have. And that number is growing. In fact, it
will be growing rapidly this coming year, in part because of
the fiscal year 2014 appropriation, because we're expanding our
ability to do that kind of genetic analysis.
    We have gone from understanding that amyloid was a player
to now understanding a lot more about tau, and to be able to
look at pathways in the brain that are really quite complex,
and point to other sort of nodes in those pathways that are
really important and might be drug-able.
    We have gone from having a few clinical trials focused
largely on advanced cases of Alzheimer's to what you heard
about today, where we, now because we can make the prediction
about high risk, start the treatment earlier. Just like people
have often said, and I'll say it now: If you try to test
statins by waiting until somebody had far-advanced congestive
heart failure, you would assume they don't work because you're
too late.
    Well, likewise, if we want to have a successful treatment
for Alzheimer's, start while there are still lots of brain
cells and see if you can protect them.
    So there's a sense in this community of momentum. And it's
coming from imaging and genomics and clinical studies and
biochemistry and behavior studies. Everything is sort of
coalescing here. So it is the right moment to really try to
provide that extra push. And that's why what's happened in
fiscal year 2014 could not come at a better time. It's momentum
we hope can be sustained. As you know, this kind of science is
not a 100-yard dash. We're engaged in a marathon.
    The other thing about that trajectory you're asking about,
it's on an upward course. But I guarantee you it won't be a
smooth and steady one. It will be herky-jerky, because we'll
have big moments of realization that we've learned something we
didn't expect. And then we'll have big disappointments where a
clinical trial that looked really good, somehow it didn't work.
We've got to go back to the drawing board. It's going to be
jumping around a bit. But it's headed upward.
    And it is my hope and my commitment that, with your help
and with the amazing talent that we have in our U.S. and
worldwide scientific workforce, we are going to tackle and win
this disease battle.
    Senator Moran. I appreciate that answer, and again you used
the word ``hope.'' I always use the word ``hope'' when it comes
to medical research. And what you're suggesting is that there
are reasons to be hopeful.
    Dr. Collins. Yes. I totally support that statement 100
percent.

                 DOWN SYNDROME AND ALZHEIMER'S DISEASE

    Senator Moran. Let me ask about a particular set of people
that we care greatly about. Scientists have discovered that
people with Down syndrome are at increased risk for developing
Alzheimer's disease. By the age of 40, as I understand, almost
everyone with Down syndrome has beta-amyloid deposits in their
brain. Yet only about half of those people who have Down
syndrome ever develop dementia. And even if they do, they
develop plaque.
    So my question is: Is NIH exploring the question of why 50
percent have a different outcome, a different result than the
other 50 percent?
    Dr. Collins. A wonderful question, Senator. I just spoke
this morning to Dr. Guttmacher, who is the Director of the
Child Health Institute, about this very issue. This is another
opportunity perhaps to try to understand this disease in a
group that has such a high risk. And both in terms of
understanding why some develop and some do not, what are the
other modifiers? But also, this could be a great opportunity to
try new therapeutics at the earliest stage before the dementia
has begun to actually take its toll on function.
    There was a workshop which was held specifically on this
topic about Alzheimer's and other dementias in Down syndrome
kids. There's a challenge here in terms of things like the
informed consent. We would want to do whatever we were doing in
a way that's absolutely recognizing the difference in carrying
out research in individuals who may themselves not be in the
best position to give consent. We will depend on their parents.
    But there is intense interest in this, and I would predict,
based on that workshop, that in the course of the next year or
two, there will be in fact new initiatives focused on that very
special population to see what we can learn and see how we can
help.
    Senator Harkin. Thank you. In order, I have here Senator
Mikulski, then Senator Shelby, Cochran, Kirk, and Alexander.
    Senator Mikulski.
    Senator Mikulski. Thank you very much, Mr. Chairman. Thank
you and also Ranking Member Moran for organizing this hearing
on this topic of Alzheimer's. It is very special to me because
my own very dear father died of the consequences of
Alzheimer's, now 25 years ago. So I've been at this a long
time.
    And for many of us, we've had it either in our own families
or people near and dear to us. And of course, there are marquee
names that talk about this--Mrs. Reagan, Justice Sandra Day
O'Connor, and others.
    But really, this is an equal opportunity epidemic. It hits
people at all income levels. And whether you are the President
of the United States, like President Reagan, or a small grocer
businessman like my father, or like the men and women out here
in the audience who wear the purple sash, they know this
tremendous impact on family life, the family budget, and
ultimately on our budget.
    So I think we all do need a sense of urgency about how we
can come to grips with this and accelerate what we're going to
do.
    I want to welcome the witnesses here, Dr. Collins, Dr.
Landis, Dr. Hodes. I was just at NIH on Monday. I'm so proud of
the fact that it's in Maryland. I call it the National
Institutes of Hope. The National Institutes of Hope. And I
think that's what brings all the men and women and family
members here.

      HOW BEST TO ACCELERATE BREAKTHROUGHS IN ALZHEIMER'S DISEASE

    My question, because we've been able to do something in
this year's appropriations--and I might add, every single
Senator up here is also a member of the appropriations
committee--and we can feel proud of the fact that we put close
to $30 billion into NIH, a billion more than last year. We've
increased the National Institutes of Aging by $100 million.
We've included money for the BRAIN initiative. So we think
we're making that progress. And that comes to me, Dr. Collins,
and other esteemed witnesses.
    We would like to be able to accelerate these breakthroughs
which you just testified seem so promising. But I feel that we
also need a sense of urgency, because we are facing an epidemic
in this country and the impact, again, on family budgets and on
our Medicaid budget, of course, ultimately the impact of people
being in long-term care. I remember what Senator Harkin and
Senator Specter did when they doubled it.
    Is it that we need more money? Do we need more people going
into science? What do we need to put this on the fast track so
that these promising breakthroughs, following all the rubrics
of the scientific method? How can we? Because the clock is
ticking, and the numbers are growing. The poignancy is there.
Could you share how we can help move this along?
    Dr. Collins. I appreciate the question, Senator, and it was
great hosting you at NIH on Monday.
    I think we are not at the moment limited by ideas. We're
not limited by scientific opportunities. We're not limited by
talent. We are, unfortunately, limited by resources to be able
to move this enterprise forward at the pace that it could take.
And it would be, of course, great to see that achieved. And it
would actually, even setting aside the pressing need for the
benefits to health, it would also be a nice investment in our
economy since, as many of you know, the way in which we put
dollars into medical research pays back more than twofold in
just a single year.
    At the moment, people who have great ideas about
Alzheimer's disease who come to NIH with those--and again, we
have some ideas about areas that we think are exciting, but we
also count on our community to come up with ideas that we, the
three of us, couldn't necessarily have thought about, and to
send us those. And we put them through the most rigorous peer
review process. But their chance of getting funded right now is
about one in six.

              IMPACT ON LOW SUCCESS RATE ON INVESTIGATORS

    Senator Mikulski. One in six?
    Dr. Collins. So, five out of six are going away with
nothing. The community is incredibly struggling and demoralized
about that. You and I looked at this survey from the Chronicle
of Higher Education on Monday--that just came out on Monday,
indicating what's happening to investigators in laboratories
all over the country.
    [The information follows:]

    The restricted link for the Chronicle of Higher Education article
can be found at: http://chronicle.com/article/Strapped-Scientists-
Abandon/144921/.

    Dr. Collins. Remember, NIH is not just in Bethesda; most of
our money goes out to all 50 States where this research is
going on. And more than half of those investigators are saying
they've basically had to let somebody go or they can't take on
a student that they wanted to, or they're not going to start a
project that they're excited about but they don't think they
have the resources to do it. We are constraining the energy,
the innovation, the creativity of the most amazing engine for
discovery the world has seen, which is America's science.
    Senator Mikulski. Well, Dr. Collins, what you're saying is
that young people are discouraged from coming forth because
they don't think that there's going to be the money there to
fund their project. I see Dr. Hodes and Landis shaking their
head.
    Dr. Collins. Yes.
    Senator Mikulski. Is that right? So we have promising ideas
and people in our own country--in our own country--with these
ideas ready to roll.

      WHERE WOULD WE BE IF WE HAD STAYED ON 3-PERCENT GROWTH RATE

    Well, let me ask you this. The whole idea of doubling: I
don't know if it was in our fiscal cards, but I understand we
shared an idea here that if we had stayed on the 3-percent
growth initiated by Arlen Specter, where would we be now? At
about $40 billion?
    Dr. Collins. If you look at that curve of what the
trajectory was prior to the 1998 doubling, it was about a 3-
percent growth rate, and that's accounting for inflation, so
real growth in terms of purchasing power. If we had stayed on
that curve, we would now be just at about $40 billion.
    Senator Mikulski. So it's $10 billion less than where we
are for both not only at the National Institute of Aging, but
as you pointed out, this could be in a variety of other
institutes, from Dr. Landis's on neurological behavior,
everything.

                        INFLATION PLUS 5 PERCENT

    So here's my question. I understand you have an idea that
if we took inflation plus 5 percent for about 4 years, we could
get to where we are today.
    Dr. Collins. That would, if you do the math, carry NIH back
up to that $40 billion number, if it were possible to do that.
And again, that's a decision that is up to the Congress, the
administration, the American people. But I must say, from my
perspective, the best thing we could do for science would be to
get on that kind of a stable, predictable trajectory so we can
plan more than 3 months at a time, so we can actually tell
young people who are coming into the field, ``There's a career
for you.'' ``America is going to invest in this.'' ``You can
count on, if you have a great idea, you're going to be able to
be part of an adventure that is going to be exciting and world-
changing.''
    Right now, people aren't quite sure. This up and down and
uncertainty has really done quite a lot of damage to the
momentum.
    Senator Mikulski. Well, thank you, Dr. Collins, and also
the wonderful people there. My time is up. But I look forward
to--really, this seems to be an achievable goal if we put our
minds to it.
    Dr. Collins. Thank you, Senator.
    Senator Harkin. Thank you, Senator Mikulski.
    And Senator Shelby.

             ALZHEIMER'S DISEASE NOT CURRENTLY PREVENTABLE

    Senator Shelby. Thank you.
    Dr. Collins, I just want to share some statistics I have
and see if you agree with them. I bet you would, but I don't
know. That Alzheimer's is the only cause of death among the top
10 causes in America without a way to prevent it, cure it, or
even slow its progressions. Is that true here in America? And
what about in some of the European countries like Germany and
England, France, Switzerland, more industrialized countries?
Are these statistics prevalent there, too?
    Dr. Collins. Yes, sir, they would be. I mean, the
Alzheimer's epidemic is not just the U.S., it's worldwide. And
it's a function of the aging of our population, which is, by
the way, a good problem that medical research has contributed
to. One hundred years ago, Alzheimer's was barely known because
people didn't live long enough to get it. Now we've created a
wonderful possibility of longer life, but with it has come this
new responsibility to do something about Alzheimer's.

             RISK OF ALZHEIMER'S DISEASE INCREASES WITH AGE

    Senator Shelby. So some of us that hope to be in our 90s
someday, and there's a good chance we might have symptoms of
Alzheimer's or even have it or have acute cases of it; is that
correct?
    Dr. Collins. Well, Dr. Hurd, who is in the second panel, in
the study he published in The New England Journal kind of went
through those. And as I recall, people in their 90s, the
incidence of Alzheimer's or some form of dementia is up there
in about 30 percent.

 ALZHEIMER'S DISEASE TRANSLATIONAL RESEARCH AT NATIONAL INSTITUTES OF
                                 HEALTH

    Senator Shelby. Tell us about how some of the translational
research that's going on at NIH hopefully will affect maybe a
slow-down or cure for this.
    Dr. Collins. Well, translation is the process of going from
basic science discoveries, translating those into clinical
benefit. And that is a major focus of all of the parts of NIH.
All 27 institutes have an investment in that. I think I'll ask
Dr. Hodes for Alzheimer's to give a quick snapshot of some of
the most of exciting areas of translation we're pursuing right
now.
    Dr. Hodes. Thank you. I can really organize thoughts along
the lines of Dr. Collins's response to the areas of hope and
progress over the past 5 or 10 years because they really do
range from basic discovery through their translation.
    The level of basic discovery, he noted, for example, the
number of new genetic risk factors and protective factors that
we're finding. With funding that was made available this year,
we're going to be able to expand new analyses that will look at
not just single genes or proteins, but the way they interact in
very complex ways, contrasting what goes on in a normal brain,
in a diseased brain.
    And these were already identifying critical points that
seem to be central to disease. That means we can test that
hypothesis by tracking and interventions such as a drug or
small molecule to that specific process. Find out in a single
cell or in an animal model if that has the right effect, and
then translate those into clinical studies.
    For translation, again to emphasize what Dr. Collins has
noted, we now have the capability of beginning interventions at
a stage at which we can track disease long before extensive
cell death and damage has occurred in the brain. We can also
track the effectiveness of treatment through biomarkers.
    The biomarkers will be the ones that we know now, and new
markers that will develop as we learn more about the progress
of disease. So everything is about translation. And in fact, in
the planning in process now for 2015 and years beyond, with the
benefit of this increased funding by appropriation, we will be
looking at precisely the right balance of initiatives across
this whole spectrum, from discovery, translation, to clinical
trials for the most promising of initiatives.
    And this is an ongoing effort. We'll meet periodically with
the best minds in the Nation and internationally to revise
those plans. But translation is what is primarily in line for
this whole effort. And I think progress at each of these
levels, from basic science through clinical trials, is going to
support acceleration with full utilization of the resources
that are made available to us.

       STEM CELLS AND ALZHEIMER'S DISEASE TRANSLATIONAL RESEARCH

    Dr. Collins. Let me add one other translational thing
that's pretty exciting. And that is based on stem cells. The
ability now to be able to take a skin biopsy or a blood sample
from somebody with Alzheimer's disease and, by adding just four
genes, convince those cells to go back in time and become what
you'd called pluripotent. Then having achieved that, add a
certain number of growth factors and convince those cells to
become neurons.
    So you can take somebody with Alzheimer's disease with a
skin biopsy and a blood cell and study their neurons, sort of
the disease in a dish. And already that's been done. And it's
clear that you can tell the difference in those neurons if they
came from somebody with Alzheimer's versus somebody who
doesn't.
    That is an incredibly exciting opportunity, to be able to
understand the disease in a system where you can really work
closely with it, and even use it as a drug screen because you
could then take 1,000 or 100,000 drugs and say, ``Which of
these make the Alzheimer's cells look like the normal neurons?
How could you do that?''

                           LONGEVITY RESEARCH

    Senator Shelby. Dr. Collins, one last question. My time is
up. In your research, do you do research into animals that live
longer than others and see if there are some corresponding
problems with their aging process? And if so, could you speak
to that?
    Dr. Collins. Well, this is the central role of the National
Institute on Aging--is to look at the whole question of
longevity.
    Senator Shelby. I need to visit with Dr. Hodes.
    Go ahead, Dr. Hodes.
    Dr. Hodes. Yes. Looking at varied species with different
lifespans and expectancies is a very important part of the
research that's ongoing and is still a mystery, the solution to
which is unraveling.
    So, for example, we know that examples that have been given
for different kinds of clams that live in the same environment,
some species of clams will have a life expectancy of no more
than a year or two, others 500 years, the longest life
expectancy of any animals. Trying to understand the reason for
that so-called comparative genetics is an important area.
    We know that if one takes certain species, flies and worms
happen to be those which are very easily manipulated, with
single or multiple genetic changes in those animals, we can
extend their lifespan several-fold, maybe three-, four-, six-,
or tenfold.
    Now, that obviously reveals something about the basic
pathways that determine health and life expectancy. And now the
real promise and the excitement currently is translating that
to the equivalent pathways in humans to understand whether
manipulating those pathways will improve health and lifespan.
So a very informative area of research.
    Senator Shelby. Thank you both.
    Thank you, Mr. Chairman.
    Senator Harkin. Thank you, Senator Shelby.
    Senator Cochran.

     SHOULD THERE BE CRASH COURSE ENDEAVOR FOR ALZHEIMER'S DISEASE

    Senator Cochran. Mr. Chairman, thank you. Thank you all for
joining us today to discuss this situation.
    I'm reminded that at the University of Mississippi, Dr.
Arthur Guyton embarked upon a study of the heart. And flowing
from the research that he managed and was in charge of at the
university, a textbook was written and great strides were made
in understanding and prescribing changes in lifestyles and
medications that could have this effect or that effect on the
human heart.
    Is it time now for us to encourage and identify someone or
someplace where a crash course in research and emphasis on this
horrendous disease called Alzheimer's can be undertaken, maybe
with the hope of marshalling the best minds and the greatest
techniques of research that we have, and take one step into the
future, where your name might be on a textbook?
    What's your reaction to that? Do we have the capacity to do
that? What amount of funding should we urge the Senate to
consider appropriating for such a crash course endeavor?
    Dr. Collins. That's an interesting question. To think back
about Dr. Guyton and the incredible impact that he had and
reverberates down through the decades on what we understand
about the heart.
    Over the course of those decades, we have moved more and
more into a realization that for the current challenges, it's
bringing disciplines together that seems to be the most
promising way to make progress. And certainly in Alzheimer's
disease, the idea that you can bring together people who know
something about neuroscience, people who know something about
clinical medicine, people who know about imaging technologies,
people who study genomics, people who are engineers, robotics
experts, big data is a big part of this now--that's where a lot
of the excitement is.
    And so, increasingly, what we need to do, sort of the
modern version of Dr. Guyton, is to come up with teams that are
made of many brains sort of working together. And that is very
much the way science is now proceeding.
    The BRAIN initiative, which Dr. Landis co-leads for us, is
a great example of how to achieve that. I don't know. Maybe you
could say a word about how that is coming together in a way
that reflects this change in the dynamics.
    Dr. Landis. So it's very clear that we've made excellent
advances in understanding brain structure. We know we have
crude wiring diagrams for the brain. But we don't know how
information is processed along those wires, how the vision of a
rose actually gets translated through many, many different way
stations in the brain to recognition that this is a rose and
the expectation that it will smell sweet.
    And what we need to do to really understand how the
circuits work--that's the organization of the brain, brain
cells--is to bring together neuroscientists, computational
people, physicists, chemists, engineers, to work to develop
tools that we then can apply to answer those questions about
how brain circuits really function. And that obviously starts
with normal brain circuits.
    But what we learn from understanding normal brain function
will have significant implications for diseases like
Alzheimer's, other kinds of dementia, Parkinson's disease,
epilepsy. And so we hope to build those kinds of teams that Dr.
Collins spoke about to really unravel the language of the
brain.
    Dr. Hodes. Yes. First I have to agree with the appreciation
for the remarkable Guyton family. One of the Drs. Guyton was a
classmate of mine in medical school, and they are clearly
remarkable folks.
    But in line with your suggestion of a new kind of center
that will allow a translation from basic observations through
at least preclinical stages, in fact, the very existence of the
additional appropriation this year has led us to begin a set-
aside of funds for planning grants for a translational center.
In fact, the concept just approved this morning by our advisory
council, the concept developed and now implemented in the
context of funds available.
    So it's intended to do just the sort of thing you were
mentioning, I think, will bring together, as Dr. Collins
mentioned, individuals from multiple disciplines to look at new
ways to integrate and, hopefully, accelerate progress in this
area.
    Senator Cochran. Thank you very much.
    Thank you, Mr. Chairman, for calling this hearing.
    Senator Harkin. Thank you very much, Senator Cochran.
    Senator Kirk.

   NATIONAL INSTITUTES OF HEALTH ACCELERATING MEDICINES PARTNERSHIP
                               INITIATIVE

    Senator Kirk. Mr. Chairman, I just wanted to highlight and
praise Dr. Collins for the AMP effort that brings together 10
pharmaceutical companies. I'll mention them: ABBVie, I will
note, headquartered in Illinois, Biogen, Bristol-Myers Squibb
GlaxoSmithKline and Johnson & Johnson, and Lilly and Merck and
Pfizer and Sanofi, Takeda, all part of AMP.
    I would say that, institutionally, these are all
shareholder-sponsored entities who all are going to be very
interested in bringing something to market eventually, which
actually means actual patients will be helped, and not a 25-
year research pact where, with all these institutions coming
into play, they're only interested in the clinical application
of what they find.
    And for a lot of the people who are in the sessions here, I
am sure that that's what they're most focused on.
    Dr. Collins. Senator, I appreciate your raising AMP,
because I'm personally very excited about this and have put
close to 3 years into trying to build the momentum and was
thrilled that it was possible to announce this just a couple of
weeks ago.
    It is unprecedented to have NIH and academic researchers
getting together around the same table with equal financial
contributions with these 10 pharmaceutical companies, to say,
``This is a hard problem. Let's work on it together,'' and with
an agreement that all the data is going to be publically
accessible.
    So we're calling this no longer a competitive part of the
process. This is pre-competitive. But the opportunities now,
because of the proliferation of discoveries about basic science
that's involved in Alzheimer's and in diabetes and in
rheumatoid arthritis and in Lupus, to try to move those to the
clinic has never been greater. But it's a little overwhelming
to see how exactly to do that. And those 10 companies kind of
came to the conclusion no single one of them could do this in
the kind of timeframe that is necessary.
    So let's just get together and do it as a team and
recognize that, once we've done this pre-competitive part, the
companies are going to jump in, and they're going to race each
other to try to get to the end point of having an FDA-approved
drug. And we want them to. That part of competition is how we
get to ultimately the treatments that people are waiting for.
    But it's a very exciting model. It's been never tried like
this. Watch us closely now. We put ourselves in a position of
having to deliver on some very ambitious milestones. But I
think we'll get there. And it's going to be great also to mix
these cultures together, the culture of the academic scientists
and the private sector scientists with different kinds of
ideas, but agreeing as deep as their DNA that what they're
really at here is to try to solve problems and help patients.
Thank you.
    Senator Kirk. And I just want to make it clear. This
information is shared across all the companies and the public
and everybody?
    Dr. Collins. Absolutely. Absolutely. Yes. Some of the
companies initially were like, you know, ``Why should we join,
because if we sort of sit on the outside and watch, we're still
going to see the data.'' Right?
    Senator Kirk. That's right.
    Dr. Collins. Yeah, they'll sit on the outside. But if
you're on the outside, you're not actually able to steer the
project. You're not able to say, ``Oh, why don't we try that?''
So being part of the team here is going to be significant and
useful and, I think, very exciting for the participants.

                  ACCELERATING AND ALZHEIMER'S DISEASE

    I should have said Alzheimer's is one of the projects that
was chosen. We had to figure out which of these various disease
opportunities were the companies excited enough about to put
money on the table. And Alzheimer's was one of those. In
Alzheimer's, the goal is going to be very much to see what we
could do about these biomarkers that relate to identifying
whether a therapy is working or not, and also to study these
brain networks that Dr. Hodes was talking about to identify new
targets for drug treatment that we don't know about already.
It's going to be very interesting.
    Senator Harkin. Again, thank you and congratulations for
pulling this group together. Quite a feat.
    Senator Alexander.

                  ``MOONSHOT'' FOR ALZHEIMER'S DISEASE

    Senator Alexander. Thanks, Mr. Chairman. Thanks, Dr.
Collins, and to all of you. Of course, we greatly admire what
you've done. I think we've all asked you about the same
question, so let me ask you again and make sure I understand
it.
    A moon shot had a very specific goal, and all the
incredible human activity, was organized around that specific
goal. I suppose mapping the human genome was a very specific
goal. And all this activity was organized around that goal. So
you knew when you got to the moon, and you knew when you'd
finished mapping the sequence that you worked on.
    What is the AMP? The equivalent of those big crash courses
that Senator Cochran called them, or goals? Or is there a
better goal? I think what I'm asking, I think every one of us
may have asked, is: What would be the equivalent here in terms
of brain research or in terms of Alzheimer's? What should the
goal be? And then how much money should a great country put
behind that to reach the goal?
    In my work in public life, it's always seemed to me that
the money was not the problem; the goal, defining the goal
usually was the problem. If the goal was compelling enough,
usually the resources would follow the goal.
    So tell me again what the equivalent of the moon shot or
the Human Genome Project is here so I understand it clearly.
And then remind me again, if you know, what it would cost to do
it.
    Dr. Collins. That's the hardest part because we don't know
what the trajectory is going to be. But let me try and see if I
can address your very thoughtful question.
    You're right. The moon shot, the Human Genome Project,
those were unique situations where you could define a very
precise endpoint and everybody would know whether you got there
or not. You've got a man on the moon. Okay, you did it. You
read out 3 billion letters of the DNA instruction book. Okay,
you did it.
    For Alzheimer's disease, what would be an appropriate goal?
There's going to be lots of goals in there. Getting diagnosis
so that it is accurate and can be done early, before symptoms.
We're coming along pretty well on that one. I wouldn't say
we're there. But of course, the big goal is prevention,
treatment, so that nobody gets this disease anymore. That is
far enough out in the future that I think it's hard for us,
with the uncertainties about how we will get there, to be able
to put a timetable on that. But people are trying.

