[Senate Hearing 116-538]
[From the U.S. Government Publishing Office]
S. Hrg. 116-538
ALZHEIMER'S AND OTHER COGNITIVE
DISEASES: AN ARIZONA PERSPECTIVE
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HEARING
BEFORE THE
SPECIAL COMMITTEE ON AGING
UNITED STATES SENATE
ONE HUNDRED SIXTEENTH CONGRESS
FIRST SESSION
__________
SCOTTSDALE, ARIZONA
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NOVEMBER 1, 2019
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Serial No. 116-14
Printed for the use of the Special Committee on Aging
[GRAPHIC NOT AVAILABLE IN TIFF FORMAT]
Available via the World Wide Web: http://www.govinfo.gov
__________
U.S. GOVERNMENT PUBLISHING OFFICE
47-206 PDF WASHINGTON : 2022
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SPECIAL COMMITTEE ON AGING
SUSAN M. COLLINS, Maine, Chairman
TIM SCOTT, South Carolina ROBERT P. CASEY, JR., Pennsylvania
RICHARD BURR, North Carolina KIRSTEN E. GILLIBRAND, New York
MARTHA McSALLY, Arizona RICHARD BLUMENTHAL, Connecticut
MARCO RUBIO, Florida ELIZABETH WARREN, Massachusetts
JOSH HAWLEY, Missouri DOUG JONES, Alabama
MIKE BRAUN, Indiana KYRSTEN SINEMA, Arizona
RICK SCOTT, Florida JACKY ROSEN, Nevada
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Sarah Khasawinah, Majority Acting Staff Director
Kathryn Mevis, Minority Staff Director
C O N T E N T S
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Page
Opening Statement of Senator Susan M. Collins, Chairman.......... 1
Opening Statement of Senator Martha McSally...................... 3
PANEL OF WITNESSES
Alireza Atri, Ph.D, Director, Banner Sun Health Research
Institute, Sun City, Arizona................................... 4
Roberta Diaz Brinton, Ph.D, Director, Center for Innovation in
Brain Science, University of Arizona, Tucson, Arizona.......... 7
Lisa Capp, Previous Alzheimer's Disease Caregiver, Phoenix,
Arizona........................................................ 9
APPENDIX
Prepared Witness Statements
Alireza Atri, Ph.D, Director, Banner Sun Health Research
Institute, Sun City, Arizona................................... 31
Roberta Diaz Brinton, Ph.D, Director, Center for Innovation in
Brain Science, University of Arizona, Tucson, Arizona.......... 37
Lisa Capp, Previous Alzheimer's Disease Caregiver, Phoenix,
Arizona........................................................ 40
ALZHEIMER'S AND OTHER COGNITIVE DISEASES: AN ARIZONA PERSPECTIVE
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FRIDAY, NOVEMBER 1, 2019
U.S. Senate,
Special Committee on Aging,
Washington, DC.
The Committee met, pursuant to notice, at 10:15 a.m.,
(MST), at Granite Reef Senior Center, 1700 N. Granite Reef
Road, Scottsdale, Arizona, Hon. Susan Collins, Chairman of the
Committee, presiding.
Present: Senators Collins and McSally.
OPENING STATEMENT OF SENATOR
SUSAN M. COLLINS, CHAIRMAN
The Chairman. The hearing will come to order.
Good morning. What a pleasure it is to be here in Arizona
with my colleague, Senator Martha McSally, to convene this
field hearing of the Senate Special Committee on Aging. Senator
McSally has been a valued and active member of the Senate Aging
Committee, which I chair. Her commitments and contributions to
the Committee's work are many, and today's hearing reflects
Senator McSally's work to advance research and care for
families facing Alzheimer's disease.
As the founder and co-chair of the congressional
Alzheimer's Task Force, this is an issue that is particularly
important to me as well. Many families in our country,
including mine, have been touched by Alzheimer's disease. Just
last year, I lost my father to it, and like many of you who
have gone through this experience, you know how painful it is
when you reach the point where a loved one no longer knows your
name.
