[House Hearing, 115 Congress]
[From the U.S. Government Publishing Office]
A GLOBAL UPDATE ON ALZHEIMER'S DISEASE
SUBCOMMITTEE ON AFRICA, GLOBAL HEALTH,
GLOBAL HUMAN RIGHTS, AND
COMMITTEE ON FOREIGN AFFAIRS
HOUSE OF REPRESENTATIVES
ONE HUNDRED FIFTEENTH CONGRESS
NOVEMBER 29, 2017
Serial No. 115-89
Printed for the use of the Committee on Foreign Affairs
Available via the World Wide Web: http://www.foreignaffairs.house.gov/
U.S. GOVERNMENT PUBLISHING OFFICE
27-661 PDF WASHINGTON : 2018
For sale by the Superintendent of Documents, U.S. Government Publishing Office,
http://bookstore.gpo.gov. For more information, contact the GPO Customer Contact Center,
U.S. Government Publishing Office. Phone 202-512-1800, or 866-512-1800 (toll-free).
E-mail, [email protected]
COMMITTEE ON FOREIGN AFFAIRS
EDWARD R. ROYCE, California, Chairman
CHRISTOPHER H. SMITH, New Jersey ELIOT L. ENGEL, New York
ILEANA ROS-LEHTINEN, Florida BRAD SHERMAN, California
DANA ROHRABACHER, California GREGORY W. MEEKS, New York
STEVE CHABOT, Ohio ALBIO SIRES, New Jersey
JOE WILSON, South Carolina GERALD E. CONNOLLY, Virginia
MICHAEL T. McCAUL, Texas THEODORE E. DEUTCH, Florida
TED POE, Texas KAREN BASS, California
DARRELL E. ISSA, California WILLIAM R. KEATING, Massachusetts
TOM MARINO, Pennsylvania DAVID N. CICILLINE, Rhode Island
MO BROOKS, Alabama AMI BERA, California
PAUL COOK, California LOIS FRANKEL, Florida
SCOTT PERRY, Pennsylvania TULSI GABBARD, Hawaii
RON DeSANTIS, Florida JOAQUIN CASTRO, Texas
MARK MEADOWS, North Carolina ROBIN L. KELLY, Illinois
TED S. YOHO, Florida BRENDAN F. BOYLE, Pennsylvania
ADAM KINZINGER, Illinois DINA TITUS, Nevada
LEE M. ZELDIN, New York NORMA J. TORRES, California
DANIEL M. DONOVAN, Jr., New York BRADLEY SCOTT SCHNEIDER, Illinois
F. JAMES SENSENBRENNER, Jr., THOMAS R. SUOZZI, New York
Wisconsin ADRIANO ESPAILLAT, New York
ANN WAGNER, Missouri TED LIEU, California
BRIAN J. MAST, Florida
FRANCIS ROONEY, Florida
BRIAN K. FITZPATRICK, Pennsylvania
THOMAS A. GARRETT, Jr., Virginia
JOHN R. CURTIS, UtahAs of
12:44 pm 11/29/17 deg.
Amy Porter, Chief of Staff Thomas Sheehy, Staff Director
Jason Steinbaum, Democratic Staff Director
Subcommittee on Africa, Global Health, Global Human Rights, and
CHRISTOPHER H. SMITH, New Jersey, Chairman
MARK MEADOWS, North Carolina KAREN BASS, California
DANIEL M. DONOVAN, Jr., New York AMI BERA, California
F. JAMES SENSENBRENNER, Jr., JOAQUIN CASTRO, Texas
Wisconsin THOMAS R. SUOZZI, New York
THOMAS A. GARRETT, Jr., Virginia
C O N T E N T S
Marie Bernard, M.D., Deputy Director, National Institute on
Aging, National Institutes of Health........................... 6
Roger Glass, M.D., Director, Fogarty International Center,
National Institutes of Health.................................. 8
Mary Mittelman, Dr.P.H., research professor, Alzheimer's Disease
and Related Dementias Family Support Program, New York
Richard Mohs, Ph.D., chief scientific officer, Global Alzheimer's
Platform Foundation............................................ 35
Mr. Michael Splaine, principal, Splaine Consulting............... 41
LETTERS, STATEMENTS, ETC., SUBMITTED FOR THE HEARING
Marie Bernard, M.D., and Roger Glass, M.D.: Prepared statement... 10
Mary Mittelman, Dr.P.H.: Prepared statement...................... 30
Richard Mohs, Ph.D.: Prepared statement.......................... 38
Mr. Michael Splaine: Prepared statement.......................... 44
Hearing notice................................................... 60
Hearing minutes.................................................. 61
Material submitted for the record by the Honorable Christopher H.
Smith, a Representative in Congress from the State of New
Jersey, and chairman, Subcommittee on Africa, Global Health,
Global Human Rights, and International Organizations:
Joint testimony of Alzheimer's Association and Alzheimer's
Impact Movement.............................................. 62
``External Validity of the New York University Caregiver
Intervention: Key Caregiver Outcomes Across Multiple
Demonstration Projects''..................................... 67
``The Minnesota Economic Model of Dementia: Demonstrating
Healthcare Cost Savings with the New York University
Caregiver Support Intervention''............................. 75
``Estimating The Potential CostSavings From The New York
University Caregiver Intervention In Minnesota''............. 83
A GLOBAL UPDATE ON ALZHEIMER'S DISEASE
WEDNESDAY, NOVEMBER 29, 2017
House of Representatives,
Subcommittee on Africa, Global Health,
Global Human Rights, and International Organizations,
Committee on Foreign Affairs,
The subcommittee met, pursuant to notice, at 2:00 p.m., in
room 2172 Rayburn House Office Building, Hon. Christopher H.
Smith (chairman of the subcommittee) presiding.
Mr. Smith. The subcommittee will come to order, and good
afternoon, everybody. I apologize for the delay. We had a
series of votes, and we have one later, too, so I do want to
get right to it.
I want to thank you for being here. Today, as we open
today's hearing, there are an estimated 47 million people in
the world living with Alzheimer's disease and other forms of
dementia--more than the entire population of Spain, according
to a report by the Alzheimer's Disease International.
The number of victims who have Alzheimer's is projected to
double every 20 years. So we are in a race like few other
diseases because it is proliferating so fast throughout the
And according to Dr. Marie Bernard, the deputy director of
the National Institute on Aging, who we will hear from
momentarily, the number is estimated to grow to 115 million by
2050 as populations around the world age.
Although there is early onset but predominantly it is one
of the byproducts of all of us aging and there seems to be a
higher proclivity the older one gets, and it has been estimated
that once somebody reaches 85 the chances of some form of
dementia is about one out of two. So it's a very, very serious
The total estimated global cost of addressing this
condition today is $818 billion, but by as early as next year
it is estimated that this cost will rise to at least $1
trillion--that is per year--and then it will go up from there.
As we all know, Alzheimer's is a cruel disease, robbing its
victims of their memories and their very identities and robbing
their families and friends of the person they know and love.
It is excruciatingly painful for someone to lose themselves
gradually, and I have spoken myself to many individuals,
especially those who are early onset who have young families
and are dealing with the agony that they know it is
There is no cure. There are drugs, five of them so far, and
others that are in the pipeline that treat symptoms but there
is no actual cure. And so it is very tough and it takes a very
heroic person to cope and manage with that.
We also know that the families have to deal with a very
painful ordeal, as well the care givers, the loved ones, the
family and the friends.
In 1999, along with then-Congressman, now Senator Ed
Markey, I co-founded the Congressional Task Force on
Alzheimer's disease, which I still co-chair today with Maxine
Waters, to bring this disease to the forefront of the
congressional agenda to advance support for Federal research
and to increase awareness.
The task force worked in partnership with the Alzheimer's
Association to unanimously pass the National Alzheimer's
Project Act--or PL 111, which established an advisory committee
of private and Federal experts to work with the secretary of
HHS to comprehensively assess and address Alzheimer's research,
institutional services, and home and community-based care with
the goal to identify a cure or disease-modifying therapy for
dementia by 2025.
Today, there are over 170 members of the House and Senate
in the task force.
This year, we worked very hard in a bipartisan way to get
an increase of some $414 million to the Alzheimer's research
funding at NIH.
Under HHS Appropriations Chairman Tom Cole's extraordinary
leadership, the fiscal year 2018 omnibus appropriations bill
was enacted. It was passed in September of this year.
It included a $400 million increase for Alzheimer's disease
research at the National Institutes of Health. This would bring
total funding to $1.8 billion.
Currently funded at $1.4 billion, NIH spending on
Alzheimer's research has almost tripled since fiscal year 2015
when $589 million was allocated for such research.
Shockingly, the majority of people with Alzheimer's or
other forms of dementia have not received a diagnosis so they
are unable to access the care and the treatment of symptoms
that they so desperately need. This is true in the developed
world but it's even truer in the developing world.
Michael Splaine points out in his testimony today that
detection and diagnosis are a stubborn problem everywhere.
Research shows that most people currently living with dementia
have not received a formal diagnosis, he will testify. In high-
income countries, 20 to 50 percent of dementia cases are
recognized and documented in primary care.
This treatment gap, as he calls it, is certainly much
greater in low and middle income countries. Without a
diagnosis, there can't be treatment care or organized support
or the opportunity to volunteer for clinical research.
Of course, even when Alzheimer's or other forms of dementia
are diagnosed, care is too often fragmented, uncoordinated, and
unresponsive to the needs of people living with the condition.
In response, last Congress I introduced the Health Outcomes
Planning Education--or HOPE--for Alzheimer's Act of 2015 to
provide Medicare coverage for care planning session for
patients newly diagnosed with Alzheimer's disease for family
care givers or legal representatives.
In recognition of this great unmet need, the legislation
garnered 310 bipartisan co-sponsors. Ultimately, the Medicare
adopted an amended version of the HOPE Act--actually an
improvement--for final rule for calendar year 2017's positions
Of course, Alzheimer's robs its victims not only of their
memories but also of their awareness, but also their lives. In
the American Journal of Public Health, a research survey of
years of life lost versus the number of deaths between 1995 and
2015, annual deaths due to Alzheimer's complications in the
U.S. alone rose from 20,607 in 1995 to 110,568 in 2015.
During that period, Alzheimer's rose from the 14th leading
cause of death among ailments in this country in 1995 to number
six in 2015.
For the record, this is my fourth hearing I have chaired on
Alzheimer's disease. On June 23rd in 2011, we held a hearing on
the global strategies to combat the devastating health and
economic impacts of Alzheimer's.
On November 21st, we held a hearing on the G8 Dementia
Summit and beyond, and then in 2014 on the actual summit report
from the G8 and now today's hearing, of course.
Today's hearing is intended to examine the existing
potential options for prevention and treatment of this
devastating disease and the harrowing statistics cited earlier
likely will be much worse in developing countries if they had
accurate identification of Alzheimer's and records of victims
and of deaths.