                 NATIONAL PLAN FOR ALZHEIMER'S DISEASE

    I'm going to ask Dr. Hodes to say something about the
national plan.
    Senator Alexander. Before you do, is the goal to prevent
anyone from getting Alzheimer's just like we say today polio's
gone from the United States?
    Dr. Collins. That would be my goal. That would be my goal.
That's very bold, very ambitious. But that's got to be the
place to try for.
    Now, I'm going to ask Hodes to say something about
Alzheimer's plan, the national plan. But we also have this
BRAIN project. And it's holding itself accountable. Kind of
like a genome project, it's going to stretch out over a decade
or so. But it needs to have clear indications of whether it's
succeeding or not, milestones.
    I think maybe that's the difference, that even with the
moon shot, you had to have milestones about whether you're
going to get there. Can you put a man in orbit? Can you
actually go around the moon and come back? And then,
ultimately, can you put somebody on the moon?
    Maybe Dr. Landis could say just a word about BRAIN in terms
of how we are trying to set those specific milestones so that
we can say we're getting there. And then you can perhaps say
something about the Alzheimer's plan.
    Dr. Landis. So, as I said, we have maps of the connections
in the human brain. But what we don't have is a way to record
from the 86 billion neurons and the 1,000 connections that each
of them has in order to understand how the brain actually
functions.
    So, what we need to do is to be able to record, not just
from 1 neuron or 10 neurons or 100 neurons, but thousands or
tens of thousands of neurons at the same time as a person, or
an animal to start with, is performing a behavior, and then to
reconstruct how those circuits, those brain cells, actually
directed that behavior.
    And if we could do that, it would give us a much better
understanding of this amazing computational machine that
accomplishes actions and thoughts that no computer could ever
replicate.
    Dr. Collins. And there are milestones.
    Dr. Landis. And there are milestones. In fact, those
milestones are being developed and will be presented to the
Advisory Committee to the Director. We have requests for
applications out on the street now that have discrete pieces of
that problem that we will fund projects to answer, different
steps in that process.
    Dr. Collins. Richard, maybe you can say just a quick word
about the national plan because it's all about milestones.
    Dr. Hodes. Yes. The national plan establishes and has
established long-term goals including the very ambitious goal
by 2025 of generating an effective means of treatment or
prevention. What we then did is to ask: What would be necessary
in order to reach that success by that date, and from there,
set a series of specific research objectives and milestones so
that in 2013 and 2014 there are investments in certain areas of
research, which as projected, if successful, will lead in 2025
to ultimate success?
    We don't know which of the approaches we take are going to
succeed, which are going to fail. But the milestones are
designed to set out an approach that has the potential for that
success. Ambitious as it is, we have no choice, given the
urgency, but to move towards just that accelerated a course.
    Senator Alexander. Thank you, Mr. Chairman.
    Senator Harkin. Thank you, Senator Alexander.
    I thank you again, Dr. Collins, Dr. Landis, Dr. Hodes, for
being here today. Again, congratulations on bringing together
the drug companies on this AMP (Accelerating Medicines
Partnership) project. I think it's just a milestone. And again,
hopefully, we'll be able to continue our funding in the next
fiscal year like we did in the last fiscal year.
    And again, I would be remiss if I didn't thank the chairman
of our full committee for giving us the allocation with which
to do that.
    Thank you all very much.
    And we'll now turn to our second panel.

             ``MANHATTAN PROJECT'' FOR ALZHEIMER'S DISEASE

    Senator Mikulski. But, Mr. Chairman, if I could, really I'd
also raise kind of Manhattan-like project, the genome, landing
on the moon, the Manhattan Project. Wasn't one of the biggest
concerns, the fact that would be discouragement to or an
impediment, two things, the shutdown of our Government and the
other is sequester? So that there is the lack of certainty, as
you have to not only sequence the human genome, but you've got
to sequence what you're going to do when, in terms of research,
recruitment, retention and so on.
    Don't you need certainty as well as resources?
    Dr. Collins. Absolutely. People say that the worst thing
you can do to the business community is uncertainty. Well,
that's true for science even more so. Our cycle time for
projects runs about 4 years in order to come up with an idea,
put it into practice, work really hard, and see if it works.
    When your cycle time for support sometimes is 3 months, and
we've been there for some of these continuing resolutions. And
certainly, when you lose $1.5 billion halfway through the
fiscal, as we did with sequester, it's very damaging to the
ability for people to pursue momentum and to be innovative and
to take risks. We want them out there taking risks, not
worrying about whether somehow they're just going to miss the
pay line because it's so tight.
    If we can find our path forward, Madam Chairwoman, to that
kind of a stable support for medical research in the United
States, it would make a huge difference.
    Senator Harkin. I can't help, then, but add here that years
ago Mark Hatfield, Senator Hatfield came up with an idea.
    Senator Mikulski. Yes.
    Senator Harkin. And I joined with him on it, and so did
others. He pointed out that every time you buy a drug at a
drugstore, every time you buy an off-the-shelf drug or even a
prescription drug, some of that money goes for research. When
you buy a health insurance policy, none of it goes for
research.
    Think of the amount of money we spend every year on our
health insurance policies to treat and to take care of
illnesses. But none of it goes for research. So, Senator
Hatfield came up with the idea, it was a long time ago, about
having, I think it was 2 or 3 cents if I'm not mistaken, out of
every healthcare dollar appropriated would go to NIH for
research.
    And of course, the argument was made, well, that would just
supplant the money that we were doing. So he said no. What you
do is, as long as this committee funded NIH, or the Congress
funded NIH at a minimum of inflation, then that money would
flow on top of it and be a supplement to it. I've been
preaching this for 25 years, that some of this health insurance
money that we spend ought to go for research. And I'm sorry
that the health insurance industry has always opposed it. But
it seemed to me that this is one way of getting some amount of
money that you know every year is going to be there.
    With that, thank you very much, Dr. Collins. We'll turn to
our second panel.
    Dr. Collins. Thank you.

                       NONDEPARTMENTAL WITNESSES

    Senator Harkin. Now we'll call our second panel, Dr.
Michael Hurd, Congressman Dennis Moore, and Mr. Seth Rogen. And
while they're coming to the table, I will go ahead and
introduce them.
    First, Dr. Michael Hurd, a senior principal researcher at
the RAND Corporation, where he directs the RAND Center for the
Study of Aging. He is also a professor at the Pardee RAND
Graduate School in Santa Monica, California. Dr. Hurd's
research focuses on the economics of retirement, Social
Security and social welfare systems, and other topics related
to aging and the elderly.
    We have Congressman Dennis Moore, who represented the Third
District of Kansas in the U.S. House of Representatives for 12
years. First elected in 1998, Congressman Moore served on the
Budget and Financial Services Committees. In 2010, he announced
he would not seek re-election. Prior to his time in office,
Congressman Moore served in the U.S. Army and the U.S. Army
Reserve, was an assistant attorney general for the State of
Kansas, Johnson County District Attorney, as well as a private
practice lawyer.
    In February 2012, he and his wife Stephene announced that
he, Congressman Moore, had been diagnosed with Alzheimer's
disease.
    Mr. Seth Rogen, a stand-up comedian, actor, producer,
director, screenwriter, and voice actor. Originally from
Vancouver, British Columbia, Mr. Rogen began his career
performing stand-up comedy, moved to Los Angeles to pursue
acting in the late 1990s. Since that time, Mr. Rogen has acted
in and co-written major movies, as well as done voice-over work
for animated films.
    Mr. Rogen raises awareness of Alzheimer's disease as a
celebrity champion for the National Alzheimer's Association.
Alzheimer's has greatly affected his wife's family, and he will
talk about that.
    We welcome you all here. I read your testimonies last
night. They are great. All your testimonies will be made a part
of the record in their entirety. And I would ask if you would
give a short 5-minute summation of that so we can engage you in
questions and answers and conversation.
    First, we'll recognize our former colleague from the House
side, Congressman Dennis Moore. Good to see an old friend back
again from the Midwest.
    Dennis, thanks for being here, and please proceed.
STATEMENT OF DENNIS MOORE, FORMER U.S. CONGRESSMAN FROM
            THE THIRD DISTRICT OF KANSAS
    Mr. Moore. Thank you. Good afternoon, Chairman Harkin,
Ranking Member Moran, and members of the subcommittee. As an
individual living with Alzheimer's disease, I thank you for the
opportunity to testify here before this subcommittee.
    Alzheimer's is a devastating progressively and ultimately
fatal disease. It currently impacts more than 5 million
Americans. These men and women are husbands and wives, mothers
and fathers, sisters and brothers, Republicans and Democrats. I
should know; I'm a former member of the United States House of
Representatives, and I'm one of them.
    I was diagnosed with Alzheimer's disease almost 3 years ago
on June 1, 2011. I had become concerned when I noticed I was
having some difficulty remembering random events and difficulty
managing our household finances.
    Since then, I've learned coping skills, but still recognise
the issue I have with my short-term memory loss. I'm now an
Alzheimer's advocate for the Alzheimer's Association because I
know personally how this disease affects an individual and
family.
    There is a great need for educating the general public and
funding research for a cure. Not only does Alzheimer's steal
our memories, independence, and eventually our ability to
function, but it demands increasing amounts of care. Beyond the
exhaustion and stress, there's the financial burden. The direct
cost of Alzheimer's and related dementia is greater than any
other condition in the United States, including heart disease
and cancer, according to a recent study in The New England
Journal of Medicine.
    [The information follows:]

    The link for The New England Journal of Medicine article can be
found at: http://www.nejm.org/doi/full/10.1056/NEJMsa1204629.

    Mr. Moore. Over the next 40 years, caring for people with
Alzheimer's and related dementias will cost $20 trillion--
trillion. However, even with this information, for every
$27,000 Medicare and Medicaid spend on caring for individuals
with Alzheimer's, the National Institutes of Health spends only
$100 on Alzheimer's research--$100 on Alzheimer's research.
    Fortunately, Alzheimer's is a bipartisan issue. In 2010,
Congress unanimously passed the National Alzheimer's Project
Act.
    [The information follows:]

    Public Law 111-375--January 4, 2011--Legislative History: S. 3036:
      December 8, considered and passed the Senate.
      December 15, considered and passed the House.

    Mr. Moore. The act mandated the creation of the first-ever
National Alzheimer's Plan, which was released in May 2012 with
the goal of preventing and effectively treating Alzheimer's by
2025. Recently updated, the plan now includes important
milestones and a timeline to facilitate achieving that goal.
    However, goals of this magnitude, goals aimed at changing
the trajectory of a national health crisis require significant
investments if we hope to realize success. Recognizing this, we
commend Congress, through their leadership of you, Chairman
Harkin and Ranking Member Moran, for providing an historic
increase for Alzheimer's in the Consolidated Appropriations Act
of 2014. This is an important down payment and step in
implementing the National Alzheimer's Plan so we can reach the
goal of effectively treating and preventing Alzheimer's by
2025.
    This critical funding will allow scientists to pursue
innovative research that will lead to new treatments,
interventions, and diagnostics. Continued funding of these
programs will encourage a greater investment in the academic
and private sector and ultimately lead to a game-changing
diagnostic or treatment.
    For all of these reasons, it's vital that we continue to
make investments in Alzheimer's disease research, education,
outreach, and support activities to implement the National
Alzheimer's Plan as we look to fiscal year 2015.
    In order to take full advantage of the potential of the
National Alzheimer's Plan, Congress must see to it that the
necessary resources are committed to accelerate and prioritize
the Government's efforts on Alzheimer's. The infusion of
funding for fiscal year 2014 took the next step in recognizing
the correlation between investments in Alzheimer's research
today and a much healthier and sounder financial future for our
Nation.
    It is now incumbent upon our Nation's leaders to ensure the
promise of the National Alzheimer's Plan. My fellow Alzheimer's
advocates and I thank you again for your support in fiscal year
2014 and urge you to stay committed to Alzheimer's as you start
discussions for fiscal year 2015.

                           PREPARED STATEMENT

    An epidemic is upon us, and too many families are in
situations like mine, facing a fatal disease that currently has
no way to prevent, cure, or even slow its progression. As a
nation, we cannot afford to wait until Alzheimer's bankrupts
us. We must make the smart investment now to realize a better,
healthier future for our families and our country. Thank you
very much.
    [The statement follows:]
                Prepared Statement of Hon. Dennis Moore
    Good afternoon Chairman Harkin, Ranking Member Moran and members of
the subcommittee. As an individual living with Alzheimer's disease,
thank you for the opportunity to testify before the subcommittee.
    Alzheimer's is a devastating, progressive and ultimately fatal
disease. It currently impacts more than 5 million Americans living with
the disease and their 15.4 million caregivers. These men and women are
husbands and wives, mothers and fathers, sisters and brothers, business
leaders, medical professionals, Republicans and Democrats. I should
know. I, a former member of the U.S. House of Representatives, am one
of them.
    I was diagnosed with Alzheimer's disease just 2 years ago on June
1, 2011. I had become concerned when I noticed I was having some
difficulty remembering random events and difficulty managing our
household finances. Since then, I have learned coping skills but still
recognize the issue I have with my short-term memory loss. I am now an
Alzheimer's advocate for the Alzheimer's Association and serve on the
Advisory Council on Alzheimer's Research, Care, and Services because I
know personally how this disease affects an individual and family.
There is a great need for educating the general public and funding
research for a cure.
       alzheimer's impact on the american people and the economy
    In addition to Alzheimer's stealing our memories, independence and
eventually our ability to function, it demands increasing amounts of
care. Beyond the exhaustion and stress, there is the financial burden.
Alzheimer's is creating an enormous strain on the healthcare system,
families and the Federal budget. Alzheimer's is a progressive brain
disorder that damages and eventually destroys brain cells, leading to a
loss of memory, thinking and other brain functions. Ultimately,
Alzheimer's is fatal. Currently, Alzheimer's is the sixth leading cause
of death in the United States and the only one of the top 10 without a
means to prevent, cure or slow its progression. Over 5 million
Americans are living with Alzheimer's, with 200,000 under the age of
65.
    A Federal commitment can lower costs and improve health outcomes
for people living with Alzheimer's today and in the future. By making
Alzheimer's a national priority, we can create the same successes that
we have been able to achieve in other diseases that have been
prioritized by the Federal Government. Leadership from the Federal
government has helped to lower the number of deaths from other major
diseases like heart disease, HIV/AIDS, many cancers, heart disease and
stroke. While those deaths have declined, deaths from Alzheimer's have
increased 68 percent between 2000 and 2010.
    Alzheimer's is the most expensive disease in America. In fact, an
NIH-funded study in the New England Journal of Medicine confirmed that
Alzheimer's is the most costly disease in America, with costs set to
skyrocket at unprecedented rates. In 2013, America is estimated to have
spent $203 billion in direct costs for those with Alzheimer's,
including $142 billion in costs to Medicare and Medicaid. Average per
person Medicare costs for those with Alzheimer's and other dementias
are three times higher than those without these conditions. Average per
senior Medicaid spending is 19 times higher. A primary reason for these
high costs is that Alzheimer's makes treating other diseases more
expensive, as most individuals with Alzheimer's have one or more co-
morbidities that complicate the management of the condition(s) and
increases costs. For example, a senior with diabetes and Alzheimer's
costs Medicare 81 percent more than a senior who only has diabetes.
    If nothing is done, as many as 16 million Americans will have
Alzheimer's disease by 2050 and costs will exceed $1.2 trillion (not
adjusted for inflation), creating an enormous strain on the healthcare
system, families and the Federal budget. The expense involved in caring
for those with Alzheimer's is not just a long-term problem. As the
current generation of baby boomers age, near-term costs for caring for
those with Alzheimer's will balloon, as Medicare and Medicaid will
cover more than two-thirds of the costs for their care.
    With Alzheimer's, it is not just those with the disease who
suffer--it is also their caregivers and families. In 2012, 15.4 million
family members and friends provided unpaid care valued at over $216
billion. Caring for a person with Alzheimer's takes longer, lasts
longer, is more personal and intrusive, and takes a heavy toll on the
health of the caregivers themselves. More than 60 percent of
Alzheimer's and dementia caregivers rate the emotional stress of
caregiving as high or very high, with one-third reporting symptoms of
depression. Caregiving also has a negative impact on health,
employment, income and finances for countless American families. Due to
the physical and emotional toll of caregiving on their own health,
Alzheimer's and dementia caregivers had $9.1 billion in additional
health costs in 2012.
                 changing the trajectory of alzheimer's
    Until recently, there was no Federal Government strategy to address
this looming crisis. In 2010, thanks to bipartisan support in Congress,
the National Alzheimer's Project Act (NAPA) (Public Law 111-375) passed
unanimously, requiring the creation of an annually updated strategic
National Alzheimer's Plan (Plan) to help those with the disease and
their families today and to change the trajectory of the disease for
the future. The Plan is required to include an evaluation of all
federally funded efforts in Alzheimer's research, care and services--
along with their outcomes. In addition, the Plan must outline priority
actions to reduce the financial impact of Alzheimer's on Federal
programs and on families; improve health outcomes for all Americans
living with Alzheimer's; and improve the prevention, diagnosis,
treatment, care, institutional-, home-, and community-based Alzheimer's
programs for individuals with Alzheimer's and their caregivers.
    As mandated by NAPA, the Secretary of Health and Human Services, in
collaboration with the Advisory Council on Alzheimer's Research, Care
and Services, developed the first-ever National Plan to Address
Alzheimer's Disease in May of 2012. The Advisory Council, of which I am
a member, is composed of both Federal members and expert non-Federal
members. It is an integral part of the planning process as it advises
the Secretary in developing and evaluating the annual Plan, makes
recommendations to the Secretary and Congress, and assists in
coordinating the work of Federal agencies involved in Alzheimer's
research, care, and services.
    NAPA, and the Plan it has yielded, finally provides a framework for
Congress to assess whether the Nation is meeting the challenges of this
disease for families, communities and the economy. The Plan sets
important goals. The first of these aims squarely at changing the
trajectory of Alzheimer's by setting the goal to, ``[p]revent and
effectively treat Alzheimer's disease by 2025.'' Further, to the great
credit of the National Institutes of Health and the National Institute
on Aging, our Nation's leading scientists have specified the annual
research milestones they have concluded they must achieve to remain on
track to accomplish this transformative goal. With these milestones in
hand, a direct product of NAPA, this subcommittee now has a tool to
constructively assess whether we remain on track toward 2025, whether
Congress is providing the necessary resources, and whether available
resources are yielding the anticipated progress from year to year.
Until this past year, such engagement between Congress and the National
Institutes of Health simply was not possible for lack of this
framework. We ought to recognize what a significant achievement this is
in the service of disciplined, priority-driven science, and I urge you
to take full advantage of it.
    Having this Plan with measurable milestones and outcomes is
important. But unless there are resources to implement the Plan and the
will to abide by it, we cannot hope to make sufficient progress. If we
are going to succeed in the fight against Alzheimer's, Congress must
provide the resources the scientists need. These funds are critically
needed for research and services for Alzheimer's patients and their
families.
    The potential in reach could scarcely be greater. A disease-
modifying or preventive therapy would not only save millions of lives
but would save billions of dollars in healthcare costs. Specifically, a
treatment that delayed the onset of Alzheimer's by 5 years (a treatment
similar to anti-cholesterol drugs), would reduce Medicare and Medicaid
spending nearly in half in 2050.
    Today, despite the Federal investment in Alzheimer's research, we
still must do much more to understand what causes the disease and to
capitalize on it. Americans are growing increasingly concerned that we
still lack effective treatments that will slow, stop, or cure the
disease, and that the pace of progress in developing breakthrough
discoveries is much too slow to significantly impact this growing
crisis. For every $27,000 Medicare and Medicaid spend caring for
individuals with Alzheimer's, the National Institutes of Health (NIH)
spends only $100 on Alzheimer's research. Scientists fundamentally
believe that we have the ideas, the technology and the will to develop
new Alzheimer's interventions. But that progress depends on
implementing NIH's prioritized Alzheimer's research agenda, and on
having the resources necessary to carry out the scientific strategy for
both discovery and translation for therapeutic development.
    Additional funding has been requested in the NIH budget over the
past several years because their scientists have determined that
additional research on Alzheimer's is a priority. These budget requests
reflect the changing needs of the Alzheimer's community, the scientific
opportunity, and the results of disciplined analysis and planning. It
is vital that Congress support the research projects the scientists at
NIH deem necessary.
    However, Congress does have a responsibility to direct resources to
solve the most serious problems. By every objective standard (whether
cost to Medicare/Medicaid, families caring for individuals with
Alzheimer's, or mortality rate), Alzheimer's is one of our most serious
health problems--and it will only get worse as the Baby Boomer
generation ages.
    While pursuing effective treatments for tomorrow, deliver better
care and support today Alzheimer's is the most expensive disease in the
country not just because of the lack of adequate treatments, but also
because our care systems do not effectively address dementia and its
consequences. For too many individuals with Alzheimer's and their
families, the system has failed them, and today we are unnecessarily
losing the battle against this devastating disease. Despite the fact
that an early and documented formal diagnosis allows individuals to
participate in their own care planning, manage other chronic
conditions, participate in clinical trials, and ultimately alleviate
the burden on themselves and their loved ones, as many as half of the
more than 5 million Americans with Alzheimer's have never received a
formal diagnosis.
    Unless we create an effective, dementia-capable system that finds
new solutions to providing high-quality care, provides community
support services and programs, and addresses Alzheimer's health
disparities, Alzheimer's will overwhelm the healthcare system in the
coming years. For example, people with Alzheimer's and other dementias
have more than three times as many hospital stays as other older
people. Furthermore, one out of seven individuals with Alzheimer's or
another dementia lives alone and up to half of them do not have an
identifiable caregiver. These individuals are more likely to need
emergency medical services because of self-neglect or injury, and are
found to be placed into nursing homes earlier, on average, than others
with dementia. Ultimately, supporting individuals with Alzheimer's
disease and their families and caregivers requires giving them the
tools they need to plan for the future and ensuring the best quality of
life for individuals and families affected by the disease.
    Recognizing this, President Obama's budget request for fiscal year
2014 included an increase of $80 million for Alzheimer's research at
NIA and an increase of $20 million for education, outreach and support
services. Congress, through the leadership of Chairman Harkin and
Ranking Member Moran, provided much needed resources in the
Consolidated Appropriations Act of 2014 that are allowing the pursuit
of the goal of effectively treating and preventing Alzheimer's by 2025
to continue into the next immediate steps without faltering.
    The funding provided in the Omnibus will allow scientists to pursue
innovative research that will lead to new treatments, interventions and
diagnostics. Continued funding of these programs will encourage a
greater investment in the academic and private sector and ultimately
lead to a game-changing diagnostic or treatment. For all these reasons,
it is vital that we continue to make investments in Alzheimer's disease
research, education, outreach and support activities to implement the
National Alzheimer's Plan as we look to fiscal year 2015.
                               conclusion
    Thank you again for the opportunity to testify today. I appreciate
the steadfast support of the subcommittee and its priority setting
activities. I look forward to continuing to work with Congress in order
to address the Alzheimer's crisis. Alzheimer's is the costliest disease
in the country and these costs are set to increase like for none other.
I ask Congress to address Alzheimer's with the same bipartisan
collaboration demonstrated in the passage of the National Alzheimer's
Project Act (Public Law 111-375) and this subcommittee's deliberations
on Alzheimer's, and with a commitment equal to the scale of the crisis.
An epidemic is well upon us, and too many families are in situations
like mine--facing a fatal disease that currently has no way to prevent,
cure or even slow its progression. As a nation, we cannot afford to
wait until Alzheimer's bankrupts the Nation, just as it already has so
many hardworking families in Iowa, Kansas, and all across this country.
We must make the smart investment now to realize a better, healthier
future for our families and our Nation. Thank you.

    Senator Harkin. I appreciate your being here and your
advocacy.
    Next, we'll turn to Dr. Hurd, the author of this famous
study that came out last year, I think, that really shook us
all up.
STATEMENT OF DR. MICHAEL HURD, DIRECTOR, RAND CENTER
            FOR THE STUDY OF AGING
    Dr. Hurd. Thank you for the kind words about that study. It
was challenging, as I'll outline now. Chairman Harkin and
Ranking Member Moran, thank you for the opportunity to testify
about the monetary costs of dementia in the United States.
    My testimony will be based upon research that co-authors
and I did at the RAND Corporation and the University of
Michigan, and it was published last year in The New England
Journal of Medicine. Emotional costs of dementia are
immeasurable. Our more modest goal was to measure the monetary
costs of dementia, but even so, there were a number of
challenges.
    [The information follows:]

    The link for the RAND study can be found at: http://www.rand.org/
pubs/
external_publications/EP50247.html.

    Dr. Hurd. First, most people with dementia have co-existing
health problems, such as a history of stroke or a heart
condition, which by themselves would lead to higher costs. We
wanted to find the cost attributable to dementia itself, not
the healthcare costs of people with dementia.
    A second difficulty concerns informal care, that is, unpaid
care most often performed by a family member. We had to develop
a method of placing a monetary value on that care, knowing it
could have a large effect on our estimates.
    These are other challenges made it difficult to find valid
and reliable data that were adequate for the needs of this
research.
    Fortunately, the National Institute on Aging, NIA, under
the leadership of Dr. Hodes and Dr. Richard Suzman, had the
foresight many years ago to invest in a data infrastructure,
the Health and Retirement Study, without which this research
could not have been accomplished. The HRS has become the
preeminent data source for general population representative
studies of aging. It provides a wide range of data, including
cognition, healthcare use, costs, and informal caregiving.
    However, the HRS lacked a measure of the dementia status of
its respondents. In 1998, a multidisciplinary team, including
myself, proposed and then fielded a small sub-study to diagnose
a sample of HRS respondents for dementia status. In our study
we used these diagnoses to estimate the dementia status of a
much larger HRS sample, around 6,000 persons.
    According to our results, in 2010, the prevalence of
dementia in the population aged 71 or older was 14.7 percent.
The annual healthcare spending attributable to dementia was
about $29,000 per person. The great majority of these excess
costs were for nursing home stays and paid in-home care. Adding
in the costs of unpaid or informal care increased total annual
cost per person to between $42,000 and $56,000, where the range
depends on the method of valuing informal care.
    We were not able to allocate costs between Alzheimer's and
other dementias, but we know that the great majority would be
due to Alzheimer's.
    We used census estimates of the population to estimate the
annual cost of dementia in the United States. We found that
actual spending attributable to dementia was $109 billion in
2010. This cost places dementia as the most costly disease in
the United States in terms of actual spending. Adding in costs
for informal care increased this estimate to a range of $160
billion to $250 billion per year.
    Because the prevalence of dementia sharply increases with
age, the aging of the population in itself, particularly when
the baby boom generation reaches an advanced age, will increase
future costs. The cost for care purchased in the marketplace
will increase in real terms from the 2010 value of $109 billion
to $260 billion in 2040. That's in real terms. Adding in the
costs of informal care increases the cost estimate to the range
of $380 billion to $510 billion per year in 2040.
    We are extending this research in two directions. Dementia
is very costly on average, but these costs are unequally
distributed. Some households spend nothing, while others might
spend more than $100,000 per year. In new research, we find
that the costs are even more skewed when accumulated over many
years, because some people with dementia can be in a nursing
home for 5 years or even longer. The accumulated costs can be
financially devastating to some families.
    In a second extension, because of the great importance of
long-term care in the total cost of dementia, RAND is
developing a report to be released this year that aims to help
providers, payers, and policy makers efficiently improve long-
term care for dementia.