Nearly 5.8 million Americans are living with this disease,
including 140,000 here in Arizona. Your State has the fastest
growth rate in the Country for Alzheimer's diagnoses, with the
prevalence expected to grow by 43 percent in the next 6 years.
In addition to the human suffering it causes, Alzheimer's
is our Nation's most expensive disease. It costs an astonishing
$290 billion a year, including $195 billion in costs to the
Medicare and Medicaid programs. If we continue along this
trajectory, Alzheimer's is projected to claim the minds of
nearly 14 million seniors and surpass $1 trillion in annual
costs by the year 2050.
It takes a tremendous toll on families too. Last year,
family caregivers provided 18.5 billion hours of care for loved
ones with dementia. It is often a 24/7 job that imposes a
tremendous toll on the caregivers. I remembered my mother
taking care of my father for 8 years at home prior to his going
into the veterans home in our hometown of Caribou for the last
6 months of his life, and keep in mind, my mother is now 92.
This was just last year when my father died. Even with help
from my two younger brothers and their wives, she was the one
who was there day in and day out, and I saw the toll that it
took on her.
With the increased Federal investments and public-private
partnerships, we are beginning to make progress. Last year,
Senator McSally and I worked to secure the largest funding
increase for Alzheimer's research in history, bringing us----
The Chairman. [continuing]. bringing us to $2.34 billion,
and we have worked together again this year to increase that
number still more. That is going to make the difference.
Through advances in our understanding of the brain and
imaging technologies, scientists, physicians, and
pharmaceutical companies are able to conduct clinical trials
that never would have been possible even just a few years ago.
This investment will produce progress, and I am looking forward
to learning about the new research being conducted in your
State today.
Again, I am just delighted to be here with Senator McSally
and all of you who care so much and share our passion for
combating this devastating disease.
It now gives me great pleasure to officially turn over the
gavel to my colleague, Senator McSally.
OPENING STATEMENT OF SENATOR MARTHA McSALLY
Senator McSally. Thank you. Well, first, I really want to
thank Senator Collins for holding this hearing today in sunny
Arizona. We had some travel challenges last night. We arrived
early this morning, East Coast Time, but it is really great
that we were able to bring Washington, DC, to Arizona to talk
about this really important issue, and your leadership on the
Aging Committee, Susan, has just been extraordinary. It has
just been amazing to be a part of this Committee and this
effort and to partner with you on these important issues, and
so welcome to the Grand Canyon State. We are glad to have you
back.
I also want to say thanks to the Granite Reef Senior Center
for hosting us today. This is a great venue, and thanks to
everybody who has come out to listen to this important topic,
and Mayor Lane from Scottsdale, thanks for also attending.
This just shows the example of how this community in
Arizona and across really Arizona cares about these issues, is
here to learn and identify the important things that we can do
moving forward, and what is actually happening here in Arizona
in this important space.
Today's hearing will provide an opportunity for us to hear
testimony on Alzheimer's and other cognitive diseases which
affect many aging Americans and their caregivers here in
Arizona.
Today is also the first day of November. As many of our
friends and partners in the Alzheimer's community know, the
month of November is Alzheimer's Awareness Month. When
President Ronald Reagan, who himself was diagnosed with
Alzheimer's after leaving office, first made that designation
in 1983, there were less than 2 million people with the
disease. Sadly, that number has grown threefold since that
time.
In Alzheimer's, we have the fastest-growing rate of
Alzheimer's disease in the U.S. Of the nearly 6 million
estimated Americans aged 65 and older affected, 140,000 live
here in our home State.
Furthermore, the death rate in Arizona is almost 20 percent
higher than the U.S. average. We all know someone who has
suffered from cognitive impairment, and the impact is
immeasurable.
One of my uncles suffered for many years before passing
from Alzheimer's Disease, and I have a dear friend named T.K.