As our hearing testimony will demonstrate, there is hope
for Alzheimer's patients, their families and friends. There is
a surge, particularly for research.
For example, a research team from Columbia University's
Medical Center in 2013 said they had finally traced Alzheimer's
to its early developmental stages of discovery that they
believe could lead to more effective treatments.
In science translational medicine 3 years ago, Australian
researchers explained a noninvasive ultrasound technology that
clears the brain of neurotoxic amyloid plaques--structures that
are responsible for memory loss and a decline in cognitive
function in Alzheimer's patients.
By 2016, scientists at the Institute of Regenerative
Medicine at the University of Zurich said they were amazed to
find that their patients treated with the highest dose of an
antibiotic drug experienced an almost complete clearance of the
amyloid plaques that prevent brain cells from communicating,
leading to reversible memory loss and cognitive decline.
Our witnesses today will tell us more about these and other
advances that, again, the United States is walking point in the
world in this and we have two tremendous witnesses and experts
who are doing their best and their staffs to make sure that we
get there sooner rather than later.
I would also just point out for the record this Congress
I've joined my colleagues in introducing the BOLD Act, which
would establish Centers of Excellence and it is designed to
really take this to the next level--to have congressional
support for this effort in a more robust way.
I have also reintroduced Kevin and Avonte's Law. It passed
last year in the House. It deals with the wandering issue.
We know that when Alzheimer's or autism individuals have
the bracelet, they are found usually within 30 minutes. When
they don't and they go wandering, it can catastrophic if not a
cause of death from drowning and a whole host of other reasons
if they are not rescued from that wandering.
Next week, I will reintroduce the Global Brain Health Act
to increase research on prevention and treatment of autism,
hydrocephalic condition and Alzheimer's and other forms of
This legislation, which I first introduced in 2015, would
encourage the building of treatment capacity for these brain
disorders among care givers in developing countries and support
increased international cooperation in research and
implementation of strategies on prevention and treatment.
I would like to now yield to Dr. Bera for any opening
comments he might have.
Mr. Bera. Thank you, Mr. Chairman, and thank you for having
this hearing. It, obviously, is incredibly important.
Anytime you can say neurotoxic amyloid plaques in Congress
that is a good day, particularly, as a physician.
So I am trained in internal medicine and taking care of
many Alzheimer's patients and, you know, the urgency of
addressing this issue and, you know, looking for ways to
mitigate the disease but also ultimately looking at ways to
reverse and cure disease are, obviously, our ultimate goals.
You know, I think we often focus here domestically on what
we need to do to help address this issue. But, you know, I work
pretty closely with our Alzheimer's Association and I think the
Alzheimer's Association has done a wonderful job elevating the
level of dialogue but also elevating the dialogue on, you know,
why this is a global epidemic.
Often when we think about global health we are thinking
about the communicable diseases that are out there. But there
really is as--you know, there are more developed nations around
We have got to spend more time thinking about the impact of
noncommunicable diseases like Alzheimer's disease.
You know, as we start to think about those public health
approaches, from my public health background, you know, there
is a number of things that, you know, are the low-hanging
fruit--you know, the lifestyle modifications, the things that
you can do to certainly slow down and mitigate disease.
A second step is building the public health infrastructure
in the global community to help both families and patients
manage and navigate that disease and, again, I do think we are
going to see this coming tidal wave as people live longer in
the global community, the lack of infrastructure and the lack
of readiness to, you know, manage this tidal wave of folks
with--with dementia and with Alzheimer's disease and other
noncommunicable diseases, for that matter.
And then, you know, long term this is a global challenge
and I look forward to hearing from the witnesses. You know, we
can quantify the direct costs of Alzheimer's but then also the
indirect costs of Alzheimer's in terms of, you know, both the
patient as well as the impact on families and care givers.
And then, ultimately, you know, part of the reason why I am
such a strong advocate for making investments in the NIH and
making investments in research is the return on that investment
if we are able to find a cure or even better therapies to
mitigate disease and slow down disease is going to be, you
know, pretty significant, because if we don't we will be
spending billions upon billions of dollars on the back end. And
this is not just a U.S. challenge. This is a global challenge.
So, Mr. Chairman, I think this is a incredibly timely topic
and I look forward to hearing from the panelists. So thank you.
I yield back.
Mr. Smith. Thank you, Dr. Bera.
I would like to now yield to Mr. Donovan for any comments
he might have.
Mr. Donovan. Thank you very much, Mr. Chairman. Thank you
for conducting this very important hearing.
Many of the things that this committee does deals with
diseases and things people are suffering from that we don't
suffer from in this country.
When I came to Congress, 2 weeks later at 58 years old I
had my very first baby. Her mother actually describes her as my
very last baby, by the way.
But so all of a sudden, maternal health and infant health,
prenatal care became so important to me because it was personal
to me. And I always say that Yellow Rose Catherine was--she hit
the birth lottery.
She was born on May 19th of 2015 on the same day tens of
thousands of other children were born, except she was born on
Staten Island in New York City and has had every one of her
vaccinations, every one of her well visits, and children born
that same day who didn't hit that birth lottery didn't have the
same advantages she did. So there's a lot of things this
committee has done has been personal to me.
I am also the only son of an Alzheimer's patient. My mother
died the year before I was elected after suffering for 4 years.
I was blessed. I had her until she was 89 years old and her
mother died when she was 9. So I always say I had my mother for
50 more years than she had her own mother.
But I watched this woman become someone I didn't know--a
woman who was always calm who became violent--a woman who would
sit and just stare even when you speak to her because she no
longer could communicate or understand what you're saying.
And I learned a lot about the disease--not as much as my
friend, Dr. Bera, but--about the proteins that grow on people's
brains and how advancements in medicine now are finding ways to
slow that protein growth down, maybe stop it altogether, maybe
at some point actually have medication that could remove the
proteins from people's brains that may cure the disease is our
I know that we gave the National Institute of Health in the
21st Century Cures Act billions of dollars to help the
advancement of some treatments and cures for things like
So I just wanted to tell my personal story just so I could
tell you how much I appreciate you being here and how important
this is in a global health environment, but how personally it
has touched me. So I thank you both for being here today and
thank you, Mr. Chairman.
Mr. Smith. Thank you very much.
At this time, let me introduce our distinguished witnesses
and, again, thank them for their tremendous leadership,
beginning with Dr. Marie Bernard, who serves as deputy director
of the National Institute on Aging at the National Institutes
Dr. Bernard serves as the principal advisor to the NIA
director, working closely with the director in overseeing
approximately $2 billion in aging research conducted and
supported annually by the institute.
Dr. Bernard co-chairs two department Health and Human
Services Healthy People 2020 objectives--older adults and
dementias, including Alzheimer's disease.
We will then hear from Dr. Roger Glass, who I'd point out
is also from New Jersey originally--from Summerville, New
Jersey. He serves as the director of the Fogarty International
Center and associate director for international research at the
National Institutes of Health.
Dr. Glass has maintained field studies in India,
Bangladesh, Brazil, Mexico, China, and elsewhere in the world.
He has received numerous rewards including the prestigious
Charles Shepherd Lifetime Scientific Achievement Award
presented by the Centers for Disease Control and the Charles--
Dr. Charles Merieux Award from the National Foundation for
Infectious Diseases for his work on the rotavirus vaccines in
the developing world.
Two experts and two very much welcomed witnesses to our
STATEMENT OF MARIE BERNARD, M.D., DEPUTY DIRECTOR, NATIONAL
INSTITUTE ON AGING, NATIONAL INSTITUTES OF HEALTH
Dr. Bernard. Well, good afternoon, Chairman Smith,
Representative Bera, Representative Donovan.
I am happy and honored to represent the National Institute
on Aging, one of the 27 institutes and centers at NIH. We, at
the NIA, lead NIH's Alzheimer's disease research and as deputy
director I bring my experience as an academic geriatrician.
I could very much empathize with the points that were made
with regards to the prevalence of this illness and the personal
impact that it had on families.
When I saw patients on a daily basis it was heartbreaking
to see the impact that this had on those patients and,
importantly, on their family members and to recognize that I
didn't have much in my armamentarium that I could bring to the
care of those individuals at that time.
It's encouraging to be at NIH at this point and to see the
blossoming of more and more information that is developed with
global partners that will hopefully get us to the point that we
will have a prevention or cure for this illness.
We have, in fact, over the decades supported a number of
international studies that have led us to a greater
understanding of the illness and I will spend what time is
allocated to me to briefly highlight three of those.
First, we are making significant advances in our
understanding of the course of Alzheimer's disease from our
health and retirement study.
This is a 20-year-old national sampling of older adults in
the United States--people 50 years of age and older who have
followed through to their death--and it has allowed us to see
the natural course of aging as well as the natural course of
the development of Alzheimer's disease.
This study has recently had a new component added to it
that's an international component--the Harmonized Cognitive
Assessment Protocol, or HCAP.
We have the hope that if we can get researchers across the
globe to harmonize the way that they go about cognitive
assessments, we will be able to better understand the course of
the illness and to sort out the genetic, social, and
environmental influences that impact Alzheimer's disease.
We are supporting the deployment of HCAP and HRS, or Health
and Retirement Study, like studies in England, Mexico, China,
and India, as well as a smaller scale study in South Africa.
This will provide us an unprecedented scientific opportunity.
A second important need is for means to make the diagnosis
of Alzheimer's earlier than the current standard, which is when
a person has cognitive and functional problems.
There are many promising new findings, particularly as a
result of something called the Alzheimer's Disease Neuroimaging
Initiative, or ADNI. ADNI is a worldwide collaboration with
organizations in Europe, Japan, Australia, Taiwan, Korea,
China, and Argentina.
ADNI has led to the identification of biomarkers, proteins,
and images of the brain that allow us to measure the onset and
progression of this disease.
A decade ago, the only way that you could definitively say
that someone likely had Alzheimer's disease or had Alzheimer's
disease was by autopsy.
But now we can see in a living brain the deposition of
amyloid plaques and tau tangles in an individual and follow its
course before they have clinical symptoms.
As we make progress with validating this and other
biomarkers, we hope to translate this into useful clinical
Third, NIA-supported investigators are conducting
prevention and treatment trials that are globally--or have a
One such study which has received quite a bit of attention
is the Autosomal Dominant Alzheimer's Disease Trial involving
the world's largest group of early-onset familial Alzheimer's
disease--approximately 300 extended family members in the
country of Columbia who share a rare genetic mutation that
guarantees that by middle age they are going to have
The trial focuses on whether an anti-amyloid drug,
crenezumab, can prevent or delay the onset of cognitive
We are very grateful to this family and all participants in
Alzheimer's disease and related trials. They are true heroes
who have allowed us to learn and continue to learn about this
Finally, I would say that my patients would tell me every
day that they did not want to live--to grow older if they did
not have their cognitive capacity because they did not want to
become a burden to their families.
We, with global partners, are working diligently to develop
answers to their concerns. With the global rise of Alzheimer's
prevalence, the situation is urgent, as you well-articulated,
and we are using every possible approach to diminish the impact
of this disease as rapidly as possible.