                           PREPARED STATEMENT

    In summary, dementia is already very costly and will grow
even more costly. Clearly, medical breakthroughs that would
prevent or delay onset are urgently needed, but even in the
absence of such breakthroughs, innovations and policies that
can reduce costs should be pursued.
    Thank you, Mr. Chairman, and Ranking Member. Thank you for
your attention, and I look forward to your questions.
    [The statement follows:]
                 Prepared Statement of Michael D. Hurd
    Chairman Harkin, Ranking Member Moran, and members of the
subcommittee, thank you for the opportunity to testify before you today
about the monetary costs of dementia in the United States. My testimony
will be based upon research performed at the RAND Corporation and the
University of Michigan by me, and Professors Paco Martorell, Adeline
Delavande, Kathleen Mullen, and Kenneth Langa. It was published in
April, 2013 in the New England Journal of Medicine last year.
                  introduction: dementia and its costs
    Dementia, a chronic disease of aging characterized by progressive
cognitive decline that interferes with independent functioning, affects
a large and growing number of older adults. The National Alzheimer's
Project Act seeks to improve the ability of the Federal Government to
track monetary costs incurred by individuals and public programs, such
as Medicare and Medicaid, that result from dementia. We believe that
our research will contribute to that effort.
    Our goal in this research was to estimate the monetary costs due to
dementia, not the monetary costs of people with dementia. Accurately
identifying the costs attributable to dementia is challenging for many
reasons but two stand out: First, persons with dementia are likely to
have co-existing health problems: Insulating the costs attributable to
dementia requires that they be separated from other concurrent
healthcare costs. Second, informal caregiving, the unpaid care provided
by family and friends for assistance with activities of daily living,
is an important component of the support required by persons with
dementia, yet it is unclear how to attribute a monetary cost to an
informal caregiver's time.
                     data available for estimation
    The complexities of the research made it difficult to find valid
and reliable data that were adequate for our needs. Fortunately the
National Institute on Aging, under the leadership of Dr. Richard Hodes
and Dr. Richard Suzman, had the foresight many years ago to invest in a
data infrastructure, the Health and Retirement Study (HRS), without
which this research could not have been accomplished. The HRS is a
longitudinal survey; that is, it interviews repeatedly the same
individuals over time, about 20,000 persons over the age of 50 every 2
years in the case of the HRS. The HRS was first fielded in 1992 and
since then has become the pre-eminent data source for population-
representative studies of aging. Funded by the National Institute on
Aging and the Social Security Administration, it provides a wide
variety of longitudinal data on persons, including cognitive
assessments and data on the need for assistance in activities of daily
living as well as on healthcare and other costs. However, the HRS does
not have a direct measure of dementia, but such a measure is available
through the Aging, Demographics, and Memory Study, or ADAMS. The ADAMS
is study of a nationally representative sub-sample of 856 HRS
respondents who underwent a detailed in-home clinical assessment for
dementia. Using the diagnoses of the ADAMS subjects, we constructed a
statistical model to identify the probability that some 6,000 HRS
respondents over the age of 70 had dementia.
    We assessed several categories of healthcare spending: Out-of-
pocket spending, spending by Medicare, net nursing-home spending, and
formal and informal healthcare spending. Out-of-pocket spending
includes any out-of-pocket healthcare expenses for nursing-home or
hospital stays, medical visits, outpatient surgery, home healthcare,
special services such as outpatient rehabilitation, prescription drugs,
and dental services. Medicare spending is available for HRS respondents
who agreed to the linkage of their Medicare records and who were
enrolled in fee-for-service plans, or approximately 70 percent of
persons in our study population. Net nursing-home spending
distinguished between rates paid by Medicaid and those paid by third
parties. Formal healthcare includes paid care in home. Informal care
includes unpaid care in home, most often provided by family members.
              individual prevalence and costs of dementia
    Overall, we found 14.7 percent of the population 71 years of age or
older had dementia in 2010. Nonwhite, female, single, less-educated,
and lower-income persons have an elevated probability of dementia, as
do persons with a history of stroke, heart disease, or psychiatric
conditions. Those who did not graduate from high school were more than
twice as likely as those who graduated from college to have dementia,
and those with household income of less than $15,000 were more than
four times likely to have dementia as those with household income more
than $75,000.
    We distinguish between costs that flow through the marketplace such
as spending for hospital stays, doctor visits, nursing homes, hired
caregiving at home and so forth, and implicit additional costs that are
due to informal care and result from caregivers withdrawing from the
labor market. We found that persons with dementia had $33,329 more in
annual healthcare costs that flow through the marketplace than persons
without dementia. Adjusting for coexisting conditions and demographic
characteristics reduced this estimate to $28,501. This is the average
annual market cost attributable to dementia. Of the $28,501 in costs
attributable to dementia, $13,900 is for nursing-home care, $6,200 is
for out-of-pocket expenditure, $5,700 is for formal home care; Medicare
spent $2,700 of the total.
    We were not able to distinguish costs due to Alzheimer's disease
from costs due to other types of dementia, but we know from other
research that Alzheimer's disease is responsible for a large majority
of dementia cases.
    Adding the cost of informal care to the cost of market-based care
increases the total annual costs due to dementia to $41,685 per person
with dementia when based on the value of foregone wages. These costs
would be $56,290 per person with dementia when based on the valuation
of replacement cost for the informal care. Put another way, the value
of informal home care represents 31 percent to 49 percent of the costs
attributable to dementia, depending on how such care is valuated.
                 population-wide costs and projections
    To estimate the total cost of dementia to the U.S. economy now and
in the future, we combined the adjusted cost per person with dementia
with prevalence rates from the ADAMS and population estimates and
projections from the U.S. Census. Multiplying the per-person costs for
dementia by the estimated number of persons with dementia who were 71
years of age or older in 2010 indicates an annual population cost of
$109 billion for care purchased in the market. Including the estimated
value of informal home care boosts this estimate to a range of $159
billion to $215 billion. The cost for care purchased in the market
place ($109 billion) places dementia as the most costly disease in
terms of actual spending in the United States: According to tables
based on the Medical Expenditure Panel Survey published by the Agency
for Healthcare Research and Quality, heart disease cost $102 billion in
2010 (adjusted from $96 billion in 2008) and cancer cost $77 billion in
2010 (adjusted from $72 billion in 2008). Because neither heart disease
nor cancer is likely to require the large amount of informal care that
is required by dementia, accounting for informal care would increase
the cost difference between dementia and those diseases even further.
    Because of the aging of the population, the fraction of the
population at advanced old age where the risk of dementia is greatest
will increase. By 2040, assuming that prevalence rates of dementia at
each age remain the same, our estimates suggest that the costs for care
purchased in the market place will more than double from $109 billion
to $259 billion in real terms. Adding in the cost of informal care
places the cost in 2040 from $379 billion to $511 billion, depending on
the method for valuing informal care.
           differences from other estimates and possible bias
    A critical assumption in our estimates was that real costs per case
will remain constant. This may be likely for care-giving, because wages
of workers likely to provide care have remained stable or even
decreased in real terms. It is less likely, however, for healthcare
spending such as that for hospital costs or medication costs. To the
extent such costs continue to rise we may be underestimating future
costs of dementia. However, the amount of bias may be relatively small
because between 75 percent and 84 percent of attributable costs are for
care-giving, which has not been subject to the large increases in
prices of healthcare services.
    Our cost estimates are considerably lower than those reported by
the Alzheimer's Association, which estimated that annual monetary costs
alone were $172 billion in 2010, compared with our estimate of $109
billion. There are several reasons for this difference. The Alzheimer's
Association estimate of cost per case was higher than ours, but it was
based on a more severely impaired population. Its estimated prevalence
of dementia, which was higher than ours, was derived from a different
population than the population that produced the cost per case.
Prevalence came from a study of three Chicago neighborhoods. In that
study the diagnostic criteria for dementia did not require the presence
of a limitation in activities of daily living, as the ADAMS does,
likely explaining why prevalence was higher. Finally, its cost estimate
was not adjusted for coexisting conditions, as ours was.
                            future research
    Considerable future research remains to be done on this topic. We
did not address the distribution of costs, that is, who is likely to
pay the costs of dementia, particularly at the household level. Most
households will not incur large costs for dementia care: many patients
will have their care covered by Medicaid or private long-term care
insurance. Their nursing-home or hospitalization stays may be short and
relatively affordable, or households will avoid serious hardship for
some other reason. However, other households may face great costs
because of nursing-home stays of 5 years or more. In new, ongoing
research we found that when out-of-pocket spending for nursing homes is
aggregated over time, the distribution of costs is highly skewed
because of those very long nursing home stays. Thus, a minority of
families may face financially devastating costs. Research is needed to
quantify the distribution of costs so that families will have a better
understanding of the risks.
    Such research will also clarify the role of long-term care
insurance. This situation in which many families incur minor costs but
a few incur very large costs ought to call for an insurance solution,
one in which the costs of long-term care could be spread across the
entire population rather than being concentrated on the unlucky few. At
the moment the long-term care insurance products that are available
apparently do not meet the needs of the older population as evidenced
by the very low take-up rates, about 13 percent in the population age
55 or older. Better designed products to reduce the risk of very large
out-of-pocket spending for long-term care would help reduce a
significant cause for concern of the older population.
    Because a large majority of costs due to dementia are for long-term
care, supported by a grant from a private donor, RAND is developing a
report to be released this year that aims to help providers, payers and
policy makers efficiently improve dementia long-term care.
                            research funding
    This research on the costs of dementia was funded by a peer-
reviewed grant from the National Institute on Aging.
                                 ______

    The opinions and conclusions expressed in this testimony are the
author's alone and should not be interpreted as representing those of
RAND or any of the sponsors of its research. This product is part of
the RAND Corporation testimony series. RAND testimonies record
testimony presented by RAND associates to Federal, state, or local
legislative committees; government-appointed commissions and panels;
and private review and oversight bodies. The RAND Corporation is a
nonprofit research organization providing objective analysis and
effective solutions that address the challenges facing the public and
private sectors around the world. RAND's publications do not
necessarily reflect the opinions of its research clients and sponsors.

    This testimony is available for free download at http://
www.rand.org/pubs/
testimonies/CT406.html.

    Senator Harkin. Thank you very much, Dr. Hurd.
    Now we'll turn to Mr. Seth Rogen.
    Mr. Rogen, welcome, and please proceed.
STATEMENT OF SETH ROGEN, STAND-UP COMEDIAN, ACTOR,
            PRODUCER, DIRECTOR, SCREENWRITER, VOICE
            ACTOR
    Mr. Rogen. Thank you very much for having me, Mr. Chairman,
Ranking Member Moran, and the members of the subcommittee.
Thank you for the opportunity to testify today and for the
opportunity for me to be called an expert at something, because
that's cool.
    I don't know if you know who I am at all. You told me you
never saw ``Knocked Up,'' Chairman.
    So, it's a little insulting.
    It's very important, guys.
    Senator Harkin. I want the record to note this is the
first--I will wager this is the first time in any congressional
hearing in history, that the words ``knocked up'' have ever
been uttered.
    Mr. Rogen. Oy. You're not going to like the rest of this,
then.
    First, I should answer the question I assume many of you
are asking. Yes, I'm aware this has nothing to do with the
legalization of marijuana.
    In fact, if you can believe it, this concerns something
that I find even more important.
    I started dating my wife Lauren 9 years ago when her mother
was almost 54 years old. The first time I met her parents,
being the mensch that I am, I was excited to spend time with
them and make Lauren think I was the type of guy she should
continue dating.
    It was this trip, the first time I met my now-mother-in-
law, that Lauren first admitted to herself, and then to me,
that something was off with her mother. I guess the clues were,
unfortunately, easy to spot since both of Lauren's mother's
parents had Alzheimer's disease. Soon after this trip, at 55
years old, Lauren's mother was diagnosed with early onset
Alzheimer's.
    Now, at this point, my impression of Alzheimer's was
probably what I assume most people's impression is. I thought
it was something only like really, really old people got, and I
thought the way the disease primarily showed itself was in the
form of forgotten keys, wearing mismatched shoes, and being
asked the same question over and over. This period, which was
the only way I'd seen Alzheimer's displayed on movies or
television, lasted a few years for Lauren's mom.
    After that, however, is when I saw the real ugly truth of
the disease. After forgetting who she and her loved ones were,
my mother-in-law, a teacher for 35 years, then forgot how to
speak, feed herself, dress herself, and go to the bathroom
herself, all by the age of 60. Lauren's father and a team of
caregivers dedicate their lives to letting my mother-in-law be
as comfortable as she can be. They would love to do more, but
can't, because, as you've heard, unlike any of the other top 10
causes of death in America, there is no way to prevent, cure,
or even slow the progression of Alzheimer's disease.
    Another thing I didn't realize until I was personally
affected was the shame and stigma associated with the disease.
It was before I was born, but I'm told of a time when cancer
had a stigma that people were ashamed by. Celebrities and other
public figures that were stricken would hide rather than be
voices of hope for people in similar situations. And although
it's turning, this is currently where we are largely at with
Alzheimer's disease, it seems like.
    And it's because of this lack of hope and shameful stigma
that my wife, some friends, and myself decided to actually try
and do something to change the situation. We started Hilarity
for Charity. Hilarity for Charity is a fund we have as a part
of the Alzheimer's Association to raise money to help families
struggling with Alzheimer's and support cutting-edge research.
    That's right. The situation is so dire that it caused me, a
lazy, self-involved, generally self-medicated man-child to
start an entire charity organization. It was through this that
we felt we weren't just complaining there was nothing to be
done, but actively taking steps to do something. Instead of
being disappointed that young people were so misinformed about
the reality of the disease, we've started to educate them.
    We recently started a college program that allows
university students to hold their own Hilarity for Charity
events, and in the months since it's started, 18 schools
nationwide had signed up to hold events. The fact that we
actually got college students to stop playing videogames and
volunteer their time is a huge accomplishment, especially
considering both Xbox One and PlayStation 4 came out this year.
I'm sure these people know what I'm talking about.
    I came here today for a few reasons. One, I'm a huge
``House of Cards'' fan. Just marathoned the whole thing, had to
be here.
    Two is to say people need more help. I've personally seen
the massive amount of financial strain this disease causes, and
if the American people ever decide to reject genitalia-driven
comedy, I will no longer be able to afford it. Please don't.
Therefore, I can't begin to imagine how people with more
limited incomes are dealing with this.
    As you've also heard, studies show that Alzheimer's and
related dementia is the most costly condition in the United
States. Yes, it's more costly than heart disease in a country
where, for a $1.29, you can get a taco made out of Doritos.
They're delicious, but they're not healthy.
    While death from other major diseases like heart disease,
HIV, and strokes continue to decline, deaths from Alzheimer's
have increased almost 70 percent in the last 15 years. Over 5
million Americans have Alzheimer's, and at this rate, in 35
years as many as 16 million will have the disease.
    The third reason I'm here simply is to show people that
they're not alone. So few people share their personal stories,
so few people have something to relate to. I know that if me
and my wife saw someone like me talking about this, it would
probably make us feel a little less alone.
    Americans whisper the word ``Alzheimer's'' because their
Government whispers the word ``Alzheimer's.'' And although a
whisper is better than the silence that the Alzheimer's
community has been facing for decades, it's still not enough.
It needs to be yelled and screamed to the point that it finally
gets the attention and the funding that it deserves and needs.
    I dream of a day when my charity is no longer necessary and
I can go back to being the lazy, self-involved man-child I was
meant to be. People look to their Government for hope, and I
ask that when it comes to Alzheimer's disease, you continue to
take more steps to provide some more.

                           PREPARED STATEMENT

    I would like to thank the committee again for the
opportunity to share my story and to voice my wholehearted
support for the continuing work that pursues a cure for
Alzheimer's disease. Thank you very much.
    [The statement follows:]
                    Prepared Statement of Seth Rogen
    Mr. Chairman, Ranking Member Moran, and members of the
subcommittee, thank you for the opportunity to testify today, and for
the opportunity for me to be called an ``expert'' at something, because
it makes me feel smart.
    I should first answer a question I assume many of you are asking:
Yes, I'm aware this has nothing to do with the legalization of
marijuana. In fact, if you can believe it, this concerns something that
I find even more important.
    I started dating my wife, Lauren, 9 years ago, when her mother was
almost 54 years old. The first time I met her parents, being the mensch
I am, I was excited to spend time with them and make Lauren think I was
the type of guy she should continue dating.
    It was this trip, the first time I met my now mother-in-law, that
Lauren first admitted to herself, and then to me, that something was
off with her mother. I guess the clues were unfortunately easy to spot
since both of Lauren's mother's parents, had Alzheimer's disease. Soon
after this trip, at 55 years old, Lauren's mother was diagnosed with
early onset Alzheimer's.
    Now, I think at this point, my impression of Alzheimer's was
probably what I assume most people's impression is. It was something I
thought only really old people got, and I thought that the way the
disease primarily showed itself was in the form of forgotten keys,
wearing mismatching shoes, and being asked the same question over and
over. This period, which was similar to how I'd seen Alzheimer's
displayed movies and TV, lasted a few years for Lauren's mom. After
that, however, is when I saw the real ugly truth of the disease. A side
I literally had never been exposed to even by hearsay or dramatization.
    After forgetting who she and her loved ones were, my mother in law,
a teacher for 35 years, then forgot how to speak, feed herself, dress
herself, and go the bathroom herself. All by the age of 60.
    Lauren's father and a team of caregivers dedicate their lives to
letting my mother in law be as comfortable as she can. They would love
to do more, but can't, because unlike any of the top 10 causes of death
in America, there's currently absolutely no way to prevent, cure, or
even slow the progression of Alzheimer's Disease.
    Another thing I didn't realize until I was personally effected, was
the shame and stigma associated with Alzheimer's. It was before I was
born, but I'm told of a time when cancer had a stigma that people were
embarrassed by. Celebrities and other public figures that were stricken
would hide rather than be voices of hope for people in similar
situations. This seems to be where Alzheimer's is today. And it's
because of this lack of hope and shameful stigma that my wife, some
friends, and myself decided to actually try to do something to change
the situation.
    We started Hilarity for Charity. Hilarity for Charity is a fund we
have as part of the Alzheimer's Association to raise money to help
families struggling with Alzheimer's and support cutting edge research.
    That's right. The situation is so dire that it caused me, a lazy,
self involved, generally self-medicated man-child to start an entire
charity organization. It was through this we felt that we weren't just
complaining there was nothing to be done, but actively taking steps to
do something. Instead of being disappointed that young people were so
misinformed about the reality of the disease, we've started to educate
them.
    We recently started a college program that allows university
students to hold their own Hilarity For Charity events, and in the
month since it started, 18 schools nationwide have signed up to hold
events. The fact that we got students to volunteer their time is a huge
accomplishment; especially considering both Xbox One and PlayStation 4
both came out this year.
    I came here today for a few reasons:
    One: this is a super cool story, and I'm a huge House of Cards fan.
    Two is to say, people need more help. I've personally seen the
massive amount of financial strain this disease causes, and if the
American people ever decide to reject genitalia driven comedy, I would
no longer be able to afford it. Therefore, I can't begin to imagine how
people with more limited incomes are dealing with this. Studies show
that Alzheimer's and related dementia is the most costly condition in
the United States. Yes. It's more costly than heart disease in a
country where for a $1.29, you can get a taco made out of Doritos.
    While deaths from other major diseases like Heart disease, HIV, and
Strokes continue to decline, deaths from Alzheimer's have increased
almost 70 percent in the last 15 years. Over 5 million Americans have
Alzheimer's and at this rate, in 35 years, as many as 16 million will
have the disease.
    The third reason I'm here, simply, is to show people they're not
alone. So few people share their personal stories, so few people have
something to relate to, I know that if me and my wife saw somebody like
me talking about this, we would feel less alone.
    Americans whisper the word Alzheimer's because their Government
whispers the word Alzheimer's. And although a whisper is better than
the silence that the Alzheimer's community has been facing for decades,
it's still not enough. It needs to be yelled and screamed to the point
that it finally gets the attention and the funding it deserves and
needs, if for no other reason than to get some peace and quiet.
    People look to their Government for hope, and I ask that when it
comes to Alzheimer's disease, you continue to take more steps to
provide even more.
    I would like to thank the committee again for the opportunity to
share my story and to voice my wholehearted support for continuing the
work that pursues a cure for Alzheimer's disease.