Warfield, who was also my veterinarian for all three dogs I
have had as an adult, who is currently suffering from what his
doctor now thinks is Lewy body dementia with Parkinson's-like
symptoms. He had to stop caring for animals, which was his life
passion, and has been through a challenging path to find a
diagnosis and the best treatment. I have been heartbroken but
inspired by how he and his wife, Donna, are enduring the fight
against this awful disease.
I have been a strong advocate, as Senator Collins, for us
really investing at the Federal level to address these issues
and look for groundbreaking research. During my 5 years so far
that I have been in Washington, DC, I have supported year-over-
year increases in NIH funding, and we have seen an
approximately 371 percent increase in those years. That is
pretty amazing. That is overall NIH funding.
This year, we joined together, as Senator Collins
mentioned, in requesting full and robust funding for the Fiscal
Year 2020 Alzheimer's research through NIH. The funding has
made an impact in our home State, as seen through University of
Arizona's impressive research. I have and will continue to
strongly support this much needed research.
It is fantastic to see Arizona leading the way in putting
these dollars to use in Alzheimer's and other cognitive disease
research. Between our public universities, community programs,
local organizations, we are paving a path forward in fighting
against these diseases.
Today we have three amazing witnesses in order to share
their perspectives and their stories on this topic. We have got
Dr. Roberta Brinton who is the director of the University of
Arizona Center for Innovation in Brain Science, and Dr. Brinton
will discuss the groundbreaking research they have been
conducting as well as the impact of the Federal funding has had
work.
We also welcome Dr. Alireza Atri--did I say that right?
Okay.--who is the director of the Banner Sun Health Research
Institute. This institute specializes in debilitating age-
related diseases, and has had a significant impact on
generating groundbreaking research.
Along with caring for his father for 10 years, his vital
research in this field has led to potential, preventative
treatments for Alzheimer's as well best practices and
guidelines for aging adults. We welcome you and look forward to
both your testimonies.
Despite many of these advances, however, we still have a
long road to go. Today I hope not only to hear about the
successes we have achieved but also the challenges that we
still have to fight Alzheimer's and these cognitive diseases.
In 2017, in Arizona alone, there were over 300,000
caregivers--300,000 of our fellow Arizonans, who were
caregivers providing more than 376 million hours of unpaid care
to those affected by Alzheimer's and other cognitive
impairments, and it is usually a family member, like yours,
like your mom. These unsung heroes sacrifice so much to care
for their loved ones, and most of that time and effort goes
unrewarded. They often quietly forgo their careers, and the
consuming demands of caregiving can strain other relationships
and roles such as spouse or parent in addition to their own
physical and mental health.
Just last week, I met with a 26-year-old son who selflessly
moved back home to care full-time for his mother, who has been
suffering from Alzheimer's now for 5 years. This young
gentleman took what was a horrific diagnosis and actually
created what is now a virtual reality company, which allows
both cognitive and physical exercise for seniors. It is
caregivers like him that allow those with these diseases to
carry on as normally as possible.
I am pleased to welcome one of those caregivers today, Lisa
Capp. Lisa cared for her mother for 18 years, sacrificing her
time for her family. I have been moved by your story, Lisa, and
I hope you can further shed light on the impact being a
caregiver can have on an individual and a family.
Thank you all for being here, and again, thanks, Senator
Collins, for joining us today and a big thanks to our witness
panel who has given your time and your expertise to share your
knowledge and with that, I will turn it over to Dr. Atri.
STATEMENT OF ALIREZA ATRI, MD, Ph.D,
DIRECTOR, BANNER SUN HEALTH RESEARCH
INSTITUTE, SUN CITY, ARIZONA
Dr. Atri. Good morning, Chairman Collins, Senator McSally.
Thank you very much for providing me this opportunity to
present a brief perspective of our understandings, challenges,
and projected impact of Alzheimer's Disease and Related
Dementias, ADRD.
I am a cognitive neurologist. I am a neuroscientist, and as
you know, I also took care of my father at home for over 10
years. Before that, when I was 19, it was my aunt, who was like
a mother to me, so this has a really personal perspective. I
also take care of patients and families with early onset
disease, so my patients in their 40's and 50's.