Thank you for allowing me to testify, and I look forward to
Mr. Smith. Thank you so very much, Dr. Bernard, for your
testimony and for your insights.
STATEMENT OF ROGER GLASS, M.D., DIRECTOR, FOGARTY INTERNATIONAL
CENTER, NATIONAL INSTITUTES OF HEALTH
Dr. Glass. Thank you, and good afternoon, Chairman Smith,
Acting--Ranking Member Bera, and distinguished member Donovan.
I too had a father with Alzheimer's and I sympathize and
went through the same experience.
I am Roger Glass. I am the director of the Fogarty
International Center at the National Institutes of Health and I
am honored to join my colleague, Dr. Bernard, here in
discussing how we are confronting the global burden of
Diseases like Alzheimer's and like flu and ebola know no
borders. People throughout the world suffer from this disease
and will benefit from treatments and cures.
We need to find the brightest minds everywhere to assist in
this endeavor as well as to identify populations with unique
environmental or genetic risks because the high quality
research that we do doesn't happen only in the United States.
It happens elsewhere.
In order to take advantage of these international
situations, we need the best trained scientists with high
ethical standards, with good data management capabilities, with
laboratories capable of conducting the research that's
Fogarty International Center at NIH facilitates building
these research partnerships leading to capacity, building
capacity for researchers internationally to create the next
generation of scientists who will address the Alzheimer's
These scientists who will address these problems in the
future are just being trained today. As Dr. Bernard mentioned
in her remarks, NIA is supporting the study in Colombia of an
extended family with a genetic mutation for familial
This family is now center stage for much of our research on
Alzheimer's cures and preventions. This partnership began in
the early 1990s when an American investigator, Ken Kosik, then
at Harvard, met a Colombian physician, Dr. Francisco Lopera.
Dr. Lopera, as a young neurologist, had a patient with
Alzheimer's and found that the patient's father and grandfather
had Alzheimer's, and because of his curiosity as a young
physician, not as a researcher, he sought out and ultimately
developed a cohort of 5,000 people with this genetic problem
and it was from this conversation 6 years later of these
American and Colombian investigators that they began a decade-
long collaboration to look and see what they could learn about
the epidemiology and genetics of Alzheimer's.
This investigation has proved incredibly fruitful beyond
our wildest expectations. In the 1990s, these doctors received
a grant from Fogarty to work together.
By 2004 and '07, the National Institute of Aging and
Fogarty were both engaged in supporting this collaborative
And this research involved not only following up on the
cohort but training people in laboratory methods, in building
capacity so that we could actually conduct quality research
under the best ethical standards in the field.
At the same time, it also engendered collaborations between
communities that were invested. These were not patients in
Colombia. These were community participants in research--a big
Preparing for scientists to conduct high-impact research is
critical to the Fogarty agenda and what began as a partnership
between these two scientists--individual scientists is now at
the cutting edge of what's become a $100 million clinical
trial, the first in the world for early prevention of the
progression of Alzheimer's disease.
It is a unique study that couldn't be done anywhere else
and this cohort was really an incredible finding and discover
of Dr. Lopera. He's an essential part of the research team as
is his laboratory in Colombia--in Medellin, Colombia.
Colombia is not unique in this. While the topic of today's
discussion is Alzheimer's disease, the Fogarty Center has also
been involved in many other neurological problems such as
research on cerebral malaria, neuro HIV, hydrocephalus in
Uganda, epilepsy in Zambia, chronic psychotic disorders in
Tanzania, and stroke outcomes in Zimbabwe, just to name a few.
Fogarty supports--takes science where the problems are and
where the opportunities are for the most rapidly accelerating
advances in research. And we also are concerned in developing
true partnerships for research and advancing capacity building.
Like Dr. Lopera, who is a unique investigator in a unique
setting with a unique population of this familial Alzheimer's
disease, it's leading us to, hopefully, more rapid cures.
From this partnership and with NIH support, we are already
advancing discovery research. We are already working in basic
research in Colombia in collaboration with the U.S.
The group in Colombia is now an integral part and a central
part of the U.S. research endeavor on Alzheimer's and the
results of this endeavor both for the U.S. population and for
the population in Colombia and around the world will all
benefit from this activity.
Fogarty is essential for building these international
collaborations and we work very closely with NIA and with other
institutes at NIH to do this important international
Thank you very much.
[The prepared statement of Dr. Bernard and Dr. Glass
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Mr. Smith. Dr. Glass, thank you very much for your
testimony and your leadership as well.
Let me just ask the question with regards to imaging, which
you mentioned a moment ago, Doctor. What kind of brain imaging
are we talking about? CAT scan? MRI?
Obviously, that is not available in most developing world
settings, and since there is such a under--large numbers of
people never get a diagnosis--about 50 percent or less in the
United States--how quickly is this technology being advanced so
more people will get a definitive word earlier on so some of
these drugs that, again, only deal with symptoms can be applied
to mitigate those symptoms?
Dr. Bernard. So what I was describing as opportunities with
imaging and looking at proteins are meant to be in the research
But they are being refined and we are beginning to look at
things in the blood--in the peripheral blood. We are looking at
things like changes in smell.
We are looking at things like the development of depression
symptoms years before a person actually has dementia as things
that will help us to be more precise in making that diagnosis
So it all comes together to help us. We don't quite have
something that can be translated directly from the research lab
that is anything better than we currently have in terms of
looking for symptoms right now.
Mr. Smith. Just let me ask you, Dr. Glass, about Uganda and
the situation with hydrocephalic condition.
I have had five hearings on that. We have a bill that would
address that need and we actually had doctors--Dr. Benjamin
Warf, who developed a non-shunt intervention to help people who
have water on the brain, and it is amazingly effective and not
much by way of having to redo it.
You mentioned risk factors. Obviously, genetics is a risk
factor. We all know that, and one of those studies you
mentioned, that's a big focus.
But when you talk about environmental risk factors, we know
that in the area of autism environment does play a very serious
role, and NIH has chronicled that in its reports.
I am wondering if other areas of investigation are being
pursued including toxic chemicals of various kinds. Lyme
disease--I chair the Lyme disease caucus as well and it's a
huge problem in my district, in my state, and in our region--is
grossly under reported, and there have been studies that found
that people with Lyme that dementia was one of the
consequences, and I am wondering if that's being looked at.
So maybe if you could speak to the environmental side of
it, if you would.
Dr. Bernard. So I will start off and say that from the
environmental perspective, yes, we have a number of studies
that are looking at various environmental toxins that may be
contributing to problems with the development of Alzheimer's
that's particularly assisted by projects that are looking at
people in the long term and looking at what has happened to
We are also looking at education, looking at diet, looking
at geographic location. All of those may contribute. I quite
honestly do not know specifically about Lyme disease. We could
look back and get back to you on that.
But a variety of things environmentally and socially seem
to be associated with differences in the frequency with which
various groups have Alzheimer's disease.
Mr. Smith. Dr. Glass, do you want to add anything?
Dr. Glass. I don't know of other risk factors for
Alzheimer's, although Hispanics have an increased risk and an
But for other neurological diseases, we know a lot of about
infections like malaria and other meningitities. We know about
heavy metals and exposures.
We know about foods in Africa, for instance, like manihot,
which has a cyanide that leads to poisoning, and alcohol, of
course, and fetal alcohol.
So there are other toxins. But for Alzheimer's we don't
have those yet and we could look into and provide that
Mr. Smith. I'd appreciate that, for the record.
The international response has become increasingly
aggressive and robust. In 2012, the WHO released a document,
``Dementia: A Public Health Priority,'' and I and Greg Simpkins
and others on our subcommittee met with Dr. Margaret Chan, a
former WHO director general and she had a real heart for this
as do so many others at the WHO.
In 2013, the G8--now G7 without Russia--but the G8
committed to more research funding, and that is Canada, France,
Germany, Italy, Japan, Russia, the United Kingdom, and, of
course, the United States.
And I am wondering if you could tell us that plus the
newest 2017 WHO action plan. PAHO--the Pan-American Health
Organization--has a plan. People seem to be coming up with
action plans, and that's all great, but how well are they being
Are the other countries, for example, like us--we are
tripling our NIH funding. It's a bipartisan effort. Again, I
mentioned Tom Cole, the chairman who's doing a wonderful job.
He's got a heart for this.
The Alzheimer's Association never lets up in pushing this
and having a great impact.
In my own State, Christine Hopkins is the Alzheimer's
Ambassador. We all have one. She is constantly in contact with
me and I think that is a great way of advocating on behalf of
patients and caregivers.
Katie Macklin is the director in our area and I was just at
a march for Alzheimer's in Bradley Beach. There was over 1,000
people. So the Alzheimer's Association are here and they will
be submitting testimony as well.
We are really pushing for the private sector to come up
with money augmented, of course, and leveraged by the public
Are the others doing it as well? Is Japan, is Germany, the
U.K., the other G8--the more affluent countries coming up with
the resources so synergistically we'll see a great surge in
Dr. Bernard. So I can certainly say that we track what's
happening internationally and something that was developed
jointly with the Alzheimer's Association is something called
the International Alzheimer's Disease Research Portfolio that
allows us to see across the globe what is going on.
It currently has more than 8,000 projects representing 30
funding agencies, 11 different countries. We also work through
the department in being responsive to what the World Health
Organization is doing to work across the globe in Alzheimer's
projects and we are aware that various countries have developed
plans as we have. So I will probably defer to my colleague, Dr.
Glass, for further elaboration.
Dr. Glass. The most important risk factor for Alzheimer's
is age. We see an aging of the population around the world,
which is why this has become such a tremendous problem, as we
look forward, and I think it's because of that aging that many
groups including the Japanese and the English have invested in
I think as new diagnostic methods become available so you
can actually make a proper diagnosis, the importance of
Alzheimer's globally will be observed in each of the countries
that does the surveys.
And so with the improvement of diagnostics that don't
require a dead brain, we'll be able to understand the
prevalence and increasing incidence over time.
Mr. Smith. Just two final questions. Is there a best
estimate if things don't change where we will be by 2025 and
2050? I gave one estimate and there's highs and lows, of
course. They were all guesstimates.
Do you think we will reach the goal of a disease-modifying
therapy by 2025, which was the G8 push, which is the WHO push,
which is our push with NAPA, the bill, that we all got behind
and pushed a couple of years ago? Do you think we will get
there? I mean, is there enough critical mass of resources to
get us there, in your opinion?
Dr. Bernard. I was going to say that we are very grateful
for the additional resources that have been provided and,
again, as a clinician, I am really excited because there has
been the opportunity to invest broadly in basic research
that'll help us to better understand what's happening
mechanistically with this illness, an explosion of recognition
of genes that are related to it.
We went from only knowing four genes a little more than a
decade ago to more than 24. Lots of clinical studies, 100 or
so, with results coming out in the next many years that'll help
us to understand which direction we need to go.