    Senator Harkin. Thank you, Mr. Rogen. That was great. That
was very, very good. Thank you, thank you.
    Although I'm sorry you had to unmask me; I'm really Kevin
Spacey in disguise. Not too many people knew that.
    Thank you all very much.
    I'll start out with Dr. Hurd. I'm pleased to see your
research was funded by the National Institute on Aging. You may
be aware, all of you, or maybe you're not aware, that some of
my colleagues in the House of Representatives hold a different
view of the role of NIH in health economic research.
    In fact, the House draft of last year's appropriations
bill, our counterpart, which they released but did not pass,
included language that would have precluded NIH from supporting
any health economics research such as what Dr. Hurd did.
    So, Dr. Hurd, as an economist researcher, how important is
NIH's support to your work? Are there other Federal grants you
could have applied for to get this study off the ground?
    Dr. Hurd. It's extremely important, I would say all-
important to my work. I'm the holder of several investor
investigator initiative RO1s and program projects, as well as a
center grant.
    The importance of NIH funding comes from its long-term, I
would say primarily from its long-term reach and also from its
multidisciplinary aspect. Our study involved cognitive
scientists, economists, gerontologists, and similar. That kind
of assembling of a team is not easy outside of the NIH
umbrella.
    The long-term reach, however, is extremely important. I
mentioned the HRS was the foundation for this study. It would
not have been possible without the HRS. The HRS began in 1992.
I was part of the original team assembling HRS. That kind of
sustained funding over many years, I think, does not happen
outside of NIH for this type of research. I mentioned the 1998
study, a similar example, where we laid the foundations for the
study that we published in The New England Journal, really in
1998 and pursued over many years.
    So I just don't think the kind of study that we did would
be feasible outside of the NIH. I don't know of an agency that
would support that kind of long-term study, as well as the
multidisciplinary aspects.
    Senator Harkin. I appreciate that. Now, we didn't do that
on this side. Bipartisanly, we didn't. But I just want to get
that out just so that people understand that and that,
hopefully, the House won't repeat that again this year.
    Representative Moore, as a former policy maker, and a
patient, is there anything you've personally experienced that
would change? Is there anything we need to better educate
primary care physicians on, number one? I'll ask two questions.
That was number one, Dennis.
    Secondly, you've spent a lot of time on this side of the
dias. Is there--if you were up here, what questions would you
ask of NIH? Is there anything that we didn't ask or something
that we didn't cover?
    Mr. Moore. I really think you have asked the appropriate
questions of NIH. I just think it's important that people in
this country understand that this is a disease that's affecting
more and more people. I had it in my family with my dad. So I
wasn't terribly surprised when I was diagnosed. I understand
there are some genetics involved. It's something you wouldn't
wish on anybody, but it happens.
    And I hope someday they will find a cure. But right now, I
just think as a nation we need to deal with this disease as
best we can, and I really, really, really appreciate the fact
that you're holding this hearing and trying to get more
information so you can do the right thing.
    Senator Harkin. Thank you very much, Dennis.
    Mr. Moore. Thank you.
    Senator Harkin. Mr. Rogen, I got to be honest.
    I was reading this last night very quickly. I was reading
through it, and I said, ``Hillary for Charity? Hillary?''
    Mr. Rogen. Yeah. I forgot the T, I think, yeah.
    Senator Harkin. I had to stop and go back and read that
again.
    Mr. Rogen. Exactly. It's a progressive program.
    Senator Harkin. So, tell us more about Hilarity for Charity
and why focus on young people?
    Mr. Rogen. We chose to focus on young people because they
are the ones who will be affected by this very soon. And there
seems to be almost zero acknowledgement of it in the world of
these young people. It seems to be something that's not of a
high priority.
    It seems to be something that people, again, think only
happens kind of naturally when people enter their 90s. And I
don't think people understand that it's not their grandparents
being affected, it's their parents being affected. And soon
enough, it's them being affected.
    I really just saw that firsthand and really felt that there
was a massive hole missing when it came to, you know, informing
young people about the reality of this disease. And it didn't
seem like a high priority anywhere globally to inform young
people about the disease. So we decided we should do it because
no one else seemed like they were going to.
    Senator Harkin. Good for you.
    Senator Moran.
    Senator Moran. Mr. Chairman, thank you very much. I don't
know that I'll ask Mr. Rogen any questions. I'm a dull, boring
person.
    And I would certainly be reticent to have a conversation
with you as a comedian. I was fully prepared to be shown up by
you, but it really bothers me that Senator Harkin is even
funnier.
    Mr. Rogen. That Kevin Spacey line was great, yeah.
    Senator Moran. So, I don't know whether I'll ask you a
question or not. I'll start it with Dr. Hurd.
    And this really probably is a question, perhaps for Dr.
Collins and his crew at NIH. As I was listening to Dr. Hurd's
testimony, it occurred to me that it would be useful for me to
understand whether the prevalence of Alzheimer's is increasing,
or is that just a factor of us living longer?
    I don't know the answer to that. But I assume that has
significant cost consequences. So do the costs--are you
expecting greater costs in the future as a result of longevity?
And then scientifically, on a research basis, has Alzheimer's
been with us to the degree that it is today into the past? It's
just that we now live longer and therefore--it's not that we're
physiologically changing, it's just that we lived longer and
therefore the evidence exists?
    I don't know whether that's a question for you, Dr. Hurd,
or not. But before I've forgotten my question, I wanted to make
certain that I got it in front of Dr. Collins.
    Dr. Hurd. I can say something about that in two ways. We
looked in our data to see if we saw any trend in prevalence
adjusted for age. So you're exactly right. One needs to be
quite careful about increased dementia due to increases in
aging of the population, from changes in dementia prevalence
holding age constant.
    The latter would be a very important finding because then
that would suggest that, as the population ages, we may see
less prevalence than had been forecast. Our forecasts are based
upon constant prevalence holding age constant.
    So, the question came up earlier about over the age of 90.
We estimate around 38.5 percent of those over the age of 90 are
suffering from dementia. We assumed that rate remained constant
to 2040 until it's the aging of the population, more people
reaching those ages, that caused the increase in overall
population prevalence and the increases in cost.
    We studied our data quite carefully whether we could see
any change in age-specific rates of dementia over time. We saw
a slight suggestion of that, but we're not ready to write a
paper on that until we really are quite certain about that.
    There was a recent study in The Lancet in England that
suggested a decline in age-specific prevalence of dementia,
quite a large decline in prevalence. I think before we would
want to take that and put that into a forecast, we would want
to have more examples of that from a wider range of
populations.
    But right now, I think, at least from our perspective, we
do not see any change in age-specific prevalence.
    Senator Moran. Doctor, we generally have been using the
word ``Alzheimer's,'' and you've been using the word
``dementia.'' Is there a distinction to be drawn here?
    Dr. Hurd. Yes. We used--our study was about dementia
because that's what our data would support. We had sub-
diagnoses of Alzheimer's, but the data, we didn't have enough
observations really to distinguish those.
    This is somewhat outside my area of expertise, but my
understanding is that there is somewhat of a blurring line
between many forms of dementia and Alzheimer's. The majority of
dementia is Alzheimer's, the great majority. But typically,
there will be vascular dementia in addition to Alzheimer's at
the same time.
    Senator Moran. Should we expect an announcement, another
study, or the results of another study from you related to
these topics?
    Dr. Hurd. We're working right now. We have an RO1 from NIA
to look at long-term care, the costs of long-term care and the
role of health insurance for long-term care, long-term care
insurance. Why do we not have a functioning long-term care
insurance market? It's very clear that the costs are highly
skewed, and this should be an insurable situation. But we don't
yet have a well-functioning market for that. And we've produced
one paper on that and will produce further papers.
    Senator Moran. Thank you very much.
    Mr. Rogen, I appreciate your work, Hilarity for Charity.
And so my comments are dull and boring, but it's really an
expression of gratitude. I appreciate your efforts to educate
and to communicate with young people.
    One of the things that I might suggest in that regard, and
in talking to young people, is we need to instill in American
young men and women the desire to pursue careers, degrees, and
education in science, research, and medicine. We need the next
generation of the doctors that were in the preceding panel. And
I just would encourage you, and maybe you have comments in that
regard, but to do everything that you can to instill in people
the desire that this is a noble calling worthy of a career.
    Mr. Rogen. Yeah. I would love to do that. But actually, I
think one of the most distressing things, honestly, I learned
today was talking to Dr. Hodes before the panel, just in the
little waiting room area.
    And he was explaining to me something that he touched on
here as he was talking, was how the funding for the research in
this area is so sporadic and inconsistent that people--and I
relate to it as just a young person who is pursuing a career--
people are discouraged from entering this pursuit because it's
not as financially stable as many of the other diseases that
are having great strides taken in, you know, conquering them.
    And I will do my best to encourage it. But again, I ask the
Government to create a situation financially where there's the
means for the people with ideas to actually do something with
them. I mean, what he told me, again backstage, was there's
people that come to us with ideas that could literally be the
thing that cures this disease. And what we have to tell them
is, ``There's a one in six chance of that getting funding.''
    And they probably take from that, ``Man, if I go focus on
heart disease, I'll make more money and I'll also save lives.''
But it's a more glamorous situation financially. Alzheimer's
just isn't a cool disease, unfortunately.
    And it's something that I think, you know, that was
honestly one of the most distressing things I heard today was,
even people whose natural instinct would be to pursue curing
this disease are discouraged from the financial landscape of
this profession.
    Senator Moran. Well, while you earn a living as a comedian,
you are a very effective lobbyist.
    Mr. Rogen. I'll do it. You give the means, I'll give you
the people.
    Senator Moran. I certainly noticed that although you will
find that it's, this request, this plea for constant increasing
of funding is one that we've made for a number of reasons. But
included in those reasons is the understanding that people who
are making decisions about what to do in their careers need to
know, whether it's Alzheimer's or any other disease, that NIH
funding is going to be there and there's an opportunity for
them.
    The uncertainty that Congress and the administration can
create in budgets and spending creates a real challenge as we
try to recruit young people to the professions.
    Mr. Rogen. And I think that mentality trickles down to
people my age, and just honestly, shows them that it's not that
high of a priority on a national level. And that's what we're
trying to change.
    Senator Moran. Thank you very much.
    Let me now visit with my former colleague from Kansas.
    Dennis, thank you very much for being here. I appreciate
you reminding me that I was at your father's funeral. I
remember his condition and the reminder of heredity in
Alzheimer's disease. My question to you is this: What is the
state of knowledge? What is it that we know? When you've been
diagnosed with Alzheimer's, what is it that they can tell you
to do to make the quality of your life better, to slow the
process?
    In other words, my impression would be that you would be a
typical patient who learns of a diagnosis and you've pursued, I
assume, all the opportunities to try to find things that make
life better over the course of your remaining life. What is it
that's out there that people can tell you, our healthcare
professionals and others that can tell you what you can do?
What does the Alzheimer's Association tell you to do to
accomplish that in your life?
    Mr. Moore. Basically, to take the medication that they've
diagnosed for me, and others, I think. And also to get some
exercise, which I try to do on a daily basis. And my wife very
much encourages me to do that. And I'm a smart husband: I say,
``Yes, dear.''
    Senator Moran. Very good. Some things we won't forget. It's
a good thing.
    Mr. Moore. Right, right.
    Senator Moran. Well, Dennis, again, I appreciate you and
your public service.
    Mr. Moore. Thank you.
    Senator Moran. The chairman had a long list of things that
you've done in our State. And I wish you and Stephene
absolutely all the very best. And it's very pleasing to me to
see you here not on your behalf, but on behalf of all the
people who sit in this audience and the thousands of Americans
and people around the world who have encountered the same
circumstance that you encounter.
    And the way that you're living your life, I believe, gives
others courage and hope. And I commend you and Stephene for
that tremendous addition to your life, another role to play,
and you're playing it very well.
    Mr. Moore. I thank you very, very much for those comments.
And I also thank you for conducting this hearing and learning
more about this and what we as a nation can do to better deal
with this situation of Alzheimer's, because millions and
millions of Americans, as you well know, are being affected by
this. Thank you very much.
    Senator Moran. You're very welcome.
    Mr. Chairman, thank you.
    Mr. Moore. Thank you, Mr. Chairman.
    Senator Harkin. Dr. Hurd, and maybe I need to get Dr. Hodes
in on this, too. I'm a little confused here a little bit,
listening to your response on this.
    In other words, is dementia getting more aggressive,
affecting more percent of the population? Or is there just an
increase in the number of people over 65 that were living
longer, so the incidence is more? Another way I guess I might
say that is, is there any data that we have from the past about
the prevalence of dementia, let us say, in someone who is 50 or
55, compared with what it is now? So, do we have a higher
percentage of our population affected by dementia?
    Dr. Hodes, maybe this is for you. I don't----
    Dr. Hodes. There is no evidence of an increase in the risk
of dementia at a given age. I think, as you were alluding to,
in past years there was so little awareness and specificity of
diagnosis and so relatively few people reaching an age that we
don't have accurate figures for that point. Certainly,
longitudinal studies are ongoing now. But there is at present
no evidence that there's an increase in the incidence of
Alzheimer's at a given age.
    Senator Harkin. So, the percent of the population, say at
age 55 or 60, that were diagnosed with dementia, say 50 years
ago, is about the same as it is right now?
    Dr. Hodes. Well, really, I think all I can really say is
there's no evidence of a change. Fifty years ago, we simply
didn't have the statistics to answer your question.
    Senator Harkin. But you said that--I thought you told me,
though, that it is about the same, that there hasn't been an
increase in prevalence.
    Dr. Hodes. I'm trying to be careful. We have no evidence
that there has been any change.
    Senator Harkin. Oh.
    Dr. Hodes. And I think if you were asking people, asking us
to speculate, we don't--we don't know of reasons for change.
    Now, there are, for example, vascular components to
dementia that are affected by hypertension. And since
hypertension is better controlled, we might have expected it to
made a difference.
    But the straightforward answer: Do we have statistics 50
years ago and now, comparable diagnostic means that would allow
us to answer your question? The answer is: We don't know.
    The studies that have been referred to, the population-
based studies in Health and Retirement Survey that were--as an
example--that are beginning now or began 10 years ago will tell
us in the future, 10 years, 20 years from now.
    Senator Harkin. I see.
    Dr. Hodes. We'll be able to answer your question when
you're here 20 years from now better than we can right now.
    Senator Harkin. I'm retiring next year, by the way.
    Thank you very much.
    Senator Moran. I do have a question for Dr. Hodes.
    Senator Harkin. Dr. Hodes.
    Senator Moran. Dr. Hodes, thank you. I just saw the word
``doctor'' in front of ``Hurd'' and just started asking medical
questions.
    Senator Harkin has asked the question that I was trying to
pursue better than I did. And if you took the 50 years away and
said 5 or 10, is there evidence that the disease is more
prevalent, the incident is changing, either increasing or
decreasing in a shorter period of time? Or again, we just don't
yet have the evidence, we've got to wait another 20 years?
    Dr. Hodes. We don't have sufficient evidence over time.
    Senator Moran. Now, do you want to comment in the
longitudinal study, HRS?
    Dr. Hurd. Yes. So in the HRS, we again looked at that. This
is the time period from about 2000 up to 2008, which is a very
short time period, and maybe saw a slight suggestion of
improvement in age-specific rate of dementia. But we want to
pursue that further because of some technical reasons. As I
mentioned, there was the study in Lancet that suggested an
improvement. But I would say right now that we don't know.
    But you have to have very consistent methods over a long
period of time. We have that in the HRS, but not a long enough
time period to be able to answer your question.
    Senator Moran. I think why I think this is important is
that part of it is the cost. When you analyze what the costs
are going to be, you need to know what the trend is. But also,
from the diagnosis or the cause, are there environmental
factors? I hadn't thought about high blood pressure. But that,
the increase of stress in life and higher blood pressure,
what's the consequence? And again, does that then have a
consequence on the disease we're trying to eradicate?
    Dr. Hurd. Absolutely. And as a part of the priorities
through the national plan is having in place means to do just
this sort of surveillance. So, the longest term success we
mentioned, preventing, delaying Alzheimer's disease, will need
to be reflected by monitoring these kinds of population
effects. To do that, we have to have such surveillance. Those
studies are now in place, and it's important we maintain them.
    So we see whatever our interventions, whether it's on blood
pressure or any other more specific approaches to treat or
prevent dementias, we can monitor the impact on the prevalence
of the disease, the risk of the disease in the general
population.
    Senator Moran. Thank you very much, Dr. Hurd. Thank you for
piquing my interest.
    And, Dr. Hodes, thank you for answering the question.
    Senator Harkin. I have a follow-up question for Dr. Hurd.
Let me find your testimony here again. Just a second. What did
I do with it? Here it is. On this study, something leaped out
at me. It was this: ``Those who did not graduate from high
school were more than twice as likely as those who graduated
from college to have dementia. And those with household incomes
of less than $15,000 were more than four times likely to have
dementia as those with household income more than $75,000.''
    What does that tell us? Four times?
    Dr. Hurd. So these are raw statistics in the population
over the age of 70.
    Senator Harkin. Okay. But why would income have any bearing
on whether someone gets dementia or not?
    Dr. Hurd. It has to do with the correlation between age and
income. Very old people have much lower incomes than younger
people. So within the age 70 and above, the poorest people are
the oldest people. And age is so highly correlated with
dementia status.
    Senator Harkin. What do you mean the poorest people are the
oldest people? Rich people live to be old, too.
    Dr. Hurd. Yes.
    Senator Harkin. They probably live longer because they are
better able to get help.
    Dr. Hurd. Yes, that's certainly the case. More wealthy
people live longer than poor people. It's a cohort difference.
People who are age 90 live through a period where their
earnings are substantially less than people who are age 70. So
when the 90-year-olds were 70, they were poorer than today's
70-year-olds. And so there's a relationship between income and
age that brings the relationship between income and dementia
into the quantitative aspect that you mentioned.
    Senator Harkin. But when I read that, when you say
household income less than $15,000 more than four times likely
to have dementia as household income more than $75,000, I would
assume that's at every stage, at 70, 72, 75, 80, 90. No? That's
not right?
    Dr. Hurd. That's not what is in that table. It's not
corrected for anything. For age in particular is the main
aspect that it's not corrected for. And of course, in our
research, we do correct for that. But in that particular table,
there is not that correction.
    Senator Harkin. I'm having trouble with this.
    Dr. Hurd. Ask Mr. Rogen.
    Mr. Rogen. I actually get it, I think.
    Senator Harkin. You get it?
    Mr. Rogen. I think I do, right?
    Senator Harkin. And Kevin Spacey doesn't.
    Mr. Rogen. Yeah, exactly. I know.
    Senator Harkin. All right. Tell me. Tell me what you think.
    Mr. Rogen. I think what he's saying is that older people
have less of an income, and therefore, if you're older, by
default you'll have less of an income. And therefore, if you
have dementia, odds are you're old. Which, odds are, means you
don't have much of an income, which supports those statistics.
    Senator Harkin. Thanks. Thank you, Dr. Rogen.
    Dr. Hurd. It's easier to see in education, where the older
population is much less educated. And so 90-year-olds have, on
average, education of less than high school. And so in that
table, education is highly related to dementia status simply
because the much-older population is much less educated.
    Senator Harkin. Okay. My mistake is thinking that this was
true at every level of age.
    Dr. Hurd. No. No.
    Senator Harkin. I understand now. I got that. I just
wondered why there would be that difference, and there's not. I
understand that.
    Well, thanks for clearing that up, again, Dr. Rogen.
    Mr. Rogen. Any time.
    Senator Harkin. You have a future at NIH.
    Or the RAND Corporation. I don't know which.
    Did you have anything else?
    Senator Moran. Only this, Mr. Chairman. Thank you very much
to these witnesses. Thank you to the earlier panel from NIH.
We're very grateful for you allowing us to have this hearing
today. And I found it very useful. I appreciate the folks here
in the audience and across the country who are observing this
hearing. We understand how important this issue is in a human,
very direct way. And we want to continue our efforts to work
together to find the cure and provide hope to the American
people.
    On a much more pedestrian matter, Senator Collins asks that
she have a statement be made part of our record. And I would
ask unanimous consent to accomplish her request.
    Senator Harkin. Without objection. So ordered. Also, I have
received a statement from Senator Durbin. His statement will be
inserted at this point as well.
    [The statement follows:]
             Prepared Statement of Senator Susan M. Collins
    Mr. Chairman, Ranking Member Moran, thank you for calling this
hearing to examine the tremendous personal and economic toll that
Alzheimer's disease takes on the individual, the family, and our
Nation.
    Like many families, mine has experienced the pain of Alzheimer's
many times. There is no more helpless feeling than to watch the
progression of this devastating disease. It is equally painful to
witness the emotional and physical damage inflicted on family
caregivers, exhausted by an endless series of ``36 hour'' days.
    In addition to the human suffering it causes, Alzheimer's costs the
United States more than $200 billion a year, including $142 billion in
costs to Medicare and Medicaid. This price tag will increase
exponentially as the baby boom generation ages. If nothing is done to
slow or stop the disease, the Alzheimer's Association estimates that
Alzheimer's will cost the United States an astonishing $20 trillion
over the next 40 years.
    It is estimated that nearly one in two of the baby boomers reaching
85 will develop Alzheimer's. As a consequence, chances are that the
members of the baby boom generation will either be spending their
golden years with Alzheimer's or caring for someone who has it. In many
ways, Alzheimer's has become the defining disease of this generation.
If we are to prevent Alzheimer's from becoming the defining disease of
the next generation, it is imperative that we dramatically increase our
investment in Alzheimer's disease research.
    Alzheimer's is costing the United States more than $200 billion a
year, yet we are spending less than three tenths of 1 percent of that
amount--an estimated $584 million in fiscal year 2013--on research. We
currently spend about $6 billion a year for cancer research, $3 billion
a year for research on HIV/AIDS, and $2 billion for cardiovascular
research, all worthy investments. Surely we can do more for Alzheimer's
given the tremendous human and economic price of this devastating
disease.
    Investments in research for other diseases have yielded tremendous
results: patients have access to new treatments, and death rates for
some diseases are decreasing. At the same time, mortality due to
Alzheimer's is escalating dramatically, and it stands alone among the
top ten causes of death in the United States without an effective way
to prevent it, cure it, or even slow its progression.
    There is promising research in the pipeline that holds great hope
for Alzheimer's patients and their families. The research community is
poised to make important contributions toward the treatment of this
disease through clinical trials and by investigating new therapeutic
targets.
    The Omnibus Appropriations bill for fiscal year 2014 takes an
important step forward by providing for a $100 million increase for
Alzheimer's disease research at the National Institute of Aging. I
believe, however, that we need to do more.
    The National Plan to Address Alzheimer's Disease, which was
authorized by the 2010 National Alzheimer's Project Act which I co-
authored with then-Senator Evan Bayh, has as its primary goal, to
``prevent and effectively treat Alzheimer's disease by 2025.'' To meet
that goal, the Chairman of the Advisory Council created by the
legislation says that we will need to devote $2 billion a year to
Alzheimer's research.
    I believe that increasing our Nation's spending on Alzheimer's
research to just 1 percent of what we are currently spending to care
for Alzheimer's patients is a wise investment. I have therefore joined
with my colleague from Minnesota, Senator Klobuchar, in introducing a
resolution declaring that the goal of preventing and effectively
treating Alzheimer's by 2025 is an urgent national priority. Our
resolution calls for a doubling of our investment in Alzheimer's
research in fiscal year 2015 and resolves that the Senate will develop
a plan to meet our ultimate goal of a $2 billion annual investment
within the next 5 years.
    Mr. Chairman, Ranking Member Moran, I know that you share my
commitment to finding a way to prevent and effectively treat
Alzheimer's by 2025. Thank you for all of your efforts, and I look
forward to working with you to meet that goal.
                                 ______

            Prepared Statement of Senator Richard J. Durbin
    Thank you Chairman Harkin for convening this hearing to raise
awareness around the health and economic impact of Alzheimer's disease
and the importance of biomedical research to prevent and treat
Alzheimer's.
    Alzheimer's is so much more than just memory loss. It is a
debilitating disease that only gets worse as it progresses. People
living with the disease often forget conversations, appointments, and
eventually forget the names of close friends and may no longer
recognize their spouse or their children. They struggle to recall the
words to identify objects, and eventually lose the ability to read and
write. Alzheimer's makes everyday activities like keeping track of
bills and cooking a meal extremely challenging and frustrating.
Although the disease develops differently for every person, it
eventually leads to loss of memory, thinking, and reasoning skills.
    Last year, approximately 450,000 people in the United States died
from Alzheimer's disease. Today, more than 5 million Americans are
living with the disease. And with a new person being diagnosed with
Alzheimer's every 68 seconds, the number of people with Alzheimer's
will rise to 16 million by 2050. If nothing is done to change the
trajectory of the disease, more people and families will suffer and
Federal spending on care will soar.
    In 2013, the Medicaid and Medicare costs for caring for those with
Alzheimer's disease was $203 billion. If we stay on this path, total
medical costs associated with Alzheimer's disease are expected to rise
to $1.2 trillion by 2050, an increase of more than 500 percent.
    The promise of conquering Alzheimer's disease will only be
fulfilled through sustained Federal investment into biomedical
research. After several years of flat funding and spending cuts, NIH
isn't able to fund all of the critical research that needs to be done.
The number of research grants NIH funds has declined every year since
2004. In 2012, NIH funded 3,100 fewer grants than in 2004. Currently,
less than 1 in every 5 qualified grant proposals to the NIH is awarded
funding.
    Disinvestment in NIH has a far reaching ripple effect that hurts
economic growth and local economies in every State. Every dollar in NIH
funding stimulates $2.21 in business activity that develops around
research, such as biotech companies that provide supplies, food
services and restaurants, building construction, and hiring support
staff. Stagnant funding for biomedical research is short-sighted. It
undermines everything we are trying to do for this country and delays
the medical discoveries that will lower medical costs and improve the
lives of people with Alzheimer's. But the true cost of inadequate
support for Alzheimer's disease research is the toll that it takes on
our loved ones.
    Janet Dever is 73 years old and was diagnosed with Alzheimer's
disease 5 years ago. She does her best to not dwell on the negatives or
sink into depression. But she says that the hardest part of the disease
is watching her family and friends suffer along with her. The part of
the disease that upsets her the most is that many people don't know how
to interact with her anymore, so they have stayed away. Janet and her
husband Bill aren't giving up. And we shouldn't give up either.
    Over the past few years, Congress and the Administration have
stepped up the Federal investment in Alzheimer's research. In 2010,
Congress unanimously passed the National Alzheimer's Project Act, which
created a national strategic plan, establishing goals and action steps
to combat the disease in the areas of research, care, support, and
public awareness. In 2012, the NIH dedicated an additional $50 million
for Alzheimer's research. I will continue to work to bolster our
national commitment to ensure investments are made in Alzheimer's
research.
    Last summer, I met with a research scientist in St. Louis, who was
confident that biomedical research is on the cusp of making
transformative discoveries for diseases like Alzheimer's, but he fears
that what will keep us from making those discoveries will not be lack
of knowledge, but lack of Federal funding.
    Now is not the time for stagnant support for biomedical research.
Now is the time to invest in NIH and promising research to develop
cures and treatments for Alzheimer's. The Federal Government can and
should play a leading role to ensure our Nation remains the leader in
biomedical research, supports economic growth rooted in research, and
saving lives and improving lives through medical innovations. I look
forward to working with my colleagues to ensure continued and strong
support for biomedical research and to improve the lives of people
impacted by Alzheimer's.

    Senator Harkin. And again, I just join with my friend and
my colleague, Senator Moran, in thanking you all. Again, thanks
for our great leadership at NIH.
    Dr. Collins, Dr. Hodes, Dr. Landis were here. Thank you for
your great leadership.
    And all of you who are here today, I know a lot of you came
a great distance. I just want you to know this is an issue that
we are serious about. And we've got to find the funding for it.
And we've got to make sure we have a steady stream of funding.
This up-and-down just can't continue.
    I was very happy that I was able to join years ago with
Senator Spector to double over 5 years the funding for NIH. But
since then, it's gone downhill. We can't do that. We got it up
in that plateau to think that's where we were going to go up
from there. And it didn't work out that way.
    So we need your presence here, but we need your presence
back in your home States and back in your congressional
districts, talking to your Members of Congress on both sides of
the aisle to let them know the importance of this and the
importance of the steady funding that we need for the National
Institutes of Health.
    So if you'll do that, I hope that our funding level this
year will reflect again the kind of increases that we had last
year. We'll do everything in our power to make that happen.
    Again, I thank all of you for your advocacy, and I
encourage you to keep strong in that advocacy.