As you know, Alzheimer's disease is the most common cause
of cognitive impairment in individuals over 65, and we have a
pandemic in the world because of longevity, and it is the sixth
leading cause in the United States and is the only one in the
top 10 that is really significantly increasing.
Alzheimer's Disease and Related Dementias are brain
diseases. They are not a normal part of aging, and that is
really important because recently there was a survey with ADI
that showed that still 60 percent of individuals around the
world, including clinicians, still think of this as a normal
part of aging, which it is not.
These diseases insidiously cause brain damage that over
decades leads to, at first, subtle impairments in cognition and
behavior and later to dementia, which is a gradual decline and
ultimate loss of independence. They slowly ravage the brain by
depositing toxic clumps, we understand now, of proteins. First,
these proteins pollute the brain, and then there is basically--
they light a fire that spreads in the brain, and this causes
damage to the brain's infrastructure through inflammation,
through vascular damage, and disruption of cell energy
mechanisms, connections, structures, and networks, and
ultimately leads to neurodegeneration, which is cell death.
The signature of Alzheimer's disease changes is now
measurable during life using things we call ``biomarkers,'' and
so we can actually measure these toxic proteins in a spinal
fluid through spinal taps, which is very common in Europe, but
we do it less here, and also through novel brain scans that are
expensive but possible to do.
Soon, what is really exciting, we will be to measure these
through blood, and this is going to really revolutionize our
understanding and also accelerate the basic research.
We think that, actually, probably with about 85 to 90
percent accuracy, these tests will be able to find these
proteins and also give us suggestions about cellular damage,
which is also important, and these are going to lead to
personalized diagnoses and therapies, which we really, really
need, because it is not just one disease actually. It is a
number of things that come together that cause brain damage and
therapies to prevent, retard, and even potentially reverse the
damage and clinical symptoms and allow us to intervene earlier
before there is widespread damage, which is really, really
important.
As you know, if an intervention that could start delaying
by 5 years Alzheimer's disease and ADRD dementia phase, if we
had the therapy by 2025, this would reduce about 50 percent of
Medicare costs by 2030, and by 2030 to 2035, it will spare
about 2.5 million to 4 million Americans with a dementia phase.
We also continue to face challenges in the clinical
setting, unfortunately, because of timely diagnosis detection,
accurate disclosure, management, and care. Too often, cognitive
and behavioral symptoms go undiagnosed or are misattributed.
This is despite decades of advances regarding criteria and
imaging and knowing the meaningful benefits of timely diagnosis
for the patients and caregivers.
Most individuals are not diagnosed until the moderate
stages of dementia, and up to 40 to 50 percent of individuals
with dementia never actually get a full accurate diagnosis or
disclosure. This is regrettable, and the barriers to this are
actually mitigatable, I think.
One of the barriers, I think, is of knowledge and
guidelines. We do not actually have national best practice
guidelines for evaluation, diagnosis, and disclosure of
Alzheimer's disease. I serve as co-chair of the U.S.
Alzheimer's Association Work Group for this, and so we will
have this report being finalized and available to the public
and the medical field in early 2020.
You went very eloquently over the staggering costs, both in
terms of money and people. Every State is going to have an
increase over the next decade, 12 percent at least in every
State, and in Arizona, up to 43 percent, and that 18.5 billion
hours of informal, unpaid caregiving, basically a low-estimate
cost of that is $234 billion that was spent but not counted in
the economy.
It turns out the socioeconomic costs of ADRD really,
typically began years before the diagnosis, and we have done
some research that is international research to show that the
cost, calculated across studies, really support that we are
really failing to estimate the cost properly.
For example, out-of-pocket costs for people with dementia
are up to a third of their household wealth in the final 5
years of their life, and caregivers have health care costs
themselves that are twice as high as non-caregivers. We also
found evidence that these costs are actually rising, up to 10
years before, lower savings, less employment, and all this is
paid for by somebody. Employers are paying for it, and we are
paying for it.