Enhancement of population-based studies that'll help to
answer some of the questions that you were asking about toxic
exposures, social factors, et cetera.
So I think that there's great momentum going on and we'll
have to see.
Dr. Glass. I would concur. You know, we have more tools to
research Alzheimer's today than we've ever had when my dad
passed away. We have imaging techniques, which are
extraordinary, genetic entrees to the disease, animal models
for Alzheimer's that allow us to test out new drugs.
And so we are in a position better today than ever before
to accelerate the advances. The fact that we have so many
monoclonals in clinical trials and drugs that are being tested
could--if any of them delay the progression of the disease they
will have a huge impact on the cost of care.
So I think in the short run we have clinical trials that
are ongoing now. Also, the trial in Colombia--if it's
successful we will all benefit.
If it fails, it will tell us that we are barking up the
wrong tree and we need to find other targets that would be more
susceptible to--for new drugs. So either way, I think we are on
a roll that we've never had before and the opportunities are
clearly before us.
Mr. Smith. As I mentioned in my opening, I will be
reintroducing the Global Brain Health bill next week. It deals
with three diseases: Autism, Alzheimer's and hydrocephalic
condition, referencing what you mentioned about Uganda, Dr.
Dr. Glass. Yes.
Mr. Smith. It concerns me that USAID, and I have had
conversations with Mark Green, the new administrator. It's
important that we do infectious diseases, communicable
diseases, but brain health has been left to CDC and to the
diplomacy area, not to the actual assistance at the country
So my hope is that we will be able to get this bill passed
and begin moving in the direction of funding--those kinds of
initiatives as well.
Mr. Bera. Thank you, Mr. Chairman.
Dr. Bernard, you talked about longitudinally following
older Americans and so forth.
Is--as you are building this database and looking at that
database and now adding in folks from around the world as well
in that database, what kind of patterns are--has it been around
long enough and what types of patterns, potentially, are
Dr. Bernard. Thank you for asking that question, because
what we are seeing is, in the United States, at least, that the
incidence of Alzheimer's disease may be decreasing in certain
segments of the population.
Whether that is because of better education, better blood
pressure control, better nutrition, we don't know. But we are
seeing other sorts of things like we are being able to
determine that if you make it to age 70 without cognitive
impairment that you still have, as a man, a almost one out of
four chance of developing Alzheimer's, as a woman a one out of
three chance of developing Alzheimer's disease, and we are
seeing--when we compare across countries that there seems to be
a socioeconomic status relationship.
You know, the higher the socioeconomic status, the longer
one puts off the likelihood of developing an Alzheimer's type
dementia. So there is, clearly, a social component to this and
we are looking forward to further disentangling that.
Mr. Bera. Do you see a pattern with level of educational
attainment? So, you know, lower rates of Alzheimer's disease in
folks with higher educational attainment?
Dr. Bernard. It appears that that there is such a
correlation--that the rate of the development of the disease,
the age at which one develops the disease is--the rate is
The age at which you develop is older. So there seems to
perhaps be some sort of protective or beneficial effect of
Mr. Bera. So when I used to practice medicine, I would tell
my patients to do crossword puzzles every day. It wasn't--just
something that I was telling them to do in terms of exercising
your brain and go into distant memories and----
Dr. Bernard. Yes. Yes. We have a number of studies where we
are trying to really disentangle exactly what makes the
difference. Whether it's doing crossword puzzles or the brain
games are out there, et cetera, we don't have definitive
evidence that that's truly impactful.
We do have one study, something called the Active Study,
that demonstrated that if you trained people in a particular
component of cognition that that was beneficial for that
component like speed of processing of information or memory or
things like that.
But it's not clear that it truly can put off dementia. In
fact, we had the Agency of Health Research and Quality and the
National Academy of Science, Engineering, and Medicine to look
at that very carefully for us recently and they--their
assessment was that we are not yet at the point that we can say
definitively that those things that we recommended for patients
are going to make a difference.
But it certainly can't be harmful and particularly if
they're enjoying those sorts of things. I do the same sort of
thing as well.
Mr. Bera. Dr. Glass, do you want to add anything in
addition to that?
Again, you know, as we--as we do when we do medical
research we are creating this huge database and we are looking
In terms of risk stratification now and, you know, as, you
know, we try to come up with better diagnostic tools, what are
some of the, you know, outside of family history of Alzheimer's
what are some of the risk factors that we ought to be thinking
about and educating the public on and, certainly, educating our
physicians on as well in our workforce?
Dr. Bernard. So, certainly, it appears that people who are
likely to develop an Alzheimer's type dementia are the people
who live for a longer period of time, the people who may not
have as high a level of education, people who have had problems
with high blood pressure and diabetes and that's the reason
some of the populations that are considered to be under
represented populations in the United States may have a higher
prevalence, as Dr. Glass alluded to.
There may be some role for past significant head trauma--
things of that sort. But, you know----
Mr. Bera. We are not--we still haven't quite seen
definitely those patterns emerge out of the--out of the
Dr. Bernard. There are risk factors that we've seen.
Whether they are modifiable risk factors is the--is the
Dr. Glass. Let me just add, Congressman Bera--Dr. Bera--
even with in the Colombia cohort, which comes from a single
founder, there are genetic mutations that have been introduced
over the last 200 years so that the age of onset, the speed of
progression, are all idiosyncrasies--differences that we can
understand by linking the genetics with the phenotype and with
So we can actually learn a lot about the genetics by
plotting those individuals. So I think there's--when we deal
with the melting pot of the United States with genes that have
been mixed from all over, much more difficult to do and I think
that we'll learn a lot more from this cohort and perhaps from
others, which have these familial modifications.
Mr. Bera. Dr. Bernard, with a family history of Alzheimer's
disease, what is the risk of developing Alzheimer's disease?
Can we say definitively or----
Dr. Bernard. What we can say is that if you have an APOE 4
gene or two versions of the APOE 4 gene that you have a very
high risk. We can't say there's 100 percent likelihood but a
very high risk of developing Alzheimer's disease.
If you have an amyloid precursor protein mutation
presenilin one or presenilin two, those are associated with
early onset Alzheimer's disease.
They tend to be autosomal dominant, meaning that very
likely you are going to develop Alzheimer's disease associated
with that. That's with the Colombian cohort. And then just
simply a family history, yes.
I mean, if you have family members who've had an
Alzheimer's type dementia you may be at greater risk as well.
Whether it's related to one of those other genes that we've
discovered of late or a combination of the genes or
environmental factors or social factors, not totally clear at
Mr. Bera. And in terms of risk stratification, so patient
presents with a family history of Alzheimer's disease, how
readily available are the genetic testing and, you know, again,
just to try to think about risk stratify?
Dr. Bernard. So I think that there are private entities
that are available that can do the genetic testing. We
certainly have a system--Alzheimer's disease centers that are
set up to bring people in to participate in research programs
and some of these centers are focusing on people who have
And I would again put a plug in for people to be involved
with such things because we need lots of different people--a
diversity of people involved in these studies to really
understand what--how is it going to present in different
Mr. Bera. And do we know, are there any prospective studies
going on right now where you are taking folks with a confirmed
diagnosis of Alzheimer's type dementia, taking--taking their
family members and prospectively following those family
members, looking for patterns? Are those studies ongoing?
Dr. Bernard. So we have a number of studies that are
looking at people who, by biomarkers--you know, they have the
changes in the brain, they may have a genetic abnormality but
they are not yet symptomatic--and we are looking at various
interventions to try to make a difference in their outcomes. So
to that degree, yes.
Mr. Bera. Now, and at this stage with what we do know,
there's nothing that prevents us from educating our health care
If someone has that family history of Alzheimer's disease,
you know, they ought to look at those other mitigating
factors--manage their diabetes a little bit better, you know,
look at those other lifestyle changes, you know, look at
alcohol consumption and, you know, again, those other
mitigating factors that may not prevent them from developing
Alzheimer's but may slow down the evolution of the disease,
look at maintaining brain activity through, you know, whether
it is, you know, brain games or crossword puzzles or, you know,
maintaining physical well-being--those are all reasonable
interventions that we can do at--probably have a cost benefit
but also, you know--is that an accurate statement?
Dr. Bernard. I think that's a fair statement--that National
Academies and Agency Research and Quality Study that I
referenced they said that we do not yet have definitive
evidence but there's encouraging though inconclusive evidence
that controlling blood pressure and hypertension, physical
activity can make a difference and inconclusive but possibility
of cognitive engagement.
So yes, I would hope that my colleagues, your colleagues,
would do all of the things that you'd mentioned as well as
encourage those patients to think about getting involved in a
Mr. Bera. Great. I could ask 100 more questions but I will
yield back. Thank you.
Mr. Smith. Mr. Donovan.
Mr. Donovan. Well, now that Dr. Bera has made Dr. Glass and
myself feel real comfortable about asking about family history
of two people who have Alzheimer's patients as parents--no,
thank you, Doc. This entire process is an education for me.
And I wanted to ask about--we are talking about studies and
being able to diagnose, and Dr. Bernard, I remember when they'd
say you needed an autopsy to actually do a diagnosis. I
Are we advancing also in how we are treating patients now
with Alzheimer's as we are waiting for the studies to conclude
and how advanced have we gone?
I can't believe what you said in your testimony about, I
think, identifying four genes 10 years ago or so. Now we could
identify 24. That's an incredible advancement for the person on
the panel who's not a physician.
So has our treatment gotten better as your studies have
advanced and developed?
Dr. Bernard. So we, unfortunately, do not have a true
treatment. We have drugs that can slow down symptoms for a
period of time but it really doesn't change the course of the
So at the same time that we are vigorously looking for that
prevention or a cure, we are also supporting research that's
looking at being more effective at caring for the individual
with Alzheimer's disease and for their caregiver.
In fact, on the NIH campus just last month there was a
summit on Alzheimer's caregiving with some 500-plus
researchers, advocates, people living with dementia, and it was
really edifying to hear them reviewing what's there and noting
that we have a lot of interventions that are effective and can
There are opportunities for further enhancements there.
Some 450 recommendations came from that study. So we are
sifting through that and seeing what we can do to further
But I would like to think that we are further down the road
in terms of paying attention to issues of caring for
individuals with Alzheimer's and for their caregivers. There is
still room for further improvement.
Mr. Donovan. Anything to add, Doctor? I am sorry.
Dr. Glass. Not really.
Mr. Donovan. Okay.
Dr. Glass. It would be nice that we had a cure. There are
certainly cultural differences in giving care and keeping
people at home versus in institutions--definitions that people
And we have supported research on caregivers in the Spanish
language because the way you make a clinical diagnosis based on
history is linked to the terms that are used for dementia and
for acceptance of the disease and I think that's an area where
we are learning.
But not breakthroughs as such, just in the care giving--
quality of care giving.
Mr. Donovan. I certainly understand that. I mean, my mother
suffered for 4 years, as I said. A woman from Trinidad and a
woman from Ghana treated my mother like she was their own
mother for 4 years.