                     ADDITIONAL COMMITTEE QUESTIONS

    This place, this Senate, this Congress, however much you
may read to the contrary in the newspapers and the media, it
does respond to you. It responds to our constituents. It
responds to the pressure. It responds to what people want us to
do. And so, if you want this to happen, if you want us to make
sure we get this good funding stream for NIH, you've got to
keep the pressure up.
    And if you'll do that, then I think that we will see the
way clear for great strides in getting to that point where we
can actually prevent, treat, and cure Alzheimer's. That's our
goal. We're going to get there.
    [The following questions were not asked at the hearing, but
were submitted to the Department for response subsequent to the
hearing:]
             Questions Submitted to Dr. Francis S. Collins
               Questions Submitted by Senator Tom Harkin
    Question. As you know, I fought hard to overturn the Bush
Administration limitation on stem cell research. At the time, there
were a lot of high expectations for stem cell therapies that we have
not yet seen come to fruition. Can you elaborate, for the record, on
the role and the importance of stem cells on Alzheimer's research
today?
    Answer. The study of human embryonic stem cells has been essential
in aiding researchers in the development of many of the methods,
technologies and molecular tools that subsequently enabled them to
generate induced pluripotent stem cells (iPSCs). iPSCs are adult skin
cells that have been genetically reprogrammed to an embryonic stem
cell-like state and are one of the most exciting areas of stem cell
research in Alzheimer's and other neurodegenerative diseases. NIH-
funded researchers have developed methods for turning iPSCs into
different types of neurons, and are using these neurons to study
disease mechanisms and test potential therapeutic drugs--all in a dish.
    Recognizing the potential of iPSCs as a tool to enhance drug
discovery and provide further insights into the cell biology behind
neurodegenerative diseases, NIH is supporting several groundbreaking
initiatives relevant to the application of iPSC technologies to
Alzheimer's and related dementias. For example, six studies are
currently active under a 2012 solicitation for research supporting
development of human iPSCs and other reprogrammed cells for aging and
Alzheimer's disease modeling. These include a study to generate and
characterize iPSCs and neurons from individuals with both familial and
non-familial forms of Alzheimer's; development of an in vitro model of
inherited Alzheimer's disease; and a study using iPSCs to study
Alzheimer's epigenomics. In a separate initiative, announced in 2013,
investigators will use iPSCs to determine the function of candidate
risk genes and genetic variants in order to identify new gene or
cellular networks and molecular targets underlying the etiology of the
disease. Applications have been received in response to this
solicitation and are in review. In addition, NINDS has established
consortia to develop and study iPSCs derived from patients with
neurodegenerative diseases, including frontotemporal degeneration, a
type of dementia related to Alzheimer's disease. Cell lines developed
by these consortia as well as several Alzheimer's disease cell lines
developed by other scientists are stored in the NINDS Repository at
Coriell and are being distributed to academic and industry scientists
all over the world.
    The therapeutic potential of iPSCs remains undetermined, and
considerable research is needed before these cells can be considered
for testing as experimental treatments of Alzheimer's or other
diseases. Currently, researchers must use viruses to introduce the
reprogramming factors into adult cells, and this process must be
carefully controlled and tested before the technique can be applied to
clinical studies in humans. In animal studies, the virus used to
introduce the stem cell factors sometimes causes cancers. Researchers
are currently investigating non-viral delivery strategies.
    Question. I have read about a new method of aging stem cells
rapidly so that late-onset diseases can be better understood. Prior to
this technique, we could create cells, but we would have to grow them
for 60 or more years to see what happens in age-induced diseases. I
read that a recently identified protein can age a cell in a matter of
weeks. Can you explain for the record this Sloan Kettering study and
give us an idea of what it might mean for research into spontaneous
Alzheimer's disease?
    Answer. In this study,\1\ investigators introduced a protein called
progerin, which is associated with premature aging syndromes (e.g.,
progeria), into induced pluripotent stem cells from Parkinson's disease
(PD) patients. The progerin accelerated the aging process of neurons
differentiated from the iPSCs, and the induced neurons manifested PD-
like pathology within several weeks--considerably more rapidly than
they otherwise would have.
---------------------------------------------------------------------------
    \1\ Miller et al. Human iPSC-based Modeling of Late-Onset Disease
via Progerin-induced Aging. Cell Stem Cell, December 2013.
---------------------------------------------------------------------------
    If this technique can be replicated with cells from Alzheimer's
patients, it could speed the pace of discovery by providing a renewable
source of neurons within a very short period of time. This could
facilitate basic discovery and provide a platform for rapid preclinical
testing of Alzheimer's drugs.
    Question. I am pleased to hear that genetic sequencing has become
so rapid that in just 4 years we've moved from identifying one genetic
marker to identifying eleven. We could not have imagined this even 10
years ago. Are there similar high throughput testing mechanisms for
compounds that could be identified as drug targets?
    Answer. NIH is continually working to develop new mechanisms and
techniques to speed preclinical testing of compounds for Alzheimer's
disease. For example, NIH-supported investigators recently used a yeast
model that produces toxic amounts of amyloid-beta, one of the disease's
pathological hallmarks, to screen approximately 140,000 compounds. They
found that a class of compounds related to the drug clioquinol, which
alleviates amyloid toxicity in a mouse model, also reduced toxicity in
the yeast model, suggesting that this strain of yeast may prove to be
an effective, efficient, and relatively inexpensive model for rapidly
testing potential interventions.
    In addition, NIH is currently soliciting research applications to
develop assays for high-throughput screening for potential therapeutic
small molecule compounds. Although this new initiative is not specific
to Alzheimer's disease, the National Institute on Aging--the lead
Federal program for Alzheimer's disease research--is participating, and
applications on Alzheimer's disease are encouraged.
    NIH also supports drug discovery and development through programs
such as the Blueprint Neurotherapeutics Program, which identifies
investigators who have promising small molecule compounds but lack
outside drug development expertise and infrastructure support and
allows them access to a virtual pharma network of contract research
organizations, technical and regulatory experts and project managers,
with extensive biopharma-industry experience. The long-term goal of
this program is to advance projects from medicinal chemistry
optimization through Phase l clinical trials and facilitate industry
partnership for their further development.
    Identification of drug targets for Alzheimer's disease is also a
high priority for NIH. For example, in response to input from the
international research community at the May 2012 Alzheimer's Disease
Research Summit 2012: Path to Treatment and Prevention, the NIH
released four Funding Opportunity Announcements (FOAs) for new projects
aimed at speeding up drug development and testing of new therapies,
including one FOA intended to stimulate interdisciplinary research
focused on the identification and preclinical validation of novel
therapeutic targets within molecular networks involved in different
stages of Alzheimer's disease pathogenesis. Three large projects have
been funded under this initiative, including a study to identify and
characterize therapeutic targets within the innate immune system; a
study to discover, characterize and validate complex molecular networks
and candidate genes that influence susceptibility to cognitive decline
and Alzheimer's disease; and a study in which investigators will apply
innovative analytical methods to large-scale molecular, cellular and
clinical data from Alzheimer's patients to construct biological network
models and gain new insights into the complex mechanisms of the
disease.
    Finally, identification and characterization of biomarkers and
targets for intervention are the primary goals of the Accelerating
Medicines Partnership (AMP). Through the Foundation for the NIH, AMP
partners will invest more than $230 million over 5 years in the first
projects, which focus on Alzheimer's disease, type 2 diabetes, and the
autoimmune disorders rheumatoid arthritis and systemic lupus
erythematosus. For Alzheimer's disease, AMP resources will be used to
incorporate an expanded set of biomarkers into four ongoing trials
designed to delay or prevent disease, and to then evaluate which of
these biomarkers are most effective in reflecting the process of
disease and its response to intervention. AMP resources will also
support large-scale, systems biology analyses of brain tissue samples
from people with Alzheimer's disease to validate biological targets
that play key roles in disease progression in order to increase
understanding of molecular networks involved in the disease and
identify new potential therapeutic targets.
    Question. We talked a little about the BRAIN initiative, which the
recent Omnibus supported. As Dr. Collins mentioned, researchers have
made great strides in imaging techniques for Alzheimer's disease. Can
you explain how the BRAIN initiative is different than brain imaging
research NINDS has been doing in the past few years?
    Answer. The information from brain imaging research and from the
BRAIN Initiative are different, but they complement each other and will
ultimately come together to provide a more complete picture of how the
brain works and what goes wrong in diseases like Alzheimer's. Brain
imaging research has developed a powerful suite of non-invasive methods
for clinicians to diagnose and therefore treat brain disorders and for
researchers to study the living human brain in action. The various
types of imaging can reveal brain structure, activity, and even
biochemistry--for example, the accumulation of amyloid plaques that
characterize Alzheimer's disease or the loss of the signaling molecule
dopamine in Parkinson's disease. Brain imaging, however, is currently
limited in its resolution, both in space and time. At present, imaging
methods look at areas of the brain or nerve pathways that include
thousands or even millions of nerve cells, rather than at individual
cells, and average activity over seconds, while brain cells exchange
signals in milliseconds (thousandths of a second). The BRAIN
Initiative, in contrast, will develop methods that can resolve the
structure of individual nerve cells, nerve fibers, and synapses, that
is, the connections between cells, and can monitor activity of tens of
thousands of individual cells at the millisecond scale. This level of
detail is essential to understanding how nerve cells, precisely
connected in functional circuits, perform the computations that enable
us to perceive, think, and act.
    Another difference from brain imaging is that methods developed
through the BRAIN Initiative will not only allow investigators and
potentially clinicians to observe brain activity, but also to control
the activity of individual nerve cells. We have learned from years of
study in the simpler nervous systems of laboratory animals that
manipulating nerve cells' activity is essential to analyze how circuits
of nerve cells work. Optogenetics, for example, is a technology that
enables researchers to control cells' activity with light pulses in
experimental animals. As with brain imaging, methods now available to
stimulate the human brain affect large populations of cells. Even so
these methods can provide significant benefit for some diseases, such
as deep brain stimulation for Parkinson's. As understanding of brain
circuits advances and better methods become available to adjust their
activity, the application of these new tools and technologies should
provide better treatments for a much larger number of disorders.
    One of the six funding opportunity announcements that NIH released
for the BRAIN Initiative focuses on proposals for ``next generation''
human brain imaging that will go beyond incremental improvements in
existing technologies. This has the potential to have as transformative
an impact on brain science as next generation sequencing has had on
understanding the genome.
    Background.--Baby boomers are the offspring of a generation where
we saw the first group of long surviving family members with
Alzheimer's. Most baby boomers have, or will have, some exposure to
this illness, and they are concerned about their futures. They do not
want their children to have to take this on, and in some cases they are
aware that their children cannot take it on--financially or
emotionally.
    Question. Early-onset Alzheimer's has become a bigger issue now
that the baby boomers are contracting this illness in the prime of
their lives. Would you elaborate on the difference between early-onset
Alzheimer's and Alzheimer's or dementia? What are the symptoms and
long-term effects of having early-onset Alzheimer's vs. showing signs
later in life (55 vs. 80)? What are the survival rate differences? I
know I hear that some people that are diagnosed at 75 can live for
another 15-20 years.
    Answer. Early- and late-onset Alzheimer's disease share the same
characteristic pathologies (i.e., development of amyloid plaques and
tau tangles in the brain), and symptoms and disease course for early-
onset and late-onset patients are largely the same. For most patients,
memory problems are the earliest and most prominent symptom. However, a
subset of patients with early-onset disease will first experience non-
memory symptoms, including difficulties with language, visuospatial
skills, or executive function. These individuals also show distinctive
patterns of brain atrophy that are not seen in patients with late-onset
disease, and are less likely to carry the APOE-E4 genotype, which is
associated with Alzheimer's-related memory loss.
    Both early- and late-onset forms of Alzheimer's are associated with
a reduced life expectancy. Life expectancy after a diagnosis of
Alzheimer's disease can vary widely; some people live 20 years or more,
although this is unusual. In a recent NIH-supported study, among
participants over age 65 without dementia at baseline, individuals who
were diagnosed with the disease lived an average of about 4 years post-
diagnosis. Other sources place the average life expectancy for a newly
diagnosed patient at 8-10 years. Life expectancy is influenced by a
number of factors, including the patient's age at diagnosis, severity
of disease at diagnosis, and overall health.
    NIH-supported investigators have developed a tool physicians can
use to predict length of time from diagnosis to the need for full-time
care and to death. See http://www.cumc.columbia.edu/dept/sergievsky/
predictor.html.
    Question. We have entire generation of baby boomers that will
eventually face Alzheimer's or regular dementia. While the actual, out-
of-pocket, cost (not fees covered by insurance, Medicare or long-term
care insurance) of both of these illnesses will be expected to be taken
care of by the individuals and their families, how well will our
Country be prepared to handle these cases? Let's assume that baby
boomers, for the most part, are willing to assume the biggest costs--
over 55 housing, assisted living facilities, 24-hour caregivers, how
prepared will communities be? Will there be adequate facilities
available? Do we have the proper training and regulations in place for
their nursing care? (A concern I always hear is the turnover of
caretakers in private and public run facilities.) Are you finding that
young people want to pursue these kinds of careers? Are these factors
considered when you and your labs are researching Alzheimer's disease
and those affected?
    Answer. As you know, there is a growing demand for a health
workforce that is sufficiently prepared to meet the specialized needs
of an aging population. Within HHS, several agencies are charged with
ensuring that needs of this often vulnerable, underserved population
are met, including the Health Resources and Services Administration,
which focuses on bolstering the healthcare workforce to ensure that
adults living with Alzheimer's disease and dementia have access to the
care they need. HRSA supports several programs whose primary goal is to
improve access to quality healthcare for America's elderly by
addressing both the supply and education of geriatric specialties,
including Alzheimer's disease and dementia.
    We have found these programs to be successful in preparing our
communities to meet the needs of our aging population. For example, in
Academic Year 2012-2013, HRSA's Geriatrics Education Centers partnered
with over 650 healthcare delivery sites, including nursing homes,
chronic and acute disease hospitals, ambulatory care centers and senior
centers, across the country to provide clinical and experiential
training to over 25,000 student trainees. In addition, over 17,500
faculty-level trainees were trained on geriatric-related topics as a
result of these types of activities.
    Further, HRSA's National Center for Health Workforce Analysis
continues to analyze long-term care across the country. This analysis
will ultimately support a better understanding of how the Nation's
healthcare workforce can best meet the needs of our aging population
and inform the work of HRSA, NIH, and other agencies across the
Department that focus on geriatric and elder care.
    Question. Some independent labs are offering testing for
individuals that think they may be susceptible to Alzheimer's in their
future (due to family members, etc.), and there is talk concerning the
fact if Alzheimer's if treated early, possibly before the disease
really gasps the brain, that early drug treatment could help these
particular individuals. What do you say about that? Would you recommend
that people seek this kind of advance information? And, is it true that
early treatment might slow down the effects?
    Answer. The realization that the most effective way to treat and
prevent Alzheimer's disease may be to attack it early, before symptoms
begin, represents a watershed moment in the history of the disease.
Investigators have discovered that higher amounts of brain beta-
amyloid, the toxic protein that clogs the brains of Alzheimer's
patients and is associated with memory loss and other symptoms, is
related to an increased risk of developing dementia over time and to
loss of brain volume and subtle declines in cognitive abilities. These
findings suggest that brain beta-amyloid may in fact be a preclinical
sign of disease even among individuals who appear cognitively normal.
Other studies have shown that beta-amyloid may be present in the brain
for years--even decades--before clinical symptoms are evident, raising
the possibility that a ``window of opportunity'' exists to stop the
disease in its tracks before it has the opportunity to cause obvious
outward effects.
    However, we are just beginning to test preventive strategies,
including anti-amyloid therapies, in at-risk, pre-symptomatic patients,
and results from these studies will not be available for several years.
One very exciting such study is a 5-year clinical trial to determine if
an antibody treatment, crenezumab, designed to bind to and possibly
clear away abnormal amounts of amyloid protein in the brains of people
with Alzheimer's, can prevent decline in cognitive function. Crenezumab
will be tested among members of a unique and large family population in
Colombia sharing a genetic mutation known to cause observable signs of
Alzheimer's disease at around age 45. These individuals will be treated
at a time when abnormalities have appeared in brain images, but before
appearance of symptoms, when it may be possible to have an effect
before irreversible damage has occurred in neurons and their
connections. In another study, investigators are employing a similar
strategy of early intervention in testing an anti-amyloid drug in
cognitively normal older volunteers who are at increased risk of
developing late-onset Alzheimer's because they inherited two copies of
the APOE-E4 allele, the best known genetic risk for late-onset disease.
In addition, researchers on the Dominantly Inherited Alzheimer's
Network Trials Unit trial are testing new anti-amyloid-beta drug
treatments in volunteers who have an inherited form of Alzheimer's
disease. We anticipate results from the DIAN trial in 2016.
    The question of whether an individual should undergo testing to
assess risk for Alzheimer's disease is complex and highly personal, and
is best made in close consultation with that individual's healthcare
provider.
                                 ______