These are the costs, but this actually says that we have
opportunities to mitigate this. The opportunities are going to
come through technologies: possibly diagnosing and caring for
people in a timely manner earlier; using real-time data and big
data, for example, integrating health records with insurance
data bases; gathering real evidence from longitudinal cohorts
in the clinic, for example, and seeing how these costs are
spread through the whole system; and capturing basically which
stakeholder pays for what and when; developing resource
utilization models that support the rational allocation and
investment decisions; and to have better value recognition of
illness frameworks that consider both the direct cost when
money changes hands and also the indirect cost of this
caregiving and then the hidden cost of quality of life and how
it affects the economy. These need to be measured better.
This is a bipartisan effort, and we really appreciate the
fact that the funding has gone up tremendously over the last 5
years, and this is actually paying dividends already in this
sense.
The State of Arizona actually has been very forward-
thinking in this way. The last 20 years, there is an Arizona
Alzheimer's Consortium that has funded a lot of research, both
at Banner and sister institutions, to actually have seed money
that gets funded and matched with other things, and this has
actually led to a number of big projects, including projects in
Alzheimer's prevention that happen not just here but globally
around the world, recruiting lovely people to the State. I have
only been here for over a year, and you have been here for 3
years, so it is really helping with that and actually pushing
care out in biomarkers. Biomarker development, we want the
epicenters here.
It is a very interesting time in our field, and we now
appreciate the damage that is starting silently, 15 to 20
years. Ultimately, we have that period that we can intervene.
We also appreciate that when people get in their 80's, they
just do not have Alzheimer's changes. They have vascular
changes. They have inflammatory changes. Maybe viruses and
bacteria may be involved to trigger things, so those are all
important. We still need multipronged approaches, not just one
approach to do this.
In the last 2 years, it has been the best of times and the
worst of times for us. We have had a lot of disappointments,
but we have learned from those. From those setbacks, one of the
major things we have learned is that we need biomarkers, better
biomarkers to allow us to measure things and know where we are
going.
Finally, we can actually have some therapies that are
removing the amyloid protein from the brain, and we have shown
this now, so the question is if you remove the amyloid, are we
going to change clinical course? And there is some suggestion
to that, and we need to go earlier.
We have also learned that we need to diversify our
portfolio, that you will hear more about that, not to just look
at amyloid, but also look at tau and inflammation and all kinds
of other mechanisms and targets and interventions---and also
always promoting basically lifestyles, such as exercise, proper
nutrition, mitigating super-vascular risk factors, and engaging
in cognitive and social activities. If we do this early enough,
there is actually a fair bit of evidence that about 30 to 35
cases of dementia worldwide are actually preventable because
people will not manifest the symptoms. Their brain will be much
more protected.
We are in a really critical period that requires strategic
planning and investment and collaboration. This is, as you
know, not a ``them'' problem. It is an ``us'' problem. It is
too big for one sector to solve by itself, and we need
collaboration and continued support, and I am confident with
continued bipartisan support and leadership that we will rise
to the challenge because we have to do it. We have to provide
better care now for families and patients who really depend on
us and to prevent and cure Alzheimer's disease and ADRD not
just for our generation but also for the next generation.
Thank you very much.
Senator McSally. Wonderful. Thank you, Dr. Atri.
Dr. Brinton?
STATEMENT OF ROBERTA DIAZ BRINTON, Ph.D,
DIRECTOR, CENTER FOR INNOVATION IN BRAIN SCIENCE,
UNIVERSITY OF ARIZONA, TUCSON, ARIZONA
Dr. Brinton. Good morning, Senator Collins, Senator
McSally. Thank you for the opportunity to address you on the
Arizona Perspective on Aging: Alzheimer's and Other Cognitive
Diseases. I am Dr. Roberta Diaz Brinton, the director of the
Center for Innovation in Brain Science at the University of
Arizona. Our mission is to create innovations in brain science
of the future for those who need a cure today.