These people became part of our family. We still have
Thanksgiving with these two women and my mother passed 2 years
ago. And the toll that takes on people--it was almost like at
some point my mother had this innocence about her.
She didn't understand what was going on with her body and
her mind. It was everybody around her who were suffering. So
the emphasis, and Dr. Bera said it too--the recognition and
focus on some of the caregivers of Alzheimer's patients I think
is just as important as caring for the patient.
When you are successful and we do develop a treatment or a
cure, another one of my fears is that as we--I spoke earlier
about global health with maternal health and child health or
even prenatal health, is that we are not getting those things
that we actually do have now here for our children to some of
those developing countries--those folks who are--don't have the
resources we have, and I suspect we'll probably have the same
problem after your success in finding treatments and cures for
Alzheimer's of getting whatever is developed to folks in less
developed areas of our world and do you see that as something
that--I know we have to concentrate on first finding the
treatment and the cure but once we do, getting it to folks
outside of our own country I suspect the folks in our own
country for the most part anyhow will--this will be more
readily available to them than places in other parts of our
So as we see with immunizations for children or prenatal
care from mom, my fear is that after you are successful we
might have the same problem getting the resources to the folks
who need them outside of our own country. Do you see that as an
Dr. Glass. I will make two comments. I thought it was very
thoughtful about your mother and I think part of the issue in
care giving is how do we train caregivers to give the quality
of care that your mother got from these two women.
My father was in exactly the same situation and that
quality of care and how we train people to provide this is
essential. Some of this we can learn through global
On the other part of your question, can the interventions
that we develop in the United States be carried abroad? We have
a whole agenda at Fogarty on implementation science--of taking
what we've learned and implementing it in developing countries.
We have learned, for instance, how to prevent mother-to-
child transmission of HIV. But in many countries this has not
reached all the pregnancies and mothers, and if you miss a
pregnancy, you'll have a child born with HIV who will need
treatment for life.
So in the area of implementation strategies, that has
really become a priority for our research of taking what we've
learned and implementing in developing countries.
I think, Chairman Smith, one other thought I--since you
mentioned Dr. Warf, one of the values of global health research
from his research is that he developed methods to treat
hydrocephalus without needing to revise shunts every few years
in children in developing countries because you can't take them
in for repeat surgery.
So through two procedures that he's adapted that were known
but mixed together, one to open the outflow of cerebral spinal
fluid, the other to cauterize the choroid plexus that produces
CSF--the spinal fluid--he could decrease the flow, increase the
outflow, decrease the input, and so he could do a single
operation without the revision.
That operation is now being used in the United States to
treat our children with hydrocephalus. So it's through that
research done in Uganda by an outstanding American
neurosurgeon, seeing the need in that country to bring that
technology home to our own children, it is another benefit of,
I would say, reverse technology transfer--learning from the
developing world these kinds of lessons.
It will make American children survive better with
hydrocephalus as well.
Mr. Donovan. Since everyone mentioned a doctor, and you are
the only two doctors that I know besides Dr. Bera, Tony Fauci
is a friend and I remember him saying at one of our conferences
that if you are successful finding a cure for Alzheimer's, the
amount of money that we gave NIH in the 21st Century Cures Act
it will pay for itself, the amount of money we spend on
treating this disease.
I thank you both for your work. Besides being here today, I
thank you both for your work--the people who will benefit once
you are successful.
Thank you all.
Mr. Smith. Thank you, Dan.
Let me just conclude and ask you, if you could--the 2017
WHO Action Plan--on November 13th we know the Bill and Melinda
Gates Foundation and now it's $100 million for Alzheimer's
research--the U.N. itself has established a Global Dementia
Observatory to collate and disseminate key dementia data from
member states to support evidence-based service planning and
strengthening of policies as well as health and social care
What is your opinion of the WHO Action Plan? The steps,
obviously, are a whole of government approach for ourselves.
Are you happy with it? Do you feel that this is really going to
Dr. Glass. First of all, we were delighted to hear about
the Gates contribution to Alzheimer's, and I think as Bill and
Melinda Gates age, they realize that this a risk that's before
them as well.
So their investment is really appreciated and shows a
broadening of global interest in this--in this endeavor. I
think the fact that the U.N. has a Global Action Plan is also
wonderful recognition of the importance of this problem
globally and it remains to be seen how this will be rolled out.
But the fact that it's there and it's recognized and it's
recognized by so many international partners is an awakening to
the--to the importance of the burden of this disease for all of
Mr. Smith. Thank you.
Dr. Bernard. I would just support what my colleague has
said. We think that this is something that needs all the best
and brightest minds put toward it and what we have observed is
that as other countries are putting resources toward it, there
are more and more scientists with whom we can collaborate and
that's only to the good of all.
Mr. Smith. Thank you for your leadership. Thank you for
being here today. Is there anything else you'd like to add
before we go to panel two?
Thank you so very much.
I would like to now welcome to the witness table our second
panel, beginning with Dr. Mary Mittelman, who serves as
research professor at the Department of Psychiatry and
Rehabilitative Medicine, and director at NYU Alzheimer's
Disease and Related Dementias Family Support Program at NYU's
School of Medicine and the Langone Health at NYU.
Dr. Mittelman was principal investigator of a randomized
controlled trial of the NYU caregiver intervention funded for
20 years by the National Institutes of Health, the results of
which have been published widely.
Dr. Mittelman has expanded her research focus to
interventions that include the person with dementia as well as
the caregiver. She's the founder of the Unforgettables, a
chorus of people with dementia and their family members, which
rehearses and gives regular concerts in New York City.
We will then hear from Dr. Richard Mohs, who is the chief
scientific officer for the Global Alzheimer's Platform--GAP--
Foundation, a patient-centered nonprofit organization devoted
to enhancing the speed and quality with which new treatments
for Alzheimer's disease are developed.
He retired in 2015 from Eli Lilly and Company where he held
several leadership positions including VP for neuroscience
early clinical development and leader of the Global Alzheimer's
Drug Development Team.
He also serves as a member of the Board of Governors for
the Alzheimer's Drug Discovery Foundation, a member of the
board of directors of Cogstate Limited based in Melbourne,
Australia, and senior associate editor for Alzheimer's and
Dementia, the journal of the Alzheimer's Association.
Then we will hear from Michael Splaine, who is owner and
principal at Splaine Consulting, a small advocacy and
government affairs consulting firm with a very big impact based
in Washington, DC.
Immediately prior to starting the company he was Director
of State Government Affairs in the Public Policy Division of
the Alzheimer's Association, leading its grassroots network to
accomplish State policy priorities including comprehensive
State Alzheimer's plans.
Well known as an advocacy trainer and grassroots organizer,
Mr. Splaine has also been faculty for Alzheimer's Disease
International University public policy and is active in ADI's
World Health Organization's Strategy Group and is now advancing
its policy agenda with U.N.-based opportunities in New York and
Thank you all for being here and please, Dr. Mittelman, if
you would begin.
STATEMENT OF MARY MITTELMAN, DR.P.H., RESEARCH PROFESSOR,
ALZHEIMER'S DISEASE AND RELATED DEMENTIAS FAMILY SUPPORT
PROGRAM, NEW YORK UNIVERSITY
Ms. Mittelman. Thank you. I got into this field because my
mother had dementia. I am trained as a psychiatric
epidemiologist and when my mother had dementia my family really
did not cope very well. In fact, the dementia probably drove us
apart rather than bringing us together.
And after she died, I decided to try to figure out whether
there was a way to help families like mine to cope better with
And I was lucky enough to meet four women who were working
at NYU, helping caregivers as volunteers and I--and I saw what
they were doing and I decided to try to write a--to run a
clinical trial of what they were doing.
So I wrote a grant proposal to the NIMH and was funded from
1987 to 2010, ultimately, by the NIMH and the NIA to study an
intervention that was based on what these women had been doing
The intervention, which we subsequently named the NYU
Caregiver Intervention, is a multi-component intervention and
it is individualized to the needs of every caregiver. It starts
with a comprehensive assessment of the primary caregiver and
then there is an individual counselling session, the point of
which is to help the caregiver to understand the need--her need
or his need for support from other family members, friends, and
And then there are four family counselling sessions with
family members that the caregiver nominates as important to him
or her and a final individual session.
So there are six counselling sessions in a period of 4
months. But since Alzheimer's disease can last as long as 20
years in an otherwise healthy person, we thought it was
important to provide ongoing support.
So other parts of the intervention that provide ongoing
support are recommendations that the caregiver join a support
group that's run by the Alzheimer's Association or other
organizations like it and also we were available for what we
named ad hoc counselling.
So any caregiver or family member who participated in our
study was able to call the counselor at any time for as long as
they stayed in the study and some caregivers actually stayed in
the study for more than 18 years.
So in that time I was--in the time I was funded and because
people stayed in the study for so long, I was able to
demonstrate incredible benefits of this intervention compared
to the usual care that people were able to get at NYU at the
And, basically, the most important component that was not
available to the control group in our original randomized
control trial was the family counselling.
So we think the family counselling was the key and most
important ingredient in this package in the multi-component
So what were some of the benefits that we were able to
demonstrate? We were able to show that family--the first thing
that happened was that the primary caregiver was more satisfied
with the support that he or she got from family members and
This then led to significantly reduced symptoms of
depression, significantly reduced symptoms of stress, improved
caregiver physical health, and by those--by those changes all
through improving family support for the primary caregiver we
were able to keep the person with dementia at home on average a
year and a half longer than the people who got our usual care.
So this is a really powerful intervention and its--and its
power is through social support. More recently, we were able to
show that this intervention could safe huge costs to the health
care system in a study that we published in Health Affairs in
We showed that the State of Minnesota with a population of
about 5.5 million people could, if every caregiver got the NYU
caregiver intervention, save $996 million in 15 years.
That factoid, not all the other things I told you about--
depression and stress and physical health--but that fact was
brought to the attention of the governor of the State of New
York who, because of it, allocated $75 million to family
support programs of which now I am running one.
And I think--and our program is really, while we would have
to do what is mandated by the State, is really--the core of it
is improving social support for the family caregiver.
And I think that everything that we've done has been about
social support and that is something which doesn't cost
necessarily a lot of money and I think in any country that
could--that would want to learn how to would want health care
providers to learn how to do this intervention.
It could be done at a relatively low cost and in developing
costs often labor is cheap and pharmaceutical interventions may
be very expensive.
So because of our--of our success, even before the Health
Affairs article, people in other countries were interested in
doing the study.
We did the three-country study in the U.S., the U.K., and
Australia, which replicated our findings of reduced depression
in caregivers even though all of the people in the study--all
the patients in the study were getting Donepezil, which was an
approved drug for dementia.
We have done a study in Israel that showed similar findings
and we did a study in--we are currently doing a--finishing a
study in Spanish Harlem, which is showing the effects, again,
of this intervention.