               Questions Submitted by Senator Jerry Moran
                           barriers to a cure
    Question. Alzheimer's disease currently has no cure, no diagnostic
test, and only symptomatic treatments. The Alzheimer's Disease Summit
mentioned several impediments to finding an Alzheimer's cure, including
the cost of bringing a potential treatment to market. Can you explain
the barriers preventing us from finding a cure for Alzheimer's disease?
    Answer. Alzheimer's disease is highly complex, with an imperfectly
understood etiology and an often complex underlying pathology. These
are some issues that have slowed our search for a cure.
  --A significant percentage of dementias is considered ``mixed,''
        i.e., it may combine Alzheimer's characteristic amyloid plaques
        and tau tangles, vascular pathologies, and other issues. This
        makes it difficult to know what, specifically, to target in the
        brain--or how to target it.
  --A major issue, and one that we are now addressing, is that previous
        trials may have been intervening too late in the disease
        process to be effective. Biomarker studies have shown that
        Alzheimer's pathology may be present in the brain literally for
        decades before symptoms occur, and we're finding that by the
        time symptoms appear in the clinic, it may be too late to
        intervene. For this reason, we've begun several major trials in
        individuals who are either asymptomatic but show Alzheimer's
        lesions on imaging, or who are at very high genetic risk. We
        have high hopes for this research and will report promptly and
        regularly on results.
    Question. Are you meeting the milestones set forth in the National
Plan to Address Alzheimer's Disease?
    Answer. NIH has been successful in meeting the initial milestones
established in the National Plan, and is well positioned to continue
meeting milestones in the immediate future.
    For example, the National Plan calls for the identification of
research priorities and milestones. NIH has taken the following steps:
  --Conducted the first Alzheimer's Disease Research Summit in May
        2012. The Summit was attended by an international group of some
        500 researchers, clinicians and members of the broader
        Alzheimer's community who worked together to identify research
        priorities and strategies needed to accelerate the development
        of successful therapies. A follow-up Summit is planned for
        2015.
  --Collected feedback on research needs and priorities through a 2012
        Request for Information.
  --Held the ``Alzheimer's Disease-Related Dementias: Research
        Challenges and Opportunities'' conference in May 2013 by NINDS,
        in collaboration with NIA and with support from several
        foundations (http://www.ninds.nih.gov/ADRD2013). This
        conference included an international group of experts that
        developed prioritized research recommendations to address AD-
        related dementias including frontotemporal degeneration, Lewy
        body disease, vascular and mixed dementias, as well as clinical
        diagnosis and health disparities in AD-related dementias.
  --Regularly updated the Plan to reflect evolving scientific
        opportunities and needs.
    Elsewhere, the Plan calls for the expansion of research aimed at
preventing and treating the disease. NIH activities in this area
include:
Strategy: Expand research to identify the molecular and cellular
        mechanisms underlying Alzheimer's disease, and translate this
        information into potential targets for intervention.
    Under several funding opportunity announcement (FOAs) issued in
response to the 2012 Summit, NIA has recently funded several major
projects responsive to this strategy:
  --Pathway Discovery, Validation, and Compound Identification for
        Alzheimer's Disease, a study to discover, characterize and
        validate complex molecular networks and candidate genes that
        influence susceptibility to cognitive decline and Alzheimer's
        disease.
  --Integrative Biology Approach to Complexity of Alzheimer's Disease,
        through which investigators will apply innovative analytical
        methods to large-scale molecular, cellular and clinical data
        from Alzheimer's patients to construct biological network
        models and gain new insights into the complex mechanisms of the
        disease. Several cellular and animal models will be used to
        validate the actions of individual genes, as well as entire
        molecular networks predicted to drive the disease.
  --A Systems Approach to Targeting Innate Immunity in Alzheimer's,
        which will use a systems biology approach to integrate genomic,
        gene expression, and pathological data from Alzheimer's
        patients and Alzheimer's mouse models and analyze them in novel
        ways with the goal of identifying and characterizing
        therapeutic targets within the innate immune system. The study
        builds on the genetic and pathological evidence that the innate
        immune system, which provides immediate defense against
        infection, and brain inflammation have a significant role in
        Alzheimer's disease.
Strategy: Expand genetic epidemiologic research to identify risk and
        protective factors for Alzheimer's disease.
    NIA is accelerating the search for genes involved in late onset
Alzheimer's disease (AD) through the AD Genetics Initiative. NIA is
stepping up the collection of a large bank of genetic material, cell
lines, and data from families with multiple members with late-onset AD
at the http://www.ncrad.org/. A case-control series also is being
developed. Qualified scientists will use the bank to search for the
remaining risk factor genes that contribute to late-onset AD, the most
common form of the disease. Scientists will share genetic data
developed from their research on an NIH-approved Web site, usually the
NIA Genetics of Alzheimer's Disease Data Storage Site or dbGaP.
Discovery of risk factor genes will help illuminate the underlying
disease processes of AD, open up novel areas of research, and identify
new targets for drug therapy.
    For a complete update on activities related to the National Plan,
please see http://aspe.hhs.gov/daltcp/napa/NatlPlan2014.shtml
    Question. A working draft of a report presented at the Alzheimer's
Disease Summit in November 2013 mentioned several impediments to
finding an Alzheimer's cure. The barriers include a lack of biomarkers,
finding appropriate people for clinical trials, and the lack of
partnerships with the private sector. How would you prioritize these
barriers and what is being done to overcome them?
    Answer. Each of these issues is significant, and NIH is taking
steps to address them. For example:
    Biomarkers.--NIH supports a number of initiatives aimed at
identifying and validating biomarkers for Alzheimer's disease. These
include:
  --The Alzheimer's Disease Neuroimaging Initiative (ADNI). This
        ambitious study began in October 2004 and was designed to find
        more sensitive and accurate methods to detect Alzheimer's
        disease at earlier stages and mark its progress through
        biomarkers. The study gathered and analyzed thousands of brain
        scans, genetic profiles, and biomarkers in blood and
        cerebrospinal fluid that are used to measure the progress of
        disease or the effects of treatment. In 2011-2012, data from
        ADNI facilitated the development of new diagnostic and
        neuropathologic criteria for mild cognitive impairment and
        Alzheimer's disease. Phase II of ADNI is currently underway to
        define changes in brain structure and function as people
        transition from normal cognitive aging to mild cognitive
        impairment (MCI--often a precursor to Alzheimer's) to AD.
  --The Biomarkers for Older Controls at Risk for Dementia (BIOCARD)
        study.--This longitudinal study was initiated in 1995 and uses
        repeated clinical evaluations, neuropsychological testing,
        neuroimaging, and fluid biomarkers to understand and predict
        progression from normal cognition to mild cognitive impairment
        (MCI) and to dementia, particularly Alzheimer's disease.
        Participants are cognitively normal individuals who were first
        degree relatives of patients with dementia.
    Encouraging Participation in Clinical Trials.--Insufficient
participant recruitment for research can delay or cause research study
cancellation, a substantial waste of resources. The need for
Alzheimer's clinical research study participants is particularly
urgent: Tens of thousands of volunteers are needed for research studies
focused on delaying, treating or preventing this growing public health
problem. To address this need, NIH has established several programs and
initiatives.
  --Recruiting Older Adults into Research (ROAR) Project.--Through this
        initiative, the Administration for Community Living, and the
        Centers for Disease Control and Prevention, the NIH, and their
        networks of state and community-based health and social service
        providers collaborated with researchers and private
        organizations to raise awareness, enhance knowledge and connect
        gatekeepers and older adults with easy, actionable
        opportunities for research participation. The cross-agency team
        established partnerships with existing government-funded
        resources and registries such as ResearchMatch, a free,
        national recruitment registry funded in part by NIH; the
        Alzheimer's Prevention Registry; and the Alzheimer's
        Association's TrialMatch service. The goal of the ROAR project
        is to significantly increase older adult enrollment in these
        registries, allowing for more targeted invitations to enroll in
        current and future research studies.
  --NIH Request for Information.--In 2012, the National Institute on
        Aging issued a Request for Information seeking input regarding
        strategies for increasing enrollment in Alzheimer's and related
        clinical trials. The Institute received approximately 20
        responses, which will inform recruitment activities going
        forward.
  --Outreach activities.--To help the public learn more about
        participating in clinical research, NIH created the resource
        ``NIH Clinical Research Trials and You''. The Web site includes
        personal stories from study participants, information about how
        to find a clinical trial, and educational resources for
        healthcare providers and the public. Among the materials
        included on the NIH Web site, as well as directly from the NIA,
        is the NIA fact sheet ``Participating in Alzheimer's Disease
        Clinical Trials and Studies'', which describes Alzheimer's
        disease clinical trials and studies, explains their scientific
        design, and offers key facts and questions to consider about
        volunteering for clinical research.
    Partnerships with the Private Sector.--NIH has successfully teamed
with private-sector partners on several initiatives, most notably the
Alzheimer's Disease Neuroimaging Initiative (see above). More recently,
NIH has established the Accelerating Medicines Partnership (AMP), a
bold new venture between the NIH, 10 biopharmaceutical companies and
several non-profit organizations to transform the current model for
developing new diagnostics and treatments by jointly identifying and
validating promising biological targets of disease. The ultimate goal
is to increase the number of new diagnostics and therapies for patients
and reduce the time and cost of developing them. Alzheimer's disease is
one of the first disease areas to be addressed through AMP. By
optimizing the process for identifying and validating clinically
relevant disease targets for drug design, AMP aims to increase
efficiency, improve the drug development process, and increase the
number and effectiveness of new targeted therapies.
    Question. Are these barriers specific to Alzheimer's?
    Answer. These barriers, while significant, are not specific to
Alzheimer's disease, and many of NIH's ongoing programs and initiatives
reflect this. For example, AMP will facilitate partnerships related to
type 2 diabetes, rheumatoid arthritis, and systemic lupus
erythematosus, in addition to Alzheimer's. The NIH Clinical Trials
Resource (discussed above) is not specific to Alzheimer's disease, and
in fact NIH supports a thriving communications and outreach
infrastructure that provides information and support to patients with
hundreds of diseases and conditions. Finally, identification of
disease-specific biomarkers is an important priority in a number of
disease areas, including neurological diseases and cancer.
           physical activity's effect on prevention/treatment
    Question. As we continue to search for a cure, there is promising
evidence physical activity may prevent or delay Alzheimer's disease.
However, it is my understanding that we are just scratching the surface
on how lifestyle factors such as diet and exercise can influence the
risk of developing the disease. At the University of Kansas Alzheimer's
Disease Center, research is ongoing related to the role of exercise in
preventing Alzheimer's disease. Could you explain the potential behind
this research path?
    Answer. The effect of exercise and physical activity on cognition,
including Alzheimer's disease, remains an area of intense scientific
study. Exercise benefits every organ of the body, improves sleep, and
promotes a sense of well-being. While the effects of exercise and
physical activity on cognitive health, including Alzheimer's disease,
have not been established in controlled studies, we do know that
exercise can help with weight control, which can be associated with a
decreased risk of cardiovascular disease and diabetes--both of which
are associated with a higher risk of Alzheimer's. Aerobic exercise also
improves oxygen consumption, which benefits brain function; aerobic
fitness has been found to reduce brain cell loss in older subjects.
People who have had overt strokes or ``silent'' strokes with no
apparent symptoms have an increased risk of developing dementia, and it
is therefore possible that exercise and other lifestyle interventions
that improve cardiovascular risk factors can reduce the risk of
dementia.
    Work continues in this important area. NIH-supported Alzheimer's
Disease Cooperative Study, a 70-member consortium of academic medical
centers and clinics that collaborate on the development of Alzheimer's
treatments and diagnostic tools, has recently initiated a randomized,
controlled trial to find out if supervised aerobic exercise can
influence cognitive decline, slow brain atrophy, or mitigate
Alzheimer's pathology in older adults with mild cognitive impairment
(MCI), a condition that often leads to Alzheimer's disease. Also, the
ongoing Lifestyle Interventions and Independence for Elders (LIFE)
study, a Phase 3 multi-center randomized controlled trial comparing a
moderate-intensity physical activity program to a successful aging
health education program in prevention of mobility disability among
sedentary older adults, will measure cognitive function as an outcome.
    Question. What are the strategies for the Alzheimer's Disease
Center network to continue building this type of research?
    Answer. The Alzheimer's Disease Center (ADC) Clinical cores enroll
subjects with normal cognition, mild cognitive impairment, and
Alzheimer's dementia. These subjects are then available to researchers
who may wish to study life-style factors such as exercise and nutrition
to investigate what role these factors may have in preventing cognitive
decline leading to MCI and AD. The life style studies are usually
funded by sources other than the Centers themselves but the Centers are
very useful because they provide research subjects and a rich
environment to support such research. A good example is the University
of Kansas ADC, where recruitment of subjects occurs through the center
and the exercise and nutrition studies are supported by R01 grants.
    Question. Do you plan to devote more resources towards this type of
research activity?
    Answer. The effects of exercise on cognitive decline and
Alzheimer's disease remains an important area of research, and NIH will
continue to support meritorious projects in this area as appropriate.
                            brain initiative
    Question. How have new technologies, for example brain imaging and
scans, helped identify people who may have Alzheimer's disease before
the actual symptoms occur?
    Answer. As recently as 10 years ago, definitive diagnosis of
Alzheimer's disease could only be made at autopsy. However, in 2004,
NIH-supported investigators developed the tracer compound Pittsburgh
Compound B (PiB) and demonstrated that it binds to amyloid-beta in the
brain, where it can be imaged using positron emission tomography (PET).
Several years later, investigators with the Alzheimer's Disease
Neuroimaging Initiative found that higher amounts of the protein
deposits in dementia-free people were associated with an increased risk
of developing dementia over time and with loss of brain volume and
subtle declines in cognitive abilities. These findings suggest that
brain beta-amyloid may in fact be a preclinical sign of disease even
among individuals who appear cognitively normal. Subsequent research
indicated that Alzheimer's pathology may be present in the brain
years--even decades--prior to diagnosis.
    In addition to imaging technologies, the use of fluid biomarkers to
diagnose disease and track treatment response has gained considerable
traction. ADNI investigators have also established a method and
standard of testing levels of both tau and amyloid-beta proteins in the
cerebrospinal fluid (CSF). They correlated levels of these proteins in
the CSF with changes in cognition over time and determined that changes
in these two protein levels in the CSF may signal the onset of mild
Alzheimer's disease.
    Scientists now are beginning to explore the combined use of
biomarkers and brain imaging to predict disease risk. A growing body of
research is devoted to looking for blood proteins whose levels change
during the early stages of Alzheimer's, which could lead to the
development of routine blood tests for risk assessment.
    Most of these early diagnostic tools and techniques are currently
only used in research and are not yet validated for use in clinical
practice. However, they may eventually facilitate clinical diagnosis of
the disease. Importantly, imaging and fluid biomarkers are increasingly
being incorporated into clinical trials as a means to track treatment
response.
    Question. How will the BRAIN Initiative help move research in
Alzheimer's forward?
    Answer. To find better treatments for Alzheimer's and other
intractable neurological disorders, we first need to gain a deeper
understanding into how normal circuits function and how the changes
wrought by these diseases impair the function of those circuits. For
example, in Alzheimer's disease, circuits reorganize as neurons die
off. Understanding how the circuits reorganize and how we might
intervene to optimize their function could help us develop new and
effective interventions for patients with Alzheimer's and related
dementias.
    Under the BRAIN Initiative, NIH has issued several research
solicitations that will enable us to develop a deeper understanding of
brain function through the creation of new tools capable of examining
the activity of millions of nerve cells, networks, and pathways in real
time. By measuring activity at the scale of circuits and networks in
living organisms, we can begin to translate data into models that will
elucidate how the brain encodes sensory experience, motor planning,
and, potentially, even memory, emotion, and thought.
    We believe that successful completion of the BRAIN Initiative will
revolutionize the field of neuroscience and set the stage for major
advances in Alzheimer's and other brain diseases.
                        fiscal year 2014 funding
    Question. The fiscal year 2014 Omnibus appropriations bill provided
a $100 million increase for research funding at the National Institute
on Aging. Can you please provide specific details on what research
activities this funding will go towards?
    Answer. In fiscal year 2014, the overall NIH appropriation was
increased to $30.15 billion (a 3.4 percent increase), while Congress
provided approximately $100 million in additional funding for the
National Institute on Aging (NIA), resulting in a budget increase of
12.5 percent for that Institute. In the Conference Report accompanying
the 2014 Consolidated Appropriations Act, legislators stated,
``Recognizing that Alzheimer's disease poses a unique and serious
threat to the Nation's long-term health and economic stability, the
Committee expects that a significant portion of the recommended
increase for NIA should be directed to research on Alzheimer's . . .
The Committee encourages NIA to continue addressing the research goals
set forth in the National Plan to Address Alzheimer's Disease, as well
as the recommendations from the Alzheimer's Disease Research Summit
2012.''
    Consistent with this language, NIA plans to use these additional
funds to support Alzheimer's research in areas of strategic priority
and scientific priority. Specifically, in fiscal year 2014, NIA will
fund additional awards to applications received from Funding
Opportunity Announcements issued in fiscal year 2013 (the President's
Alzheimer's initiative) and fiscal year 2014.
    These additional appropriated funds are added to our base (unlike
the one-time funds added by the NIH Director in fiscal year 2012 and
fiscal year 2013), so the NIA's fiscal year 2014 budget will be
estimated from this increased base. NIA is distributing these funds
among single-year and multi-year projects to maintain a stream of new
competing dollars to support high quality, peer-reviewed research on
aging and Alzheimer's disease in future years.
    Question. What types of research on Alzheimer's do you want to fund
in fiscal year 2015?
    Answer. The ongoing Alzheimer's disease (AD) research supported by
the National Institute on Aging (NIA) will continue in 2015, along with
several recently launched efforts made possible with increased funding.
These include:
  --Whole genome sequencing to identify new genetic variants that
        either increase risk (risk factors) or reduce risk (protective
        factors) for AD (in collaboration with the National Human
        Genome Research Institute).
  --A treatment trial to test the effectiveness of intranasal insulin
        in individuals with mild cognitive impairment or mild
        Alzheimer's dementia on cognition and daily functioning.
  --A 5-year prevention trial to test the ability of an antibody called
        crenezumab to bind to and clear away abnormal amounts of
        amyloid protein in the brain and prevent cognitive decline in
        people with early-onset AD.
  --Research to be funded in fiscal year 2013 and fiscal year 2014
        under four 2012 Funding Opportunity Announcements supporting
        drug discovery, development, and preclinical and clinical
        testing.
    We anticipate supporting new and ongoing activities in the
following areas in fiscal year 2015:
  --Additional Drug Development and Testing.--This will include support
        for drug repurposing and combination therapy, phase 2 (proof of
        concept) drug trials for agents against currently known
        therapeutic targets, and studies of possible agents against
        not-yet-known therapeutic targets for AD.
  --Non-Pharmacological Intervention Development.--We will focus on
        advancing non-pharmacological interventions for the cognitive
        and behavioral symptoms of AD and the design of approaches that
        combine pharmacological and non-pharmacological treatments.
  --Biomarkers of Disease Progression to Measure the Effects of
        Potential Treatments.--We will test imaging and fluid
        biomarkers for the assessment of disease-related pathology,
        work to develop and validate sensitive measures to detect and
        track the earliest clinical changes of AD, and develop and test
        methods for the standardization of neuroimaging procedures and
        data collection.
    Question. If funding were unlimited, how much would you commit to
Alzheimer's research?
    Answer. The infusion of new Federal funds to Alzheimer's research
in the past several years has accelerated the pace of discovery and
facilitated the support of research projects that may not otherwise
have been funded. It is also true that key findings in Alzheimer's may
come from unrelated (or loosely related) scientific areas, including
the new BRAIN initiative. Much of the research that we would support in
any year would be investigator-initiated that is, proposals from the
best scientists across the country, and budgeting for the creativity of
Alzheimer's researchers is, as I'm sure you can appreciate, an inexact
science, and not necessarily amenable to exacting cost estimates. It is
our expectation that as the field is stimulated by the additional funds
in fiscal year 2014 for NIA, there will be increased interest by both
investigators already involved in AD and related fields to apply for
support. In order to further stimulate the field, NIH has been through
an intensive planning process that has generated five priority RFAs,
which will be presented to NIA's Council for concept clearance in May.
While we cannot discuss the nature of the planned RFAs and their costs
until after concept clearance at NIA's May Council, we will do so for
the record after NIH Council Meeting.
                   vascular contributions to dementia
    Question. Studies have indicated that most people who die with
dementia have a combination of Alzheimer's and vascular disease
(stroke) and that vascular disease is the second leading cause of
dementia. What is the interplay between stroke and dementia?
    Answer. A recent article in the journal Neurology that highlighted
the burden of mortality from Alzheimer's disease pointed out that the
research community has embraced the concept of mixed dementia. In other
words, as you say, dementia most often arises from an interplay of
Alzheimer's disease and vascular causes. Brain vascular disease can
contribute to dementia not only through overt strokes, but also through
``silent strokes,'' which are not recognized from symptoms but are
apparent on brain imaging or examination of autopsied brains. Silent
strokes are very common--about 13 million people in the United States
have had silent strokes; twice as many have MRI scan evidence of
diffuse damage to the connecting fibers (diffuse white matter disease).
Studies show that these common consequences of chronic hypertensive
vascular disease are associated with dementia risk. Most importantly
these are modifiable by current treatments and recent reports of
decreased annual dementia risk from Europe may be related to better
vascular health. Therefore control of vascular risk throughout the
lifespan should be aggressively pursued not only to reduce heart attack
and stroke but also dementia.
    Brain vascular disease and dementia intersect at every level from
risk factors to molecular mechanisms. People who have had a stroke are
about nine times as likely to have cognitive impairment, and signs that
a stroke has occurred are often found in the brains of Alzheimer's
patients. Conversely, brain imaging studies suggest that people who
have brain protein aggregations characteristic of Alzheimer's disease
but have healthy brain vasculature are less likely to suffer dementia.
The Reasons for Geographic and Racial Differences in Stroke (REGARDS)
study, which is following more than 30,000 people, is one of several
epidemiological studies that have reported that high blood pressure and
other known risk factors for stroke increase the risk of cognitive
problems, even among people who have never had a stroke. At the
cellular and molecular level of analysis we are just beginning to
recognize the interrelationships between the mechanisms that underlie
Alzheimer's pathology and vascular problems. For example, beta-amyloid,
a key protein in Alzheimer's pathology, may stimulate the formation of
blood clots, which can cause stroke, and may have direct effects on the
integrity of blood vessels in the brain.
    The National Alzheimer's Disease Project Act recognized the
importance of Alzheimer's Disease Related Dementias, including vascular
dementia. In keeping with that, NINDS led a major planning effort, in
collaboration with the NIA and private groups, on these other
contributions to dementia. The NAPA Council has approved the
recommendations from that group.
                   accelerating medicines partnership
    Question. Which NIH Institutes and Centers will provide funding?
    Answer. National Institute on Aging (NIA), National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK), and National
Institute of Arthritis and Musculoskeletal and Skin Disease (NIAMS)
    Question. How much?
    Answer. NIA will contribute $67.6 million; NIDDK will contribute
$30.4 million; and NIAMS will contribute $20.9 million. These numbers
are over 5 years.
    Question. What research projects do you plan to fund with the
$129.5 million in total funding provided in this program for
Alzheimer's?
    Answer. The Alzheimer's disease proposal seeks to fund three major
clinical trials designed to delay or prevent disease onset.
Additionally, funds will go toward conducting a large scale analysis of
human Alzheimer's disease patient brain tissue samples to validate
biological targets previously shown to play key roles in disease
progression.
    Question. What is the 5-year budget plan for these funds?
    Answer. $4.4 million from industry x 5 companies = $22 million +
$67.6 million from NIH + $40 million in-kind contributions from
industry = $129.6 total.
    Question. How much funding will be expended in each year?
    Answer. Costs will be spread out approximately equally across the 5
years
    Question. Press reports indicate that other pharmaceutical
companies may be interested in the program in the future. Do you have
the ability to expand the pilot to include other companies?
    Answer. Yes. The partnership is fully formed and ready to get
started but organizations will likely keep joining and we hope and
expect there will be others. There is always a critical momentum effect
generated once a partnership like this is established.
    Question. Dr. Collins, could you please share with us the origin of
the idea for the Accelerating Medicines Partnership? Do you believe
drug discovery to be one of the most important investments for helping
control the rising costs of Alzheimer's care?
    Answer. It has become very clear in recent years that the
therapeutics development process is not efficient enough. We are seeing
extremely high attrition rates of safe, but ineffective therapeutics in
late phase clinical trials. In fact, failures due to insufficient
efficacy are responsible for 51 percent of Phase II failures and 66
percent of Phase III failures. This is costly in time and money and is
preventing the sector from focusing resources on the most promising
drugs. A major factor implicated in these failures is inadequate target
validation--the scientific process of identifying and verifying that a
specific molecule, if targeted by the right compound or drug, will
modulate disease progression. If the best targets were chosen earlier,
the late stage failure rate would decrease. And yet, despite the
challenges there is a great opportunity in science right now--our
knowledge of human biology is growing, DNA sequencing is getting
cheaper, and there is a real drive in the private sector to consider
target identification and validation pre-competitive and to work
together.
    Observing the challenges and the opportunity for a robust solution,
the NIH and industry began discussing these issues beginning in the
spring of 2011. In late 2011 NIH hosted a workshop with scientists from
all sectors to identify how the sectors could work together on this
problem. Following this workshop NIH and the industry partners
undertook a thoughtful planning process to understand the needs in this
area and how to design a partnership that could answer those needs. The
final characteristics of the program, with committed partners took
shape in the summer and fall of 2013, just months before the public
announcement on February 4, 2014.
    Question. Given your work in helping to promote genetic testing
technology, do you believe that consumers should have to wait until the
science is settled on the relationships between diseases, such as
Alzheimer's, and genetic or molecular markers before having access to
that information? Can the links ever truly be settled, or is better to
get patients genetic information to them when the patients want the
information? Could patients better informed on their own genetic
information be a link to help enable further research and education
even if what that information may mean is not fully understood?
    Answer. Your question is an important one. As you point out, in
some cases, the technology for genetic testing is out in front of the
evidence for the validity of a genetic test, that is, whether the test
accurately detects the presence of, or predicts the risk for, a
particular health condition. The best approach to genetic testing for
tests that predict the risk of a complex disease such as cancer or
Alzheimer disease is to consult with a genetics professional (e.g., a
genetic counselor, a physician who is board-certified in medical
genetics, or a nurse with specialized genetics training) before and
after testing. Before testing, a genetics professional can explain the
benefits, risks, and limitations of genetic testing. After testing, a
genetics professional can interpret the test results in the context of
a person's medical history, family history, the type of genetic test
(e.g., predictive vs. diagnostic), and the level of evidence for the
test's validity. Professional practice guidelines are also an important
resource to assess the validity of genetic tests.
    The NIH Genetic Testing Registry (http://www.ncbi.nlm.nih.gov/gtr/
), which provides detailed information about tests for more than 4,000
genetic conditions, links to practice guidelines that have been
developed for certain diseases and disorders. For example, tests for
Alzheimer disease link to practice guidelines from the American College
of Medical Genetics, the Agency for Healthcare Research and Quality,
and the European Federation of the Neurological Societies (see http://
www.ncbi.nlm.nih.gov/gtr/conditions/C0002395/). A list of practice
guidelines is available at https://www.ncbi.nlm.nih.gov/medgen/docs/
guideline/. NIH is committed to supporting research that establishes
the genetic contribution to health and disease and providing resources
that help patients and consumers make informed decisions about genetic
testing.
                                 ______

            Questions Submitted by Senator Richard C. Shelby
                     future of alzheimer's research
    Question. The National Alzheimer's Plan set forth an ambitious and
worthy goal of curing Alzheimer's disease by 2025. Do you think we will
reach this goal?
    Answer. The identification and development of interventions that
will prevent or treat Alzheimer's disease have proven to be extremely
challenging, and it is still not possible to predict with certainty
when an effective treatment or preventive intervention will be
available. However, we have greater reason than ever before to be
optimistic.
    Our efforts have been significantly advanced by recent
breakthroughs in biomedical imaging that are enabling us to identify
and track the earliest pathological stages of the disease process, long
before clinical symptoms are apparent. These discoveries, in addition
to discovery of other early biomarkers of the Alzheimer's disease
process, have opened a ``window of opportunity'' for us to target and
potentially reverse the disease's underlying pathology before
cognitive, behavioral, and emotional symptoms appear.
    NIH has begun to launch its first such clinical trials in
presymptomatic individuals. For example, in one study, investigators
are studying whether an antibody treatment, crenezumab, which is
designed to bind to and possibly clear away abnormal amounts of amyloid
protein in the brains of people with Alzheimer's, can prevent decline
in cognitive function among members a unique and large family
population in Colombia sharing a genetic mutation known to early-onset
disease. We anticipate initial results from this groundbreaking study
by 2017. In another study, the A4 Trial, will test an amyloid-clearing
drug in the pre-symptomatic stage of the disease, in symptom-free older
volunteers who have had positron emission tomography brain images that
show abnormal levels of amyloid accumulation. Positive results from
these or similar studies would provide important ``proof of concept''
that targeting preclinical disease is an effective strategy, and would
represent a major step forward in our efforts against Alzheimer's
disease.
    NIH also supports over 35 Alzheimer's disease clinical trials,
including a number of studies of interventions to slow disease
progression among individuals who are already showing symptoms. Over 40
compounds are currently under study to stimulate and advance research
on the discovery and development of new preventive and therapeutic
interventions for AD, mild cognitive impairment, and age-related
cognitive decline.
    Question. The Plan also set forth specific milestones. Are you
meeting them?
    Answer. NIH has been successful in meeting the initial milestones
established in the National Plan, and is well positioned to continue
meeting milestones in the immediate future.
    For example, the National Plan calls for the identification of
research priorities and milestones. NIH has taken the following steps:
  --Conducted the first Alzheimer's Disease Research Summit in May
        2012. The Summit was attended by an international group of some
        500 researchers, clinicians and members of the broader
        Alzheimer's community who worked together to identify research
        priorities and strategies needed to accelerate the development
        of successful therapies. A follow-up Summit is planned for
        2015.
  --Collected feedback on research needs and priorities through a 2012
        Request for Information.
  --Held the Alzheimer's Disease-Related Dementias: Research Challenges
        and Opportunities conference in May 2013 by NINDS, in
        collaboration with NIA and with support from several
        foundations (http://www.ninds.nih.gov/ADRD2013). This
        conference included an international group of experts that
        developed prioritized research recommendations to address AD-
        related dementias including frontotemporal degeneration, Lewy
        body disease, vascular and mixed dementias, as well as clinical
        diagnosis and health disparities in AD-related dementias.
  --Regularly updated the Plan to reflect evolving scientific
        opportunities and needs.
    Elsewhere, the Plan calls for the expansion of research aimed at
preventing and treating the disease. NIH activities in this area
include:
Strategy: Expand research to identify the molecular and cellular
        mechanisms underlying Alzheimer's disease, and translate this
        information into potential targets for intervention.
    Under several FOAs issued in response to the 2012 Summit, NIA has
recently funded several major projects responsive to this strategy:
  --Pathway Discovery, Validation, and Compound Identification for
        Alzheimer's Disease, a study to discover, characterize and
        validate complex molecular networks and candidate genes that
        influence susceptibility to cognitive decline and Alzheimer's
        disease.
  --Integrative Biology Approach to Complexity of Alzheimer's Disease,
        through which investigators will apply innovative analytical
        methods to large-scale molecular, cellular and clinical data
        from Alzheimer's patients to construct biological network
        models and gain new insights into the complex mechanisms of the
        disease. Several cellular and animal models will be used to
        validate the actions of individual genes, as well as entire
        molecular networks predicted to drive the disease.
  --A Systems Approach to Targeting Innate Immunity in Alzheimer's,
        which will use a systems biology approach to integrate genomic,
        gene expression, and pathological data from Alzheimer's
        patients and Alzheimer's mouse models and analyze them in novel
        ways with the goal of identifying and characterizing
        therapeutic targets within the innate immune system. The study
        builds on the genetic and pathological evidence that the innate
        immune system, which provides immediate defense against
        infection, and brain inflammation have a significant role in
        Alzheimer's disease.
Strategy: Expand genetic epidemiologic research to identify risk and
        protective factors for Alzheimer's disease.
    NIA is accelerating the search for genes involved in late onset
Alzheimer's disease (AD) through the AD Genetics Initiative, and is
stepping up the collection of a large bank of genetic material, cell
lines, and data from families with multiple members with late-onset AD
at the National Cell Repository for Alzheimer's Disease. A case-control
series also is being developed. Qualified scientists will use the bank
to search for the remaining risk factor genes that contribute to late-
onset AD, the most common form of the disease. Scientists will share
genetic data developed from their research on an NIA-approved Web site,
usually the NIA Genetics of Alzheimer's Disease Data Storage Site.
Discovery of risk factor genes will help illuminate the underlying
disease processes of AD, open up novel areas of research, and identify
new targets for drug therapy.
    For a complete update on activities with respect to the National
Plan, please see http://aspe.hhs.gov/daltcp/napa/NatlPlan2014.shtml
    Question. What advances in Alzheimer's research can we expect to
see in the next 5-10 years?
    Answer. The field is moving more rapidly than ever. In 5-10 years,
we would expect to see a much more comprehensive understanding of the
basic pathology of Alzheimer's disease and how it moves throughout the
brain. We should have a number of new therapeutic targets, as well as
new clinical trials in the pipeline. And, of course, we have every hope
that we'll have found something that delays, prevents, or slows the
progression of the disease.
                         traumatic brain injury
    Question. Repetitive concussions have been known to cause dementia
and, in particular, that Traumatic Brain Injury may increase a person's
risk for dementia. How common is this occurrence and what is the
connection with brain injury and dementia, particularly Alzheimer's?
    Answer. There is compelling evidence that frequently repeated blows
to the head can lead to dementia. First recognized in boxers as early
as the 1920s, this disorder, now called chronic traumatic
encephalopathy, or CTE, has been identified in the autopsied brains of
athletes from other sports, including football and hockey, and in the
brains of military veterans exposed to multiple head trauma. Although
we know that CTE occurs, and have begun to learn about its underlying
mechanisms in the brain, there are many unanswered questions, including
the important public health issue of how common CTE is and the
connection of less frequent mild traumatic brain injury (TBI) with
dementia in general.
    NIH is addressing these gaps in our knowledge. In September 2012,
the Foundation for NIH established the Sports and Health Research
Program with a generous donation from the National Football League. NIH
convened scientific workshops in December 2012 and July 2013 with
experts in CTE, Alzheimer's disease, and other dementias to discuss the
best pathways forward. Based on that guidance, NIH funded two
cooperative agreements, led by investigators at Boston University and
at Mount Sinai Hospital in New York City, that are focused on defining
the scope of long-term changes that occur in the brain years after a
single TBI or after multiple concussions. Among their activities, the
teams will also examine brain tissue for signs of CTE from elderly
participants of the NIA-funded ``Adult Changes in Thought'' study who
had a history of TBI at some time prior to death and brain tissues
collected by the NIH Neurobiobank from individuals who have died years
after a variety of TBI exposures. Neuropathologists in these projects
will also submit brain tissue with evidence of CTE to advanced brain
imaging teams who will attempt to identify a signature of CTE that
could be used to recognize CTE in brain scans of living people,
complementing promising developments in TBI brain imaging that are
already underway.
    To date, there is conflicting evidence and much uncertainty about
the important question, outside the extreme cases of professional and
high level amateur sports, of whether single or multiple TBIs increase
the likelihood that a person will develop Alzheimer's disease in later
life. Published reports have indicated that TBI can provoke changes in
tau and other proteins that have been associated with Alzheimer's
disease. For example, a recent article found that even a single TBI can
increase tau and amyloid beta, another protein characteristic of
Alzheimer's disease, many years later. Furthermore, any insult that
decreases ``cognitive reserve'' might be expected to affect cognitive
functioning in later life. Some epidemiological studies have found
evidence that there is indeed increased likelihood of developing
Alzheimer's disease among people who have a prior history of TBI.
However, other large epidemiological studies have not detected such an
association, so we do not yet have a definitive answer. Individual
differences in susceptibility, now under investigation for TBI, may be
part of the answer.
    Question. How are you collaborating with the Department of Defense
on this type of research?
    Answer. For many years, NIH has collaborated with the Department of
Defense, and also Veterans Affairs, on issues related to traumatic
brain injury (TBI), including long term consequences such as cognitive
problems. For example, NIH intramural investigators led a major long-
term study that followed the outcomes of TBI in Vietnam veterans. Over
the last several years, with the increasing concern about TBI in the
military, NIH and the Department of Defense have greatly enhanced their
interactions. NIH and the Department of Defense have held several joint
scientific workshops on topics including the neurological effects of
blast injury, emergency medicine for trauma, mild TBI diagnostics,
combination therapies for TBI, and TBI classification. The Department
of Defense was one of several agencies that came together with the
research community through the NINDS Common Data Elements (CDE) program
to agree upon standards for data collection that will allow meaningful
comparison across TBI studies in the United States and internationally.
The Department of Defense and NIH together led development of the
Federal Interagency TBI Informatics System (FITBIR), which provides a
common database for sharing of information among qualified researchers.
The Center for Neuroscience and Regenerative Medicine (CNRM) is a major
collaborative program that brings together Intramural NIH researchers
with those from the Uniformed Services University and Walter Reed
Medical Center. NIH leadership and program staff also participate on
grant and programmatic review panels and on advisory boards for the
Department of Defense and VA on research for TBI, and Departments of
Defense and of Veterans Affairs representatives are ad hoc members of
the NINDS Council. In 2013, as directed by an August 31st 2012, White
House Executive Order the Departments of Defense, HHS, VA, and
Education with OSTP developed a National Research Action Plan on PTSD
and TBI. The report presents strategies for enhancing the already
extensive inter-agency coordination and collaboration on TBI.
Workgroups across agencies are now implementing the research plan.
    Question. Have the brains of service members who have died from
Traumatic Brain Injury been part of any Alzheimer's disease research
studies to date?
    Answer. No. Not that we are aware. The Department of Defense has
not permitted examination of the brains of service members who have
died from blast injury, or who have died from suicide or other causes
after suffering blast injury. Currently there is no published
information on the effects of blast injury on the brains of service
members. In 2013, the Department of Defense funded the Chronic Effects
of Neurotrauma Consortium, which is designed to develop better
understanding of the linkage between combat-related TBI exposure and
later problems, including neurodegeneration. The Department of Defense
is also extending the NIH-led public-private partnership Alzheimer's
Disease Neuroimaging Initiative (ADNI) to include Vietnam veterans.
This project will examine the effects of TBI and PTSD on veterans using
brain imaging methods and biomarkers that the ADNI project developed
and validated. The Militarily-Relevant, Peer Reviewed Alzheimer's
Disease Program (MRPRA) has also focused on understanding the
relationship between TBI and Alzheimer's disease and on reducing that
burden. NIA and NINDS scientific experts have served as advisors on
these DOD programs, as appropriate.
                             drug approval
    Question. There are several FDA-approved drugs for Alzheimer's
disease, however none address the underlying disease itself. If we can
delay the progression of some of the symptoms and help memory and
cognitive thinking with treatment, why have we not found a cure? What
are the major obstacles?
    Answer. Alzheimer's disease is highly complex, with an imperfectly-
understood etiology and an often complex underlying pathology. Some
issues that have slowed our search for a cure include:
  --Presence of multiple pathologies--a significant percentage of
        dementias is considered ``mixed,'' i.e., it may combine
        Alzheimer's characteristic amyloid plaques and tau tangles,
        vascular pathologies, and other issues. This makes it difficult
        to know what, specifically, to target in the brain--or how to
        target it.
  --A major issue, and one that we are now addressing, is that may have
        been intervening too late in the disease process to be
        effective. Biomarker studies have shown that Alzheimer's
        pathology may be present in the brain literally for decades
        before symptoms occur, and we're finding that by the time
        symptoms appear in the clinic, it may be too late to intervene.
        For this reason, we've begun several major trials in
        individuals who are either asymptomatic but show Alzheimer's
        lesions on imaging, or who are at very high genetic risk. We
        have high hopes for this research and will report promptly and
        regularly on results.
    Question. I recently read about two breakthrough Alzheimer's
clinical trials funded by the National Institute on Aging and conducted
by the Alzheimer's Disease Cooperative Study. These two promising drugs
aim to prevent the disease itself. Can you discuss these two trials,
the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease Trial
(A4) and the Study of Nasal Insulin to Fight Forgetfulness (SNIFF)?
    Answer. The A4 (Anti-amyloid treatment in asymptomatic Alzheimer's
disease) secondary prevention trial will test an amyloid-clearing drug
in the pre-symptomatic stage of the disease, in 1,000 symptom-free
older volunteers who have had positron emission tomography brain images
that show abnormal levels of amyloid accumulation. Cognitive tests over
3 years are designed to determine if the drug is effective in
maintaining cognitive health, and imaging tests will track structural
and functional brain changes. The trial, which will also be supported
by private sector contributions, will provide important information
about the effectiveness of clearing amyloid from the brain in the early
stages of the disease and inform future prevention studies.
    The purpose of the SNIFF study is to find out whether a type of
insulin, when administered as a nasal spray, improves memory in adults
with a mild memory impairment or Alzheimer's disease. The rationale
behind the study is growing evidence that insulin carries out multiple
functions in the brain and that poor regulation of insulin may
contribute to the development of Alzheimer's disease. Insulin
resistance, reduced cerebrospinal fluid insulin levels, and reduced
brain insulin signals have been found in Alzheimer's patients,
suggesting that a therapy aimed at correcting these deficiencies may be
beneficial.
    Both studies are being carried out under the auspices of the
Alzheimer's Disease Cooperative Study, and both will be active in 2014.
                 down syndrome and alzheimer's disease
    Question. Research has indicated that studying individuals with
Down syndrome may help progress research on Alzheimer's disease. The
majority of Down syndrome individuals develop plaque in the brain and
over half of those with Down syndrome will suffer from the early onset
of Alzheimer's disease. But conversely, only half of those with
plaque--the hallmark of Alzheimer's--develop the Alzheimer's. Is NIH
researching this phenomenon?
    Answer. Researchers funded by the National Institutes of Health are
working on many fronts to explore the nexus of Alzheimer's and Down
syndrome (DS). Basic research aims to better understand the two
disorders' common genetic and biological underpinnings. Observational
studies are looking at young adults with DS to see if and how they
develop Alzheimer's. In addition, basic studies or epidemiological or
observational studies that help define risk factors or measure the
course of the disease are underway. Some studies seek to uncover the
specific molecular and genetic processes at work, while others follow
study volunteers with DS as they age to look for correlations between
brain changes and changes in cognition. An ongoing study funded by the
National Institute on Aging (NIA) is documenting amyloid deposition in
asymptomatic adults with DS and following these individuals to
understand the course of amyloid deposition and its effect on
functioning over time, while the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD) is currently
supporting a five-year study to identify how dementia develops in
adults with DS over age 35 by looking at cognitive-test results,
certain proteins in blood, and connections between brain regions
measured by a type of magnetic resonance imaging (MRI) called diffusion
tensor imaging.
    A few clinical trials are testing potential treatments; these
include a study of low-dose transdermal nicotine to slow cognitive
decline in DS patients with mild cognitive impairment and a study of
epigallocatechin-3-gallate, a compound found in green tea, to improve
cognitive performance and slow disease progression in DS patients with
Alzheimer's.
    In April 2013, the NIA co-sponsored a conference to help set a
research agenda aimed at speeding the development of possible therapies
to treat Alzheimer's in DS. Representatives from academia, industry,
Federal agencies, and private foundations explored topics such as the
Alzheimer's disease pathway, animal models, biomarkers, and cognitive
assessments. In September, NICHD launched the Down Syndrome Consortium
Registry, called DS ConnectTM. Through this dynamic resource, people
with DS, their family members, and others will be able to enter highly
secure profiles to access information about DS and, with their
permission, be contacted about opportunities to participate in
research.
                                 ______