So I am here to say that there is something right now that
works--that it isn't a drug and it won't cure the disease but I
can help people to live better with the disease, and I think
that while we are waiting for an intervention--a pharmaceutical
intervention, it is incumbent upon all societies to do the best
they can to improve the quality of life of family caregivers
and people with dementia.
So some of the more recent interventions that I am involved
with you mentioned the chorus, which I founded in 2011, is a
very relatively inexpensive intervention. People with dementia
sing with their family members.
They rehearse for concerts and they give concerts. They
learn new songs, which is something nobody believed could
happen. So people with dementia are learning 18 new songs for
every concert, not only giving pleasure to themselves, not only
finding support with other people like themselves, but giving
pleasure to the community.
So I think that what we can do right now is to improve
social support for family caregivers and for people with
[The prepared statement of Ms. Mittelman follows:]
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Mr. Smith. Thank you, Dr. Mittelman. That is so
encouraging, and thank you for your leadership and for
providing this subcommittee with those insights.
I would like to put that article, if you would. We could
find it and make it a part of the record because that would----
Ms. Mittelman. The Health Affairs article?
Mr. Smith. Yes.
Ms. Mittelman. Okay. Yes, I have the list--there is a list
in my testimony of all the articles but I am happy to send it
Mr. Smith. Great. Thank you. We will look it up and
download it and put it in. Thank you.
STATEMENT OF RICHARD MOHS, PH.D., CHIEF SCIENTIFIC OFFICER,
GLOBAL ALZHEIMER'S PLATFORM FOUNDATION
Mr. Mohs. Thank you, Chairman Smith. Thank you for inviting
me. It's a real pleasure especially to follow Dr. Mittelman.
Most of my career has been devoted to trying to develop new
medicines for Alzheimer's disease and I wish I could report
that we had been more successful up to now.
But I can tell you what we've been trying to do and give
you some thoughts about how we could maybe make that happen
faster. But medicine alone is not the answer and so the
programs that Dr. Mittelman and people like her are developing
are going to be an integral part of the management program for
dementia forever, essentially.
So the Global Alzheimer's Platform Foundation for which I
now work is a not for profit organization, was founded by
patient advocates to help speed the completion of high-quality
clinical trials of potential new therapies for treating and
preventing Alzheimer's disease.
It is the belief of GAP's founders, primarily George and
Trish Vradenburg, along with John Dwyer, that only through
rapid and rigorous testing of potential new treatments we will
be--will we be able to make progress in alleviating the
suffering caused by Alzheimer's disease.
The foundation has worked with academic investigators,
government agencies, pharmaceutical companies, and other
organizations similar to GAP outside the United States to
develop networks of clinical trial sites that conduct--that can
conduct studies quickly and with high quality.
GAP has found eager partners for our efforts in the
European Union where there is something called the EPAD Network
for the European Prodromal Alzheimer's Disease network, and
Japan has a JPAD network, Australia has an APAD network, and we
have partnerships developing in other regions around the globe.
Before joining GAP, I was for 14 years, as was mentioned,
at Eli Lilly and Company where I was responsible for clinical
testing of several potential new medicines for Alzheimer's
disease including two that reach large global late phase
Before Lilly, of course, I had an academic career in New
York at Mount Sinai School of Medicine where we also did
smaller scale studies.
Both of the compounds at Lilly that reached late phase
testing were very promising scientifically. They actually did
address some aspects of what is called the amyloid cascade
hypothesis. But neither showed sufficient efficacy to enable
registration as actual medicines for prescription.
The four-phase three trials that we did--there is usually
two phase three trials for each new potential medicine--
included a total of 4,694 patients with mild to moderate
Alzheimer's disease and these were conducted in 31 countries
Approximately 40 percent of those seen were seen at
clinical sites in North America, 21 percent at sites in western
Europe, 10 percent at sites in Japan, 9 percent at sites in
Mexico and South America, 8 percent at sites in eastern Europe
including Russia, 7 percent at Asian countries outside of
Japan, and 5 percent in South Africa and Australia.
From these experiences with GAP and Lilly and a lot of
years trying to develop new medicines, I'd like to share the
following observations about the global burden of disease and
give you some thoughts about how I think the process of
medicine development might be made a little better.
First of all, in all the countries where GAP and Lilly have
worked we found a high degree of interest in cooperation from
clinicians, health authorities, regulators, patients, and
It is not difficult if you go into any of these countries
to find people who are concerned about Alzheimer's disease and
who are eager to contribute in some way to try and develop a
treatment. It is just a matter of trying to show them what it
is they can do.
I would say that in spite of their limited efficacy, the
currently approved medicines for Alzheimer's disease are pretty
widely used globally.
We were, of course, testing our therapies as add-on to
standard of care--standard of care, which in most countries did
include the already approved medicines, even though they have
limited efficacy, and what we found was that in North America,
western Europe, and Japan over 90 percent of all the study
patients that we found who had a diagnosis of Alzheimer's
disease were already receiving an AD medication.
But in every country where we went it was over 70 percent.
I don't say that this is typical of everybody in that country
because there are a lot of undiagnosed people. But they are
available and they are used.
It was interesting relative to Dr. Mittelman's presentation
that the primary care givers assisting patients with AD as they
navigated through the clinical trials process varied by region.
That is required because these people have some impairment
that every study participant has to have a care giver or
somebody who comes with them to participate in the study.
In North America, western Europe, South Africa, Australia,
and Japan, it was usually primary care givers were spouses--
about 70 percent in all those regions--while in the other
regions--eastern Europe, other Asian countries, and Mexico/
South America, the primarily care givers were much more likely
to be adult children or some other neighbor or person involved
with the patient.
Now I move on to some issues and I think it's clear from
what we heard earlier from the first panel we have learned a
lot about Alzheimer's disease. There are a lot of
opportunities, but this is a tough nut to crack,
I have spent 40 years at it and there are a lot of smart
people out there working at it very hard every day. But it's
proved to be hard. So I'd like to just give you a couple
observations about how the system I think could be a little bit
I think developing drug candidate molecules for clinical
testing based on new biological findings about AD could be
faster. Basically, when you find some new bit of biology, the
therapeutic implications are not always obvious and it takes
somebody who knows about what a medicine has to look like to
make that translation.
I think policies that facilitate communication and
collaboration of academic scientists with those in the
biopharmaceutical industry could be helpful to enable more
rapid discovery of high-quality clinical candidate molecules
accompanied by the biomarkers and other kinds of technology
that's necessary to do clinical testing.
If you just take the history of our drugs to date, the
cholinergic deficiency in Alzheimer's disease was found in
The first cholinergic therapy was not approved until 20
years later and that was a well-known area of biology. What we
know about A beta or amyloid, the structure of that protein was
originally discovered in 1986. We still do not have an A beta-
related therapy, although we have tried but it's a tough nut.
I think also the conduct of clinical trials could be
faster. Streamlining processes of study review, contracting
with sites, review by ethics committees, and site certification
could reduce time to completing clinical testing.
It is often a bureaucratic nightmare to get these studies
up and running. Granted, this is a human endeavor that will
always have some human elements in it. But I think some of
these are partly manmade problems.
Many current clinical trials are designed for patients who
are not yet demented but have subtle clinical signs or
biomarker evidence that they are at risk for AD. This is a lot
of the current work that's going on on either primary or
The problem is those people are not diagnosed in the
current clinical care environment. We have heard that earlier.
Such patients are not regularly identified in clinical practice
and are very difficult to find for clinical trials.
So if you go out to find them, the epidemiology tells me
there is lots of them out there. We just can't find them
readily for trials, and I think that policies that would
encourage early diagnosis of at-risk patients would speed the
completion of trials as well as provide drug benefit to
So those are my observations. Thank you very much for your
[The prepared statement of Mr. Mohs follows:]
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Mr. Smith. Thank you so much for your testimony and, again,
for your leadership as well. Thank you.
STATEMENT OF MR. MICHAEL SPLAINE, PRINCIPAL, SPLAINE CONSULTING
Mr. Splaine. Good to see you. Thanks for the opportunity to
appear before the subcommittee today. I've been working with
people with Alzheimer's and their families since 1986.
Currently, I am a consultant and since 2011 our consultancy
has served as the policy and advocacy advisor to Alzheimer's
ADI is the global umbrella for over 90 national Alzheimer's
Associations including the U.S. Alzheimer's Association.
Of historical note--and I am a little bit of a historian
because I've been around--this whole panel has been around--it
is worth noting that the U.S. Alzheimer's Association and ADI
share common founders.
In fact, 4 years after the Alzheimer's Association was
established by Jerome Stone and others, they established
Alzheimer's Disease International. So some sense of this being
a global issue was there even in the very beginning in the
Our current work with Alzheimer's Disease International has
put my associate, Kate Gordon, and myself in the middle of a
burst of international energy and work streams that are moving
on the issue of dementia and moving it closer to a public
health priority that experts believe it needs to be.
My plan with limited time is to hit the high points on what
I think are key developments that have not been covered by
The facts are stark, and in the introduction to the
hearing, Mr. Smith kindly cited the facts that I have on record
One possible fact that was not cited by the chairman that
might be of special interest to this subcommittee is the
publication of a report on Alzheimer's disease in sub-Saharan
Africa that is less than 6 weeks old. It was published by ADI.
It estimates that there are 2.13 million persons with
dementia in that region, a number that is expected to roughly
double every 20 years.
Sometimes there's a belief that Alzheimer's can't and
dementia issues can't really be truly global. But with the
publication of that report and the facts therein, I think that
has been put to bed.
Well, let me review some key global developments. First of
all--and there's a graphic in my testimony that kind of tries
to demonstrate this--dementia is increasingly understood to be
a life course disease by policy makers, not merely a disease of
older persons, not merely a condition of complete and utter
disability, although the public perception that a person with
Alzheimer's disease must necessarily be older and quite
disabled and the latter stages of the disease persists.
This opportunity to diagnose early and having early stage
persons involved in many facets of the work is putting a
different face on what it means to live with dementia.
Even further to the left in that curve that you have in
your packet is a representation of what the Lancet Commission
and others have recently found that there is action to be taken
by public health authorities on modifiable risk factors for
Keep in mind that population health personal results may
vary. We are talking about the health of the entire population.
But it's pretty clear it can be summarized simply as what's
good for your heart is good for your brain--is actionable today
by public health authorities and in fact there are many
examples of that going on around the world.
A second important trend or a second important global
development is that we continue to have detection and diagnosis
as a stubborn problem everywhere.
Although cited earlier, let me just repeat what you cited
earlier, which is that without diagnosis there can't be
treatment care and organized support or the opportunity to
participate in research.
I think some of our gap in research is the diagnostic gap
and I think this gap should also be of interest to any health
system as persons with impaired thinking and another chronic
disease are expensive because thinking is important to
navigating complex health decisions and treatment regimens that
are only frequently seen in deep crisis.