              Questions Submitted by Senator Thad Cochran
             alzheimer's research for minority populations
    Question. Recognizing the devastating impact of Alzheimer's disease
and Alzheimer's Disease-Related Dementias on patients and families, and
also recognizing that the time was right--from both a scientific and a
public health standpoint--to move aggressively toward the development
of new and effective treatments for Alzheimer's, Congress passed the
National Alzheimer's Project Act (NAPA) in December 2010 and it became
public law on January 4, 2011. NAPA requires the HHS Secretary to
improve outcomes for ethnic and racial minority populations at higher
risk, among other requirements. The value of the diversity of
Mississippi's population for research is commonly unrecognized.
    Dr. Collins, your testimony indicates that one of requirements of
the National Alzheimer's Project Act is to improve outcomes for ethnic
and racial minority populations who may be at higher risk. How
important is it to ensure that we are expanding Alzheimer's research to
these unique and diverse populations, including in my home state of
Mississippi?
    Answer. Addressing disparities in Alzheimer's disease risk and
outcomes is a major priority for NIH, and a number of studies are
ongoing in this area. For example, research supported by the National
Institute on Aging aimed at elucidating risk and protective factors
among vulnerable populations includes the following:
  --In an ongoing study, researchers are working to identify genetic
        risk factors for Alzheimer's disease (AD) in a cohort of
        Hispanics of Caribbean descent.
  --The Chicago Health and Aging project is exploring several genetic
        and other risk factors for cognitive decline and AD in African
        American and non-Hispanic white participants, including the
        intersection of markers of inflammation, blood pressure, and
        other vascular factors with cognitive function.
  --A recently-completed study, initiated with funding from the
        American Recovery and Reinvestment Act, assessed the
        associations of over 900,000 genetic markers with cognitive
        decline among 7750 older African Americans and Africans.
  --Support from the American Reinvestment and Recovery Act has enabled
        the Health and Retirement Study (HRS) to conduct genotyping on
        approximately 20,000 participants and use these data to
        elucidate genetic influence on a number of parameters,
        including cognition. ARRA funds also facilitated the
        recruitment of additional minority participants, further
        strengthening the study's utility in identifying risk and
        protective factors in these populations.
  --The Alzheimer's Disease Genetics Consortium (ADGC) collaborates
        with the NIA-supported Alzheimer's Disease Centers to conduct
        large-scale genome wide association studies (GWAS) in search of
        risk factor genes for the disease. To provide insights into
        genetic risk and protective factors related to cognitive
        decline and dementia, the ADGC has leveraged a variety of
        existing epidemiologic, case-control, and family based data and
        sample sets, including African American and Hispanic cohorts.
    Minority populations, including African Americans and Hispanics,
have a higher risk than whites of both strokes and ``silent strokes,''
placing them at a particularly high risk for cognitive decline and
dementia. Recognizing the urgent need to address health disparities in
dementia, an entire session of our recent conference on Alzheimer's
Disease-Related Dementias (ADRDs) was devoted to health disparities.
This conference, which was convened as part of National Plan to Address
Alzheimer's, brought together internationally recognized experts to
develop a set of prioritized recommendations to guide scientific
research on AD-related dementias for the next 5 to 10 years, including
recommendations focused on increasing recruitment in clinical studies
and advancing treatment and prevention strategies among diverse
populations. The NAPA Council has approved these recommendations and
proposed that they should be included in the next version of the
National Plan to Address Alzheimer's.
    In another ongoing study, supported by the National Institute of
Neurologic Disorders and Stroke, investigators are studying the
hypothesis that Vitamin D deficiency may partially explain some of the
excess risk of cerebrovascular disease and cognitive decline in African
Americans compared to whites. This study, led by researchers at Johns
Hopkins University, has a performance site at the University of
Mississippi. A study to elucidate the relationship between depression
and cognitive decline, including Alzheimer's disease, is likewise
ongoing in Mississippi; this study is funded by the National Institute
of Mental Health. Finally, the National Heart, Lung, and Blood
Institute is supporting a number of studies in Mississippi dealing with
hypertension, diabetes, and cardiovascular disease, all of which
disproportionately affect underserved populations and all of which are
associated with an increased risk of Alzheimer's.
                   accelerating medicines partnership
    Question. Identification and characterization of targets for
intervention are the primary goals of the Accelerating Medicines
Partnership (AMP), just announced in February 2014. With project
management by the Foundation for NIH, ten pharmaceutical companies will
collaborate with NIH. All data will be made publicly available, and NIH
and industry will share in the $230 million cost over 5 years for the
first projects including Alzheimer's disease. For Alzheimer's disease,
AMP resources will be used to incorporate biomarkers into four ongoing
trials designed to delay or prevent disease, and then evaluate which
ones are most effective. AMP resources will also support analyses of
brain tissue samples from people with Alzheimer's disease in order to
increase understanding of the disease and identify new potential
therapeutic targets. AMP represents an unprecedented model for pre-
competitive collaboration that should accelerate the ability to
identify the next generation of drug targets and biomarkers.
    Dr. Collins, could you please share with us the origin of the idea
for the Accelerating Medicines Partnership? Do you believe drug
discovery to be one of the most important investments for helping
control the rising costs of Alzheimer's care?
    Answer. It has become very clear in recent years that the
therapeutics development process is not efficient enough. We are seeing
extremely high attrition rates of safe, but ineffective therapeutics in
late phase clinical trials. In fact, failures due to insufficient
efficacy are responsible for 51 percent of Phase II failures and 66
percent of Phase III failures. This is costly in time and money and is
preventing the sector from focusing resources on the most promising
drugs. A major factor implicated in these failures is inadequate target
validation--the scientific process of identifying and verifying that a
specific molecule, if targeted by the right compound or drug, will
modulate disease progression. If the best targets were chosen earlier,
the late stage failure rate would decrease. And yet, despite the
challenges there is a great opportunity in science right now--our
knowledge of human biology is growing, DNA sequencing is getting
cheaper, and there is a real drive in the private sector to consider
target identification and validation pre-competitive and to work
together.
    Observing the challenges and the opportunity for a robust solution,
the NIH and industry began discussing these issues beginning in the
spring of 2011. In late 2011 NIH hosted a workshop with scientists from
all sectors to identify how the sectors could work together on this
problem. Following this workshop NIH and the industry partners
undertook a thoughtful planning process to understand the needs in this
area and how to design a partnership that could answer those needs. The
final characteristics of the program, with committed partners took
shape in the summer and fall of 2013, just months before the public
announcement on February 4, 2014.
                     established research programs
    Question. Language was included in the fiscal year 14 Omnibus
Appropriations bill by the Committee urging NIH to take advantage of
existing, well-characterized, longitudinal, population-based cohort
studies in order to build upon the strong body of work already being
done in NIH-funded Alzheimer's Disease Research Centers. Mississippi
researchers currently participate in several already established
studies and we believe that it is worthwhile to continue this support.
    Dr. Collins, I was pleased my state of Mississippi was able to host
you at the University of Mississippi Medical Center in 2012 where we
recognized the Mississippi recipients of NIH's Institutional
Development Awards. Is it a priority for NIH to leverage previously
established research studies where significant Federal investments have
already been made in order to propel Alzheimer's research forward?
    Answer. NIH places a high priority on leveraging previously
established research, where appropriate. For example, hundreds of
studies have been initiated based on data from the NIH-supported
Alzheimer's Disease Neuroimaging Institute. In fact, ADNI's data-
sharing policy--data are freely available to any qualified researcher--
has stimulated the development of a worldwide Alzheimer's collaboration
among academia, government and industry researchers by making study
data publicly accessible and has resulted in over 350 published papers.
To date, nearly 2,500 researchers have signed up for ADNI database
access.
    Other NIH initiatives share ADNI's approach to data-sharing. In
fact, data from the Brain Research through Advancing Innovative
Technologies (BRAIN) initiative,, the Accelerating Medicines
Partnership (AMP), the National Institute on Aging Genetics of
Alzheimer's Disease Data Storage Site (NIAGADS), and the Database of
Genotypes and Phenotypes (dbGaP) are available to investigators
worldwide.
                                 ______

             Questions Submitted by Senator Lamar Alexander
    Question. You mentioned that the Alzheimer's Disease Neuroimaging
Initiative established methods and standards for testing biomarkers in
cerebrospinal fluid, and the Accelerating Medicines Partnership is
focused on incorporating an expanded set of biomarkers into four
ongoing trials. One concern I have is that some of the innovative
breakthroughs happening in this and other fields are not translating
into drug evaluation by the FDA.
    Have you worked with FDA on how these exciting biomarker
breakthroughs could be used as the basis of or evidence for drug
approvals? What barriers, if any, are there to working with FDA on some
of the advancements you have made with biomarkers and testing and using
that to shorten drug development?
    Answer. Through our involvement with the National Alzheimer's
Project Act (NAPA) Council and elsewhere, NIH is working closely with
the FDA to facilitate approval of drugs for Alzheimer's disease. In
February 2013, FDA released draft guidance for industry on developing
drugs for the treatment of early stage Alzheimer's; this draft guidance
specifically addresses the approval of drugs for Alzheimer's disease
based on the use of biomarkers. The draft guidance indicates that a
positive biomarker result in combination with a positive finding on a
clinical outcome measure may be used as evidence of drug efficacy.
However, the draft guidance also indicates that FDA will not be able to
consider an approval based on the use of biomarkers until there is
widespread evidence-based agreement in the research community that an
effect on a particular biomarker is reasonably likely to predict
clinical benefit. FDA's involvement in the Accelerating Medicines
Partnership also signals their commitment to work with NIH and others
on this important issue.
    Question. Given your work in helping to promote genetic testing
technology, do you believe that consumers should have to wait until the
science is settled on the relationships between diseases, such as
Alzheimer's, and genetic or molecular markers before having access to
that information? Can the links ever truly be settled, or is better to
get patients genetic information to them when the patients want the
information? Could patients better informed on their own genetic
information be a link to help enable further research and education
even if what that information may mean is not fully understood?
    Answer. Your question is an important one. As you point out, in
some cases, the technology for genetic testing is out in front of the
evidence for the validity of a genetic test, that is, whether the test
accurately detects the presence of, or predicts the risk for, a
particular health condition. The best approach to genetic testing for
tests that predict the risk of a complex disease such as cancer or
Alzheimer disease is to consult with a genetics professional (e.g., a
genetic counselor, a physician who is board-certified in medical
genetics, or a nurse with specialized genetics training) before and
after testing. Before testing, a genetics professional can explain the
benefits, risks, and limitations of genetic testing. After testing, a
genetics professional can interpret the test results in the context of
a person's medical history, family history, the type of genetic test
(e.g., predictive vs. diagnostic), and the level of evidence for the
test's validity. Professional practice guidelines are also an important
resource to assess the validity of genetic tests.
    The NIH Genetic Testing Registry (http://www.ncbi.nlm.nih.gov/gtr/
), which provides detailed information about tests for more than 4,000
genetic conditions, links to practice guidelines that have been
developed for certain diseases and disorders. For example, tests for
Alzheimer disease link to practice guidelines from the American College
of Medical Genetics, the Agency for Healthcare Research and Quality,
and the European Federation of the Neurological Societies (see http://
www.ncbi.nlm.nih.gov/gtr/conditions/C0002395/). A list of practice
guidelines is available at https://www.ncbi.nlm.nih.gov/medgen/docs/
guideline/. NIH is committed to supporting research that establishes
the genetic contribution to health and disease and providing resources
that help patients and consumers make informed decisions about genetic
testing.
    Question. The National Plan to Address Alzheimer's laid out a
series of actions that must be implemented in order to reach the
overarching goals. For example, NIH has laid out short, medium and
long-term research milestones. In your opinion, are we on schedule to
meet those milestones? Are your current and projected resources
adequate to meet those goals?
    Answer. NIH has been successful in meeting the initial milestones
established in the National Plan, and is well positioned to continue
meeting milestones in the immediate future.
    For example, the National Plan calls for the identification of
research priorities and milestones. NIH has taken the following steps:
  --Conducted the first Alzheimer's Disease Research Summit in May
        2012. The Summit was attended by an international group of some
        500 researchers, clinicians and members of the broader
        Alzheimer's community who worked together to identify research
        priorities and strategies needed to accelerate the development
        of successful therapies. A follow-up Summit is planned for
        2015.
  --Collected feedback on research needs and priorities through a 2012
        Request for Information.
  --Held the Alzheimer's Disease-Related Dementias: Research Challenges
        and Opportunities conference in May 2013 by NINDS, in
        collaboration with NIA and with support from several
        foundations (http://www.ninds.nih.gov/ADRD2013). This
        conference included an international group of experts that
        developed prioritized research recommendations to address AD-
        related dementias including frontotemporal degeneration, Lewy
        body disease, vascular and mixed dementias, as well as clinical
        diagnosis and health disparities in AD-related dementias.
  --Regularly updated the Plan to reflect evolving scientific
        opportunities and needs.
    Elsewhere, the Plan calls for the expansion of research aimed at
preventing and treating the disease. NIH activities in this area
include:
Strategy: Expand research to identify the molecular and cellular
        mechanisms underlying Alzheimer's disease, and translate this
        information into potential targets for intervention.
    Under several FOAs issued in response to the 2012 Summit, NIA has
recently funded several major projects responsive to this strategy:
  --Pathway Discovery, Validation, and Compound Identification for
        Alzheimer's Disease, a study to discover, characterize and
        validate complex molecular networks and candidate genes that
        influence susceptibility to cognitive decline and Alzheimer's
        disease.
  --Integrative Biology Approach to Complexity of Alzheimer's Disease,
        through which investigators will apply innovative analytical
        methods to large-scale molecular, cellular and clinical data
        from Alzheimer's patients to construct biological network
        models and gain new insights into the complex mechanisms of the
        disease. Several cellular and animal models will be used to
        validate the actions of individual genes, as well as entire
        molecular networks predicted to drive the disease.
  --A Systems Approach to Targeting Innate Immunity in Alzheimer's,
        which will use a systems biology approach to integrate genomic,
        gene expression, and pathological data from Alzheimer's
        patients and Alzheimer's mouse models and analyze them in novel
        ways with the goal of identifying and characterizing
        therapeutic targets within the innate immune system. The study
        builds on the genetic and pathological evidence that the innate
        immune system, which provides immediate defense against
        infection, and brain inflammation have a significant role in
        Alzheimer's disease.
Strategy: Expand genetic epidemiologic research to identify risk and
        protective factors for Alzheimer's disease.
    NIA is accelerating the search for genes involved in late onset
Alzheimer's disease (AD) through the AD Genetics Initiative. NIA is
stepping up the collection of a large bank of genetic material, cell
lines, and data from families with multiple members with late-onset AD
at the http://www.ncrad.org/. A case-control series also is being
developed. Qualified scientists will use the bank to search for the
remaining risk factor genes that contribute to late-onset AD, the most
common form of the disease. Scientists will share genetic data
developed from their research on an NIA-approved Web site, usually the
NIA Genetics of Alzheimer's Disease Data Storage Site. Discovery of
risk factor genes will help illuminate the underlying disease processes
of AD, open up novel areas of research, and identify new targets for
drug therapy.
    For a complete update on activities related to the National Plan,
please see http://aspe.hhs.gov/daltcp/napa/NatlPlan2014.shtml
    Consistent with the priorities established at the Alzheimer's
Summit and 2013 ADRD Workshop, NIH will strategically use appropriated
funding to support these priorities. We are currently working
diligently to plan new initiatives for fiscal year 2015 that will
enable us to support additional high priority and high quality
Alzheimer's-related research projects.
    Question. What are the specific breakthroughs in science and
technology that you are targeting to put our understanding of the brain
on the path towards dramatic breakthroughs for diseases like
Alzheimer's, Parkinson's? What are the specific deliverables and
milestones that will get us to this point? Will the Brain Research
through Advancing Innovative Neurotechnologies (BRAIN) Initiative
achieve this or will more need to be done? What is the optimum
investment from both the public and private sector that could be made
in brain research in order to achieve specific deliverables?
    Answer. Many of the symptoms of brain diseases like Alzheimer's,
Parkinson's, autism, and epilepsy, are due to disruption of the complex
neuronal circuits that produce human behavior. To find better
treatments for these diseases, we first need to gain a deeper
understanding into how normal circuits operate and how the changes
wrought by these diseases impair the function of those circuits.
    Currently, we have the technology and computational sophistication
to record and analyze the activity of pairs or small networks of
neurons; however, brain research on neuronal circuits has been limited
because of the difficulty of monitoring activity in many cells at once.
Through the BRAIN initiative, researchers will build on emerging
insights from multiple disciplines to develop, disseminate, and apply
new tools and technologies that will allow scientists to generate a
dynamic, real time picture of entire functioning brain circuits.
Investments in tool development for neuroscience research will empower
investigators beyond those receiving direct funds through the BRAIN
initiative, because a more complete understanding of how brain circuits
function is the necessary foundation for developing new breakthroughs
in how we treat brain disorders like Alzheimer's and Parkinson.
    To develop the BRAIN Initiative's scientific plan, NIH established
a group of 15 highly qualified external scientific advisors, with
additional input from 4 ex officio members from NIH, the National
Science Foundation (NSF), the Defense Advanced Research Projects Agency
(DARPA), and FDA. In September of 2014, this working group of the
Advisory Committee to the NIH Director released an interim report
identifying high priority research areas that are the critical first
steps in supporting the mission of the BRAIN Initiative. Using the
recommendations contained in this report as a guide, NIH released six
funding opportunity announcements that represent the initial steps
towards creating a new arsenal of tools and technologies for
revolutionizing our understanding of the complex interactions within
neuronal circuits. The Working Group's final report, to be released in
June 2014, will contain a multi-year scientific plan, including
recommendations for timelines, milestones, and cost estimates for the
overall initiative.
    In the launch of the BRAIN Initiative, the President recognized
that the next generation of neuroscience breakthroughs will emerge not
only from collaboration across disciplines, but collaboration across
sectors. For this reason, he called for an ``all hands on deck effort''
and has asked the nation to leverage the vast expertise residing within
both the public and private sectors.
    Question. What innovations in computing will be required to advance
brain science? How will we ``mine'' the enormous data that comes from
brain-related simulations to drive discovery, especially in our
understanding of diseases like Parkinson's and Alzheimer's? Are you
currently collaborating with the National Science Foundation on this
initiative? What other agencies are necessary to collaborate with
because of their expertise and strength in high performance computing
in order to achieve the benefits of advanced brain-related simulations?
    Answer. The BRAIN Initiative, and neuroscience in general, present
enormous challenges for computing. The most obvious challenge is the
sheer quantity of data from millions of cells with thousands of
interconnections operating on timescales of thousandths of a second.
But that is just the beginning. Integrating the qualitatively multi-
dimensional data on structure, activity, genes, and other aspects of
nerve cells adds to the complexity, as does the plasticity of the brain
as it continuously adapts. Further, the methods for generating data are
not yet up to computational intensive tasks such as analyzing the
intricacies of brain anatomy. Finally, turning data into understanding
is perhaps the biggest challenge. Unlike the Human Genome Project, for
which the fundamental rules of the genetic code were known at the
start, we have only the faintest glimmers of how information is coded
in the structure and activity of brain circuits.
    Fortunately, there is a long and successful history of applying
computational approaches in neuroscience, from the early days when
scientists determined how nerve cells generate electrical currents and
how signals flow within and between cells, to the more recent advances
in brain imaging, genetics, and protein structure determination, among
many other aspects of modern neuroscience that rely on computational
methods. For this reason, NIH has long supported research at the
interface of computation and neuroscience. One example is a
collaborative program with the NSF begun more than 10 years ago to
encourage interdisciplinary research in computational neuroscience.
Meeting computational challenges has also been a major theme in the
BRAIN Initiative since its inception, including a scientific meeting
last year focused on that topic, and the Initiative is collaborating
closely with the European Union Human Brain Project, whose goal is to
pull together existing knowledge about the human brain via a
supercomputer-based simulation. The broader NIH Big Data to Knowledge
program and the recent appointment of the NIH's first Associate
Director for Data Science will also help meet these challenges.
    Confronting the challenges of brain science is likely to spur
innovations in computer science that have benefits beyond neuroscience,
or even science in general. And there may be a virtuous circle--
learning how the three pound, energy efficient, human brain, which is
composed of cells that act thousands of times more slowly than
electronic circuits, outperforms room size, energy intensive,
electronic supercomputers on some tasks may inspire scientists to
improve the design and programming of tomorrow's computers.
    Question. Seven years ago when the Senate passed the America
COMPETES Act, we committed to steadily increasing basic Federal
research funding over the next 7 years. Today those investments are
paying off at facilities like the High Flux Isotope Reactor (HFIR) at
Oak Ridge National Laboratory.
    Scientists at HFIR have access to some of the most advanced neutron
imaging in the world, which could lead to breakthroughs in brain
related diseases, including Alzheimer's. Recent studies with neutrons
at HFIR have revealed the earliest structural formation of Huntington's
disease, and that research is moving forward to study protein
malformation responsible for Alzheimer's and Parkinson's diseases.
    The problem is that HFIR is the only facility in the world capable
of this type of research, and is primarily dependent on funding from
the Department of Energy. If we want to make substantial breakthroughs
in Alzheimer's, and related diseases, we need to continue to invest in
basic research facilities that can provide scientists with cutting edge
technology, like those found in our national laboratory system.
    Is NIH funding neutron scattering research related to Alzheimer's,
and what additional resources are needed to ensure that researchers
have access to these types of advanced research facilities?
    Answer. NIH is not currently funding neutron scattering research
related to Alzheimer's disease, although we have supported such
research in the past. For example, NIH-supported researchers have used
neutron scattering to determine beta-amyloid's structure and function.
    NIH frequently collaborates with other Federal agencies on
programs, projects, and initiatives related to neuroscience and
Alzheimer's and related dementias. For example, the National
Alzheimer's Project Act Advisory Council includes members from NIH and
other HHS agencies as well as participation from the Department of
Defense, the National Science Foundation, and the Department of
Veterans Affairs. NIA, NINDS, and several other NIH Institutes
participate in the Interagency Working Group on Neuroscience, which was
created to foster collaboration across agencies and to coordinate
Federal investments in neuroscience research. Other members of this
group include the Departments of Agriculture, Defense, Education,
Energy, Health and Human Services, Homeland Security, Justice, and
Veterans Affairs, as well as the CIA, Environmental Protection Agency,
NASA, the National Science Foundation, and the Office of the Director
of National Intelligence. NIH program staff also lend their expertise
to committees and working groups on Alzheimer's and other dementias at
the Department of Defense and the Department of Veterans Affairs.
    Trans-agency coordination efforts will be facilitated by the recent
launch of the International Alzheimer's Disease Research Portfolio
(IADRP), a new, publicly available database to capture the full
spectrum of current Alzheimer's disease research investments and
resources, both in the U.S. and internationally. Developed by NIA in
collaboration with the Alzheimer's Association, the IADRP will enable
public and private funders of Alzheimer's research to coordinate
research planning, leverage resources, avoid duplication of funding
efforts and identify new opportunities in promising areas of growth.
Along with NIA, over 20 NIH Institutes and Centers and a number of
other Federal and non-Federal agencies contribute to the database.
Research organizations from the UK, Canada, and Australia have also
joined the collaboration.
    We anticipate that further collaboration with other Federal
agencies, including those with advanced research facilities such as
those supported by the Department of Energy and the National Science
Foundation, will be a natural outcome of these activities, and we look
forward to continuing to work with these groups to facilitate
additional efforts in Alzheimer's and related dementias.