Third, I want to mention and in fact already mentioned
before the committee that in the Americas in 2015, PAHO/OPS
adopted a regional dementia action plan and in 2017 just a few
months ago, the World Health Assembly adopted a global dementia
Taking a right spaced approach, these action plans call on
and will provide technical support for national government
plans and policies over the next 5 years to take advantage of
our newer understandings of dementia and to plan nation by
nation a response across the spectrum of the disease.
I note that 30 countries have published national plans and
nearly 100 subnational governments, States, or regional
governments have taken action.
But I will also note that in our view only one country has
taken serious action on dementia without a strong civil society
push. It is almost as if we have a three-legged stool where the
advocacy as well as the knowledge of the issues and advocacy
capacity are important to move forward.
On rights, another subject of great interest to this
committee, let me note that persons with Alzheimer's disease
are in some cases using the Convention on Rights of Persons
with Disabilities as a platform for action on care and support.
Dementia has been a special issue in the Organization for
American States Regional Convention on the rights of older
persons, now out for ratification, and in a regional
declaration on older person's rights by the African Union.
Dementia and its consequences has also been a major topic
in the ongoing work of the U.N. Open Ended Working Group on the
rights of older persons.
Last, and I'll leave the rest to my written testimony, a
broader community of interest in dementia as a social issue is
It is taking many forms such as the organizing of nearly
20,000 young professionals in Indonesia around the issue of
Alzheimer's who don't have family experience, as well as issues
being an agenda item at the World Economic Forum in Davos or
this week at the Salzburg Global Seminar
Also in the wake of the Japanese tsunamis we saw for the
first time disaster authorities paying attention to the problem
of Alzheimer's disease.
Multiple international organizations helped raise awareness
during Alzheimer's Awareness Month, and even Pope Francis made
a major address on World Alzheimer's Day last fall.
It is fair to mention that myriad scientific meetings and
cooperation are increasingly becoming the norm. The world's
largest scientific meeting on Alzheimer's disease is hosted and
will be hosted in our country by the Alzheimer's Association in
Chicago in July.
It will be followed this year immediately by the Annual
Conference of Alzheimer's Disease International, truly a global
As I was preparing this testimony, my last thought is faces
come to mind--faces of families such as my sisters, my Aunt
Lee, my Aunt Marilyn--all Alzheimer's care givers--my mother-
in-law, but also faces of people like Lucien and Lee Yu and
even two women from Yemen who started an Alzheimer's
Association--its fate unknown at this moment--in Yemen.
I also think about researchers in Poland, in the Czech
Republic, all over eastern Europe that I've met and enjoyed
their company. There truly is a global view in my head.
I also can't not mention that I am here today principally
because 13\1/2\ years ago my brother gave me a kidney. So thank
you again, Dan.
I am done.
[The prepared statement of Mr. Splaine follows:]
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Mr. Smith. Mr. Splaine, thank you very much. Thank you to
Let me just ask a couple of questions. Again, you are
leaders. You have made all the difference in the world and I
think your point, Mr. Splaine, about the importance of
advocacy, when people have a message that is well-founded and
they back it up with empirical data it gets action on Capitol
As dysfunctional as people think Congress is these days, we
are getting some very important things done, and I mentioned
earlier a tripling of the NIH funding for Alzheimer's and I do
believe we will get to there with the 2018 HHS appropriations
It is no small achievement. I introduced the Ronald Reagan
Breakthrough Act for years and working alongside of you and
others, and we couldn't get even a markup, and now we are at
the point where the money is actually flowing and we are
talking about a tripling--I should underscore a tripling--since
So that burst that you talked about needs to become a
sustainable surge for the sake of the patients, the families,
the care givers and so thank you for your advocacy, all three
of you, and others who have been instrumental in making all the
I think we don't focus enough on how health systems could
implode over the next 30 years or so. I mean, care givers
deflect a lot of those costs that would be borne, and Dr.
Mittelman, you know better than anyone with your work so often
it's the spouse or it's a daughter or a daughter-in-law that
steps up to the plate to take care of the Alzheimer's patient.
I hope you are going to be able to answer this--whether or
not the WHO new agenda item, the surge that they are making--
the new seven point, which includes in its seven points
providing support for care makers, those living with dementia
care givers, and it's one of their seven points.
Hopefully, they are listening to you and the breakthrough
and landmark work you've done so that they don't have to
reinvent the wheel.
So--yes, please. Could you put on your mic, too?
Ms. Mittelman. I neglected to mention earlier that because
we were so successful in these randomized control trials of
which there had been more than one, we were being asked to
provide training for providers, mostly social workers but also
nurses and people in allied professions, and we were going all
around the world to provide this training, as far as Israel,
Sometimes it was fun but eventually it got to be too much
so we got a grant from the NIH to develop online training. So
now people can receive training on how to provide the
intervention online when they wish.
Only in English and in Australian at the moment but--
American English and Australian--but easily--one could easily
imagine how this training, which includes videos of both role
plays and real cases of family care givers being given the
counseling, could be incredibly valuable, even if people didn't
do the actual NYU care giver intervention as we developed it,
to have the training and to understand how to work with
families to help them to support the primary care giver.
Mr. Smith. How hard is it to access? I mean, can you give
the web address or----
Ms. Mittelman. Well, at the moment it has a cost because it
was developed with an SBIR grant.
Mr. Smith. Okay.
Ms. Mittelman. But it is available and I'd be delighted to
talk to you about it more online or offline. But in addition to
that, we encountered another issue that we thought was worth
developing a solution for, which is the that very often
families are dispersed and there could be a primary care giver
in Miami, Florida and the daughter in New York and the daughter
can't participate--couldn't participate in personal counseling
or--and felt left out of the care. So we developed video--a
video conferencing version of our intervention, which we are
doing a randomized control trial of right now.
But I think of that as a potential for people who live in
other--who have family members who live in other countries.
Perhaps the adult child is living in New York and the parents
are living in China or wherever.
One could use video conferencing potentially in countries
where--and for people who have access to the internet to bring
families together and to provide them and the primary care
giver with the kind of support that they need. So----
Mr. Smith. Is WHO accessing your work?
Ms. Mittelman. Not that I know of but, I mean----
Mr. Splaine. Well, that--I know a little bit about that
work stream at WHO and I think they are not just looking at
made in America programs. I mean, they are the global health
organization and there are many to the level that we accept in
the United States--random clinical trial, peer-reviewed
journal, evidence-based programs that were not invented in the
So I think the task of the very small staff working on
dementia at the World Health Organization--did I say that
Mr. Smith. How small?
Mr. Splaine. That--four, six. I mean, a place where this--
where the United States Government could, frankly, make a real
difference, with a couple of secundments of key people from the
United States to either PAHO or to WHO, which is minuscule
dollars compared to what kind of rich resources we have could
make a huge difference.
But they are compiling and evaluating and not reinventing
the wheel. But the wheel goes both ways. One of the things we
get asked all the time by ADI--representing ADI is can you help
us access evidence-based Portuguese language, Spanish language
programs that were--or Chinese language programs that were
invented and validated in other cultures because that is who we
are dealing with as America ages and changes demographically.
So I think, you know, it's bidirectional. It's multi
directional. I also think that this--you mentioned health
Let me just say the population aging is global and it's
really an opportunity for, from a noncommunicable disease as
well as an aging point of view, it may be a real opportunity
for this committee to insist on or take its own top to bottom
look at how we make investments as a government, as a people,
in global health and take--start to factor in not just the
disease by disease approach but really maybe this whole theme
of noncommunicable diseases, going back again to my testimony
about the linkages between risk factors between brain health
and other health. It might be a real opportunity for the
Mr. Smith. I appreciate that. And the idea of secunding
U.S. personnel, that is a great idea. We will follow up with
you on that one.
Mr. Splaine. Thank you.
Mr. Smith. And please take a look again at our global brain
initiative bill because the idea is that infectious diseases
are horrifyingly prevalent in Africa. But, frankly, with Bush's
PEPFAR program, which is about $5 billion a year, mother to
child transmission ARVs--the pandemic--certainly have been
mitigated, and other diseases such as malaria are being
attacked as they should be. But we leave out brain health,
except for diplomacy at WHO and elsewhere.
You mentioned African countries, $2.1 million--has the AU--
the African Union--been responsive at all, as far as you know?
Mr. Splaine. From a rights perspective, the African Union
is one of only two regions in the world that actually has an
explicit rights policy for older persons and Alzheimer's has
been part of that story because, unfortunately, in some pockets
in Africa, people with Alzheimer's disease are perceived as
witches, demonic, and governments like the Government of Ghana
literally have disrupted these witch camps that were developed
as a way of stashing people who are, clearly disabled from
severe cognitive issues from Alzheimer's disease or other
So I think that there is some visibility. You know, they've
got a lot on their plate. But I think population aging is
becoming better known.
There have been two regional meetings inside of a year of
people interested in doing more about Alzheimer's disease on
the African continent that have included African Union
There is also country by country but also as a region--I
hesitate to say but I think it's one of the most active regions
in organizing around noncommunicable diseases by the
Noncommunicable Disease Alliance and other interested parties
because that is becoming part of the reality of health in the
region as well.
Mr. Smith. Just two final questions. Let me ask, do you
believe that we are on track to, by 2525, get a disease-
modifying treatment or maybe even a cure?
Are other countries like Japan and China, the U.K., coming
forward with sufficient moneys? Particularly on the research
side to have that critical mass Manhattan Project type of
Mr. Mohs. There is no doubt that in the countries that have
a large number of older people, particularly Japan and
certainly China and western Europe, you'll find a lot of money
being devoted to Alzheimer's research.
So I don't think that that is the issue. I think there is a
certain amount of discouragement that comes with lack of more
But it would help if we have these existing international
organizations like WHO and OECD and so forth actually make this
a priority because it gives some credibility to these national
organizations that are trying to do something about this to go
ahead with international cooperation and the perception that
this is really a high priority globally.
Ms. Mittelman. Can I make a comment?
Mr. Smith. Yes, please.
Ms. Mittelman. Well, I think that when there are--when we
are trying to find people to participate in clinical trials of
new drugs, if we have psycho social interventions as well as we
did in the three-country study, there may be more--these trials
may seem more attractive to participants.
Mr. Mohs. I think that is quite true, and it's interesting
that for a brain disease to not more fully recognize the
interplay between psycho social and medical interventions is a
I mean, it's hard for me to imagine in cardiology that they
would think that medicine without exercise and weight control
is going to solve the problem.
But we just have to get an understanding that all these
things have to work together and I think from a patient
acceptability standpoint the psycho social interventions are
much more tangible and immediate and provide a more immediate
benefit for people who participate in these trials.
Mr. Smith. And just the final question--I do have others
that I would like to submit to you--the issue of brain imaging
that we discussed in panel number one, you say there is a
viable diagnostic tool, going forward, particularly for early
Mr. Mohs. Well, we were involved in the development of some
of those early amyloid imaging technologies when I was back in
the pharmaceutical industry and I think it has an assisted a
lot in getting more biologically uniform people entering into
Its role in ordinary clinical practice in the absence of
directly related therapies is much more limited. But there has
been discussions about that.