                         ADDITIONAL STATEMENTS

    The following statements were received subsequent to the
hearing for inclusion in the record.
    [The statements follow:]
        Prepared Statement of Alzheimer's Foundation of America
    On behalf of the Alzheimer's Foundation of America (AFA), a
national nonprofit organization that unites more than 1,600 member
organizations with the goal of providing optimal care and services to
individuals confronting dementia, and to their caregivers and families,
I want to express my gratitude to the Senate Appropriations Committee
for recognizing the growing crisis surrounding Alzheimer's disease and
taking concrete steps to mitigate the impact of this devastating brain
disorder.
    Specifically, we thank the Committee for instructing the National
Institutes of Health (NIH) to increase funding for Alzheimer's disease
research by at least $80 million in the fiscal year 2014 budget. In
addition, this hearing will allow for greater awareness of the negative
impact Alzheimer's disease has on American families and our society.
                      costs of alzheimer's disease
    As the incidences of Alzheimer's disease grow, costs are
skyrocketing. A recent RAND study of adults aged 70 and older found
that the total economic cost of dementia in 2010 was estimated to be
$109 billion for direct care--higher than heart disease and cancer; and
$159 billion to $215 billion when cost of informal care is included.\1\
The per-person cost of dementia was $56,290 or $41,689. Medicare paid
about $11 billion of dementia-related costs. In 2012, the direct costs
of caring for people with Alzheimer's disease or other dementias to
American society will total an estimated $200 billion, including $140
billion in costs to Medicare and Medicaid.\2\ These costs will soar to
a projected $1.1 trillion (in today's dollars) by 2050.\3\ This
dramatic rise includes a 500-percent increase in combined Medicare and
Medicaid spending.
---------------------------------------------------------------------------
    \1\ Monetary Costs of Dementia in the US, www.rand.org/pubs/
external_publications/EP50247.html.
    \2\ Ibid.
    \3\ Ibid.
---------------------------------------------------------------------------
    Complicating this condition, people with Alzheimer's disease tend
to have multiple co-existing medical conditions, such as coronary
artery disease, diabetes, congestive heart failure, and chronic
obstructive pulmonary disease. Thus, they tend to have higher rates of
healthcare use than others without the disease. For example, hospital
stays are more frequent among people with Alzheimer's disease than
among those without this brain disorder.\4\ In addition, avoidable
hospitalizations are more common among Medicare beneficiaries with
Alzheimer's disease than for diabetes (short-term and long-term
complications of diabetes) and hypertension, COPD or asthma, and heart
failure.\5\ These results suggest that Alzheimer's disease creates
additional challenges in managing certain comorbidities, resulting in
higher costs.
---------------------------------------------------------------------------
    \4\ Zhanlian Feng, PhD, et.al., Hospital and Emergency Department
Use by People with Alzheimer's Disease and Related Disorders: Final
Report (August 2013) (http://aspe.hhs.gov/daltcp/reports/2013/
ADRDhed.shtml#execsum).
    \5\ Ibid.
---------------------------------------------------------------------------
    Facing this crisis, strides are being made. Congress and the
Administration passed the National Alzheimer's Project Act (NAPA) \6\
that resulted in the historic ``National Plan to Address Alzheimer's
Disease'' (national Alzheimer's plan), which calls for a cure or
effective treatment by 2025. To reinforce commitment to this goal,
Congress appropriated at least an additional $80 million investment for
Alzheimer's disease research at NIH in the fiscal year 2014 budget,
along with funding for the BRAIN Initiative, which will help
researchers unlock the mysteries of the brain. In addition,
international efforts to confront Alzheimer's disease are developing,
as leaders at the recent G-8 Summit announced that G-8 countries have
committed to identifying a cure or a disease modifying therapy by 2025
and to increase world-wide funding for dementia research.\7\
---------------------------------------------------------------------------
    \6\ National Alzheimer's Project Act (Public Law 111-375), passed
unanimously by Congress in December 2010 and signed into law by
President Barack Obama in January 2011.
    \7\ See, G-8 Dementia Summit Declaration (December 2013)
(www.gov.uk/government/publications/g8-dementia-summit-agreements/g8-
dementia-summit-declaration).
---------------------------------------------------------------------------
                          afa recommendations
``Double Down'' on Alzheimer's disease research funding at the National
        Institutes of Health (NIH).
    AFA is asking Congress for $500 million in additional resources,
for a total over $1 billion, for Alzheimer's disease research and
enhanced investments for caregiver supports in the fiscal year 2015
budget.
    Efforts are already underway in the Senate to ramp up funding for
Alzheimer's disease research and caregiver services. Senators Collins
and Klobuchar have introduced S. Res. 303, a resolution calling on the
U.S. Senate to make fighting Alzheimer's disease an urgent national
priority and to increase funding to $2 billion by fiscal year 2019. We
urge all Senators to support this bipartisan effort and pass S. Res.
303.
Adopt a direct home care coordination model that targets people with
        dementia.
    Several dementia care coordination demonstration projects are
currently being conducted by the Centers for Medicare and Medicaid
Innovation (CMMI).\8\ We urge Congress to instruct the Centers for
Medicare and Medicaid Services (CMS) to build upon these efforts and
expand these successful care coordination delivery models nationwide.
---------------------------------------------------------------------------
    \8\ See, http://innovation.cms.gov/index.html.
---------------------------------------------------------------------------
Develop a new Medicare Alzheimer's disease benefit that extends home
        care and case management services to individuals with
        Alzheimer's disease.
    Congress should instruct the CMS to allow greater case management
for beneficiaries diagnosed with Alzheimer's disease who have
difficulty with one or more activities of daily living (ADLs), as well
as access to home- and community-based services, despite not falling
into the current statutory definition of ``skilled need'' and,
therefore, not ``homebound'' for the purpose of qualifying for the
Medicare home health benefit.
Establish a Medicare palliative care benefit for people with chronic
        conditions, including Alzheimer's disease and related
        dementias.
    We urge Congress to reform the palliative care benefit under
Medicare to make it a viable end-of-life option for individuals with
dementia.
Support expansion and funding Older Americans' Act (OAA) programs.
    Congress needs to pass OAA Reauthorization legislation that has
been introduced in both the Senate and House (S. 3562, H.R. 3850).
Absent these vital OAA supports, the dementia population and their
families would face increased hardships, greater challenges and higher
costs.
Pass the HOPE Act.
    S. 709, the Health Outcomes, Planning and Education (HOPE) for
Alzheimer's Act, provides for Medicare reimbursement to help increase
the detection and diagnosis of Alzheimer's disease and other dementias.
Specifically, the HOPE Act would establish a new benefit for Medicare
beneficiaries for diagnostic and care planning services for people with
Alzheimer's diseases and related dementias. It would also ensure that a
diagnosis of Alzheimer's disease or dementia is included in the
individual's medical record.
    AFA calls on Congress to pass the HOPE Act (S. 709, and its
companion in the House H.R. 1507).
Adopt the Veterans' Administration REACH II program to support family
        caregivers of individuals with Alzheimer's disease.
    Resources for Enhancing Alzheimer's Caregiver Health II (REACH II)
is a multicomponent psychosocial and behavioral training intervention
for caregivers of individuals with Alzheimer's disease or a related
dementia. The intervention is designed to reduce caregiver burden and
depression, improve caregivers' ability to provide self-care, provide
caregivers with social support, and help caregivers learn how to manage
difficult behaviors in care recipients.\9\
---------------------------------------------------------------------------
    \9\ Resources for Enhancing Alzheimer's Caregiver Health II,
National Registry of Evidence-based Programs and Practices, (http://
nrepp.samhsa.gov/Index.aspx).
---------------------------------------------------------------------------
    AFA calls on Congress to encourage nationwide adoption of the REACH
II program for all Medicare/Medicaid beneficiaries who have dementia
and one ADL limitation.
Establish an adult day program benefit under Medicare and mandate adult
        day program as a State Medicaid benefit.
    Adult day services provide socialization and stimulation to people
with Alzheimer's disease and provide respite to family caregivers. They
also provide family caregivers an avenue to maintain a worker/caregiver
balance, which may enable them to stay economically productive in the
workforce while serving as primary caregivers. AFA recommends Congress
make adult day services a benefit under both the Medicare and Medicaid
programs. Representative Sanchez has introduced legislation in the
House (H.R. 3334), that would establish an adult day care option under
Medicare.
Pass the ABLE Act.
    Introduced by Senator Casey S. 313, the Achieving a Better Life
Experience (ABLE) Act will help families and individuals defray costs
associated with caring for a person with Alzheimer's disease or other
dementias. Under the legislation, family caregivers will be able to tap
into new ABLE accounts, modeled after the popular 529 college education
saving program, that will allow contributions to grow tax free and
would be easy and inexpensive to create. We urge Congress to pass S.
313 and its companion bill in the House (H.R. 647).
Provide interventions for family caregivers of individuals with
        Alzheimer's disease and related dementia to delay nursing home
        placement.
    AFA recommends Congress to instruct CMS to develop and implement
caregiver intervention strategies for family caregivers of individuals
with Alzheimer's disease. Greater access to effective programs of
education, counseling and support could yield considerable benefits for
caregivers and cost savings to Federal health programs through deferred
nursing home placements.
Increase geriatric and dementia care training to direct care workers
        who participate in Federal health programs.
    AFA urges Congress to require direct care workers in Federal health
programs to meet specific training standards in geriatrics and dementia
to ensure that individuals with Alzheimer's disease and their family
caregivers have access to high quality long term services and supports
(LTSS) that can specifically address behavior modifications that result
from dementia.
Establish tax credits for people with Alzheimer's disease and their
        family caregivers.
    Congress, through the tax code, should provide greater incentives
for family members who help shoulder the enormous and typically lengthy
responsibilities of providing care for a loved one with Alzheimer's
disease.
Develop transitional housing for individuals with Alzheimer's disease
        and their family caregivers based on the Housing Opportunities
        for People with AIDS (HOPWA) model.
    AFA recommends Congress address the transitional housing needs of
individuals with Alzheimer's disease and their families. The Department
of Housing and Urban Development (HUD) has developed a successful
transition housing model, Housing Opportunities for People with AIDS
(HOPWA), for low-income Americans living with HIV/AIDS and their
families. AFA urges adopting the HOPWA model for low-income persons
with Alzheimer's disease or related dementias.
                               conclusion
    The status quo is inadequate to meet the growing needs anticipated
by the ``silver tsunami'' as our population ages and incidence of
people with Alzheimer's disease and their family caregiver multiplies.
AFA's recommendations will help advance promising research while
strengthening the safety net for individuals with LTSS needs, as well
as support family members and other unpaid caregivers, whose
participation in providing LTSS will continue to be essential. In
addition, new delivery models that increase care management and care
coordination will lower overall healthcare costs while allowing for
more healthy outcomes for both the increasing number of people with
Alzheimer's disease and their family caregivers.
    AFA looks forward to working with Congress, the Administration and
Alzheimer's disease stakeholders to ensure that a meaningful increase
in Alzheimer's disease funding becomes a reality in fiscal year 2015
and moves us closer to attaining the ambitious, yet essential, care-
and research-related goals of the national Alzheimer's plan.




    This statement was submitted by the Honorable Charles J. Fuschillo,
Jr., Chief Executive Officer, Alzheimer's Foundation of America.
                                 ______

  Prepared Statement of United Domestic Workers of America, American
  Federation of State, County and Municipal Employees (AFSCME), Local
                                  3930
    The United Domestic Workers of America (UDW), AFSCME Local 3930, is
a union for homecare workers, by homecare workers. We look after loved
ones in our families, or we care for community members who need our
assistance through California's In-Home Supportive Services (IHSS)
program. Many of us left paid, full-time jobs to do this work, and we
frequently work more hours than we are paid for. And while our work is
incredibly rewarding, it is also extremely hard. This is why we have
come together to offer each other a community of support. Through our
union we connect with each other, advocate for our clients, and we also
advocate for each other.
    Many UDW members are experts on Alzheimer's. They see how the
disease progresses. They know how it steals memories. They know how it
can change proud and strong people by taking away their ability to
perform basic activities of daily life. UDW members are authorities on
what those changes mean to individuals, caregivers and families. They
see what Alzheimer's and dementia mean economically, emotionally,
physically and socially. This disease may change a person but it can
never take away a person's humanity because UDW homecare providers are
heroes. They help people keep their dignity. They help people remain in
their own home even as the disease takes its toll.
    Sylvia Peralta is 62. For the last decade she has been taking care
of her parents, who both have dementia. Her father and mother were born
in the United States. They worked hand in hand in fields and canneries
to build a better life for their children. When her father's medical
condition deteriorated he could no longer safely remain at home. For
Sylvia and her mother, the toughest times are when her mother cries
because she does not understand why her husband of 64 years has left.
It is Sylvia's compassionate and repeated reminders that make it
possible for her mother to get through those hours.
    Carolyn Haines's 18-month-old daughter tragically fell in a
swimming pool and sustained traumatic injuries. She is now middle-aged
and unable to speak, feed herself or hold things in her hands. But
because of Carolyn's care for her at home, she is very social, attempts
to speak and lights up a room with her laughter. When Carolyn's husband
started to say inappropriate things, Carolyn knew something was
different. It was Alzheimer's. In addition to taking care of her
daughter, Carolyn took care of her husband as he went through the
progressive decline from the disease for 11 years. She wasn't prepared
for all the changes, particularly when he became combative. A month
before he died, he said ``I love you.'' It was the first clear thing he
said to her in 6 months. She clung to that through his last days.
    The stories of Sylvia and Carolyn and tens of thousands of UDW
members are proof of the true value of homecare providers.
Unfortunately, Federal and State spending on homecare can tell a
different story.
    Research to prevent and treat Alzheimer's disease is important for
a better future, but in the absence of a cure, it would be wrong for
Federal spending decisions to overlook the need to respect and value
homecare providers. Families dealing with Alzheimer's today ask, ``Who
will care for my loved one today and tomorrow and the next day?'' For
too many families the answers boil down to unacceptable choices.
    Federal dollars must fuel a caring revolution to help homecare
providers and those whose independence depends on in-home services and
supports. Targeting Federal funds to encourage States to increase
spending for homecare providers is the right thing to do and makes
economic sense. Homecare work cannot be outsourced and this workforce
spends its income in their communities. To meet the growing demand for
services and to stabilize this workforce, we need our State and
national spending policies to provide increased dollars to sustain
quality homecare through better homecare jobs.
    Sylvia, Carolyn and the tens of thousands of homecare providers who
get up early and go to bed late caring for others are courageous.
Courage does not mean being fearless. They have more than their share
of fears and heartache. They have courage because they are brave to do
what they do every day and keep on doing it.
    We call upon Congress to have the courage to do right by these
workers and those who depend on their care. We urge Congress to
increase Federal spending for homecare and to make sure States increase
their funding for homecare providers like Sylvia and Carolyn.
                                 ______

                Prepared Statement of USAgainstAlzheimer
    Chairman Harkin, Ranking Member Moran, Chairwoman Mikulski and
members of the committee. I applaud you for convening this hearing to
focus on the urgent health and financial crisis that is Alzheimer's
disease. Given the magnitude of this issue, it is quite fitting that
Alzheimer's is the topic of the committee's first hearing of the fiscal
year 2015 appropriations cycle. It is also apt that you have chosen to
focus on the economic impact of Alzheimer's on American families and
the economy as a whole.
    In Washington, the term crisis is often overused to the point where
it becomes an empty modifier devoid of its true meaning. However, the
term crisis is quite accurate when it comes to Alzheimer's,
particularly considering the looming health and financial burdens if
the current trajectory remains unchanged.
    Thankfully, our Government has stepped up in a significant way to
recognize the enormity of this threat. A little more than 3 years ago,
Congress passed and the President signed into law legislation
establishing the National Plan to Address Alzheimer's Disease. Two
years ago, the first iteration of that plan was released, setting as
goal one the prevention and effective treatment of Alzheimer's disease
by 2025. 2025. Think about that. It may seem far off but it is just a
little more than a decade away or less than two terms in the Senate. We
all know how quickly this date will be upon us and that we must,
therefore, do everything in our power to maximize our chances of
achieving this goal.
    We are making progress, thanks in large part to the work of this
committee. Just last month, Congress increased the budget for the
National Institute on Aging (NIA) in a way that can provide for about
$100 million in increased Alzheimer's research in fiscal year 2014.
According to the National Institutes of Health (NIH), about $562
million will be spent on Alzheimer's. While this is a laudable increase
during a time of flat or declining funding, I fear it remains
insufficient to satisfy the task at hand.
    Leading Alzheimer's scientists, as well as the Advisory Council on
Alzheimer's Research, Care and Services, have estimated that an annual
U.S. Government commitment of $2 billion to Alzheimer's research is
needed if we are serious about achieving the 2025 goal. The current
level of appropriated funding, even with some recent increases, is a
little more than one-quarter of the amount recommended by leading
experts.
    At the recent meeting of the Advisory Council, leading Government
officials noted that the current level of funding is simply inadequate
to achieve the 2025 goal given the immense scientific challenges--and
the opportunities--before us today. While we recognize the fiscal
challenges impacting the Nation and the need for substantive and
lasting debt, deficit, entitlement and tax reform, the reality is that
we simply do not have a choice as to whether or not we will pay for
Alzheimer's. We are already paying, quite dearly I might add, in the
form of nearly $150 billion in Medicare and Medicaid costs to care for
these patients. And we will pay even more money--both public and
private--over the coming years and decades absent breakthroughs in
research that lead to the development of therapies able to slow,
modify, stop and ultimately reverse the effects of Alzheimer's.
    I urge this committee to do all you can to continue building on
these recent gains and to capitalize on the possibilities by committing
to double--to about $1 billion--the amount of NIH funds available for
high-quality and meritorious Alzheimer's research. Just as you did in
the past year, you can do so without breaking longstanding policy and
directing the dollars to a specific disease. Rather, just as NIH funds
institutes focused on cancer, diabetes, heart disease and HIV/AIDS, you
can allocate the funding to the NIA so it can be used assuming enough
meritorious applications are submitted.
    I also urge you to look beyond the 1 year funding cycles of the
Federal budget and appropriations process to envision this as part of
an effort to achieve the $2 billion target over the coming 4 to 5
years. Such a multi-year commitment--similar to what Congress bravely
did a decade ago to double the overall NIH budget--will provide the
level of resources deemed necessary to achieve our national goal. This
action would send an important signal to non-government entities--
academia, industry, venture capital, and philanthropists--that the U.S.
Government is firmly committed to Alzheimer's research and that they
should make similar financial commitments. And it would also send a
message to global governments--some of which are already calling for a
similar commitment--that the U.S. is ready and willing to lead this
effort, just as we have led on so many other critical health issues
over the decades.
    Preventing and effectively treating Alzheimer's disease by 2025 is
not an easy goal. In fact, it is a daunting goal, and the outcome is
far from guaranteed. The U.S. has a long history of setting and
achieving ambitious goals when we commit our minds, our hearts and our
resources to the task. In the fall of 1962, the idea of landing a man
on the moon in less than a decade was fantastical to many, yet we were
able to achieve the goal with time to spare. Stopping Alzheimer's
within 11 years can seem just as daunting given the state of the
science and the spate of recent setbacks. However, I remain convinced
that we can--and we will--achieve this goal if our resolve remains
steadfast and if the appropriate level of resources is allocated.

    This statement was submitted by George Vradenburg, Chairman.
                                 ______

  2012-2013 Alzheimer's Disease Progress Report: Seeking the Earliest
                             Interventions
    The report ``2012-2013 Alzheimer's Disease Progress Report: Seeking
the Earliest Interventions, Preview Copy, December 2013'' from the
National Institute on Aging, National Institutes of Health is available
at the following link: www.nia.nih.gov/
alzheimers/publication/2012-2013-alzheimers-disease-progress-report/.

                         CONCLUSION OF HEARING

    Senator Harkin. Thank you very much.
    Housekeeping. The record will remain open until March 5 for
other statements and comments from other Senators.
    Thank you all very much. Safe travels home, everybody. Safe
travels home.
    [Whereupon, at 4:02 p.m., Wednesday, February 26, the
hearing was concluded, and the subcommittee was recessed, to
reconvene subject to the call of the Chair.]

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