But it's, clearly, a great advance to have a brain disease
where you can actually see the pathology in life. That's
something we have almost never had for any brain disease in the
Mr. Smith. Mr. Garrett.
Mr. Garrett. Thank you, Chairman Smith, and thank you,
members of the panel. And my apologies--I was in another
committee and we got here as quickly as I could.
I did not imagine that I would have the opportunity in the
Foreign Affairs Committee to discuss Alzheimer's and so I am
delighted that that opportunity has presented itself and I
thank the chairman again.
Now, having said that, I will tell you that you probably
didn't imagine the direction that I am about to go here. I
think it's fair to say that a rising tide lifts all ships. I
know that is a cliche and I would ask rhetorically, because I
don't want to waste your time, whether or not we do medical
research well here in the United States.
I think the answer is yes. Relative to the world, we do a
pretty good job, right?
But the next rhetorical question would be, would the
designation of a particular item as a Schedule One controlled
substance stymie the ability of entities whether government or
private to research said Schedule One controlled substance as
it related to medical uses.
And I think the answer--and if anybody disagrees with me
you are welcome to--you are welcome to chime in. You can
interrupt. But I think the answer has to be yes.
And so, obviously, some of you are probably miles ahead of
me because I am a lawyer, not a doctor, which means you all are
But as I look through a list of medications derived from
plants, I find medications that help with blood pressure, with
malaria, with pain, with dysentery, anti-tumor agents,
diuretics, anti-fungal, sedatives, anesthetics, muscle
relaxants--watch me mispronounce--cholinesterase inhibitors,
right. I mean, and when you look up medical plants you'll find
a list that is literally in the hundreds.
So the question that I have for members of the panel is--
and I am not arguing in the favor of any panacea or any
overarching wonderful solution--but might we be well served to
review in the United States our scheduling of cannabinoids,
whether it's CBD oils extracted from hemp, to allow the
research to be done?
Because as I look for studies that relate to CBD oil and
Alzheimer's specifically I find a lot of them and they all come
from the Netherlands and Australia and Great Britain, et
cetera, and we have essentially tied our own hands behind our
back with what I would argue is an archaic legal structure that
denies the opportunity to find potential cures or at least
aiding elements by virtue of the stigmatization of a particular
So the question is, could we further potentially better
outcomes and at least addressing symptoms if we were to free
the circumstances that currently stymie the private sector and
even public moneys from being used to research cannabinoids?
Mr. Mohs. I don't know that I can give you a complete
answer to that questions. Couple of comments, though. You're
quite correct that many current medicines are--were originally
discovered as extracts from the natural world--from plants or
someplace else--and that has been the case throughout the
history of the development of medicines.
My own view, and I just speak from a couple of companies
that I've worked with, yes, it would be a--certainly a
consideration if a--if you were talking about trying to develop
a scheduled substance as a new medicine. That means you got to
do other studies, allowed use liability and potential harm.
But, you know, we used to have a saying--no side effect, no
drug. So usually medicines have some unwanted effects along
with the desired effects and the important part about any
medicine development program is that you fully understand both
of those so that in the end if the judgement is that their
benefits outweigh the risks that at least that can be approved
with an appropriate labeling of all the benefits and the risks
and it's the nature of a development program that it should
investigate both of those things.
But if your point is that it would be a--weigh kind of
negatively on a company thinking about developing something
where you have this whole other side path of trying to mitigate
the risk, I think the answer is probably yes.
Mr. Garrett. And there is an inherent cost, right, to that
legal sort of----
Mr. Mohs. Sure. There is a cost--more studies, more time,
more potential that you are going to find something. I mean,
you don't want to start out with a--with a potential new
medicine where you know right off the bat that it's got down
sides. I mean, that is----
Mr. Garrett. And there is no arguing, certainly, that there
are down sides. But I think if I am correct--and, again, I am
going to let each one of the members of the panel speak to
this--that CBD oil, particularly hemp extracted, you don't get
high. I mean, it's not even a side effect as it's administered
therapeutically, right? I mean, that is----
Mr. Mohs. I think there are cannabinoid derivatives that
actually do not make you high. That's correct.
Mr. Garrett. Yes, sir. And certainly there are some that
you could--that you could, right? I mean, I am not trying to
tell one side of the story.
But anyway, I'll open the floor to either of you fine folks
to just comment on whether or not it might be easier and
cheaper and more cost effective to study potential positives if
the scheduling regime in the United States were relaxed to
allow more efficient and cheaper and more ready studying.
Ms. Mittelman. Oh, I actually think that one of the
benefits of psycho social interventions is that they have
absolutely no negative side effects. So I would go in the other
If I were going to try to do things that were unusual I
would try to figure out what nonpharmacologic interventions
could have major impact.
For example, to go back to the chorus that we founded,
nobody believed when I started it that people with dementia
could learn new songs, and they are learning new songs.
So this is a medicine that has no potential side effects.
In fact, we did a video of the original chorus and one of the
caregivers said, ``Forget about pills. Just give me this.''
Now, imagine if singing could have a major impact on
learning new songs--could have a major impact on neurologic
function and we don't think about those kinds of interventions.
Mr. Garrett. No, I think what you are saying is brilliant
and I appreciate it. But I am an all-of-the-above kind of guy,
and what might work well for one individual or entity might not
work as well for another.
But what you are doing is commendable and I admire you. I
simply submit that because one things works doesn't mean
another doesn't and I believe we have a regulatory scheme here
that is draconian at best and----
Ms. Mittelman. I agree with you on that, but I think that
what you are talking about is thinking out of the box.
Mr. Garrett. Yes, ma'am. No, again, we are not arguing. We
Mr. Splaine, am I pronouncing it correctly?
Mr. Splaine. Well, I am not a doctor. Don't play one on
television. So a couple of thoughts.
I wonder whether it's--you know, is it Schedule One or are
there other things that prevent this kind of imaginative
thinking about experimenting with these substances.
So a couple of thoughts on that. One is we do have a pretty
strong not invented here ethos in the scientific community and
I think that is made a little bit more challenged because there
is a prevailing theory of Alzheimer's disease in the United
States and in the United States science establishment that
although respected in other countries they are investigating
along different lines.
For example, Mr. Smith, I don't want to correct you except
I will--I would add the Republic of Korea to your list of very
engaged countries about Alzheimer's also from a research point
Their drug mechanisms of action--remember, Alzheimer's has
three parts. It has plaques, tangles, and inflammation. They
are almost completely zeroed in on inflammation and it's
something that is almost completely not ignored but it's not a
mainstream in the United States.
It's attacking the amyloid. So I think that is just
something to think about is the prevailing theory keeping this
out of consideration rather than Schedule One.
Last, our language about Alzheimer's treatments is most
unfortunate in that somewhere in the 1980s we started talking
about disease-modifying drugs and mere symptomatic treatments
and we have minimized social interventions.
We have minimized the drugs we have by calling them mere
symptomatic treatments. I would submit what is insulin? A mere
symptomatic treatment? Yes, but it also--I mean, what do people
want when they live with a disease?
I can tell you first hand as somebody who has lived with
disease, we want treatments that allow us to get on with our
So I think sometimes the language and holding out for--this
is why I get really uncomfortable about will we have a cure by
2025. We have this language we have developed in Alzheimer's
about symptomatic treatment versus disease-modifying treatment
and I think that too is a barrier to people thinking outside
Mr. Garrett. So let me----
Mr. Splaine. So I think it's those other things that are
going on in the Alzheimer's scientific thinking, not so much
that it's a Schedule One problem.
Mr. Garrett. Well, let me--let me--at the indulgence of the
chair very quickly--submit that while we search for a cure in
the interim we should also be searching for treatments, right?
That it's an all-of-the-above, not a--not a one or the other.
And so while we hope one day to move away from fossil
fuels, in the interim we are burning oil as we develop wind and
solar, right. I mean, it's getting from point A to point B.
But let me ask you this, and I am leading intentionally
because I can here--would you not agree that Schedule One
designation inhibits research and makes that more tedious and
costly for those who might be interested in engaging in it? I
Mr. Mohs. I can't----
Mr. Garrett. I was actually addressing that----
Mr. Mohs [continuing]. I have never had--I have never had
any clinical candidate that I was responsible for impeded in
its development by scheduling.
That doesn't mean somebody else might have and, honestly,
in my time in the pharmaceutical industry most of our
interactions with FDA were actually quite helpful. They were
Now, there may be some areas that I didn't get into where
there is some adjustments that need to be made. But I will tell
you, they were--they were actually quite forward thinking in
their treatment about approval processes for Alzheimer's
I think they knew quite well that it was a very bad disease
and were willing to work with any sponsor that came to them
with any reasonable proposal about how to develop a treatment.
Mr. Garrett. But if you want to work with willow bark you
don't need to get Federal Government permission to get the
If you want to work with quinine, you don't need to write--
I mean, anyway, thank you for being here and, again, I am not
suggesting this is a panacea, just that we should get out of
our own way, and thank you all for thinking outside the
But, again, the tact to win this fight I think it's an all
of the above and open minds and look at what works and what
So thank you, Mr. Chairman.
Mr. Smith. Thank you, Mr. Garrett.
I'll just conclude, and any comments you might want to
make, any questions that went unasked please, if you could
provide those answers or just speak to it.
The idea of a goal that we developed with the NAPA bill and
also with the G7 and the WHO Assembly, isn't that it's--it's to
sharpen the mind and to marshal resources, as you know.
That's why I've asked are we on the right path to either
achieve it or come close? Even coming close will be an
I do--Dr. Richard Mohs, you make the point that to develop
truly effective ways to treat, manage, and delay the onset of
Alzheimer's disease will require many studies of potential
medicines, behavioral interventions, patient assistive
technologies, and the combination approaches.
We are doing that, right? Or are we lagging in any of those
Mr. Mohs. We are--we are doing it. I think it could be--as
I mentioned, I think it could be done a little faster. The
scientific uncertainty is still great and so the only way to
tackle that is to accumulate knowledge as fast as you can and
that requires a lot of----
Mr. Smith. Well, how many compounds are being tested as
Mr. Mohs. I think the last we checked there were about 30
something in phase three and in the 60 range in phase two, and
usually companies don't report earlier than that because it's
so iffy back there that it's hardly worth reporting.
But there is a lot, and that doesn't even take into account
all the little labs and so forth around the world. But on
problems like this you need a lot of ideas.
You need a lot of studies to help resolve the uncertainty
about those ideas and the communication from different
laboratories to each other so that they don't repeat and follow
up on unpromising areas is very important.
Mr. Smith. I want to thank you again for your leadership
and for being here today and helping to inform this
subcommittee and, by extension, the U.S. Congress.
And I thank you again. The hearing is adjourned.
[Whereupon, at 4:16 p.m., the subcommittee was adjourned.]
A P P E N D I X
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]