We are an all-brains-on-deck translational ecosystem
dedicated to addressing the urgent national health crisis of
Alzheimer's disease. I am honored to share with you the
advances being made in Arizona to prevent and cure Alzheimer's
disease.
Curing Alzheimer's disease is not rocket science. It is
harder. That is the bad news, but I am here to deliver the good
news.
Arizonans have a bold pioneering spirit, as Senator McSally
knows, and an innovative culture that is exemplified through
the Center for Innovation in Brain Science. Across the State,
researchers and clinicians are working together to prevent,
delay, and cure Alzheimer' Disease through the Arizona
Alzheimer's Consortium, as Dr. Atri mentioned.
The University of Arizona's Center for Innovation in Brain
Science was created to address the challenge that in the 21st
century there is not a single cure for a single
neurodegenerative disease.
We operate as a university-biotech hybrid focused on age-
associated neurodegenerative diseases, and it is unique in the
Nation and likely the world. CIBS is a mission-driven all-
brains-on-deck translational ecosystem that integrates the
discovery prowess of academia with the best practices of
biotech.
Our pipeline of innovative therapeutics for Alzheimer's
disease include regenerative therapeutics that activate neural
stem cells in the brain, promote energy production in the
brain, reduce neuroinflammation, and prevent generation of
Alzheimer's pathology.
A prime example of the success of our efforts and yours,
after decades of painstaking research supported by National
Institute on Aging, we are prime to conduct a Phase 2 clinical
trial of allopregnanolone as the first regenerative therapeutic
to regenerate the degenerated Alzheimer's brain. That is bold,
and that is Arizona.
The National Alzheimer's Project Act is an ambitious plan,
as you know, to prevent and effectively treat Alzheimer's
disease in 5 years. Through the transformative and innovation
leadership team at the National Institute on Aging, we are
closer than ever to delivering on these goals. Federal
investments have resulted in discovery of mechanisms and
drivers of Alzheimer's and a broad portfolio of therapeutics
currently in clinical trial. We now know one-size therapeutic
will not fit all and will not fit all for all time. We will
require a broad portfolio of therapeutic options that address
both sex biology, Alzheimer's biology, and the progression of
the disease.
To deliver prevention and treatment of Alzheimer's by 2025,
two advances are critical. As Dr. Atri mentioned, we need big
data analytics for precision prevention.
Electronic medical records held by the Federal Government
hold the key to detecting and preventing Alzheimer's disease in
at-risk populations. For example, using existing NIH-funded
clinical trial data, we were able to identify women at
increased risk of Alzheimer's disease while they were still
healthy, and this provides the opportunity to intervene in this
at-risk population when they are still healthy with FDA-
approved therapeutics to reverse the trajectory of risk.
Using Medicare data, we demonstrated that specific statins
reduced the risk of Alzheimer's disease in an ethnically
diverse national population. Using insurance claims data, we
were able to demonstrate that specific breast cancer therapies
can reduce the risk of developing Alzheimer's disease in women
later in life. We are currently conducting a comparable
analysis of prostate cancer therapies and the risk of
developing Alzheimer's in men.
We are now partnering with researchers at the Veterans
Administration to determine which therapies for type 2 diabetes
reduce or increase the risk of developing Alzheimer's. Through
big data analytics, we can inform clinical care to prevent
Alzheimer's disease in at-risk populations.
Our veterans face a unique constellation of risk-factors
for Alzheimer's, including high stress, sleep deprivation,
toxin exposure, and traumatic brain injury.
The challenges associated with accessing and analyzing
veteran health records puts this group at risk when we could
prevent Alzheimer's. Through their medical records, our heroic
veterans on the battlefield can be heroes again in the fight
against Alzheimer's.
I urge you to find a way to safely, securely, and
efficiently expand access to electronic medical records held by
the Federal Government and mandate the sharing of HIPAA-
compliant patient-level data from federally funded clinical
trials.
Precision medicine cures for Alzheimer's requires Arizona
commercialization innovation. Big pharma and venture capital
are abandoning Alzheimer's and other age-associated
neurodegenerative diseases. However, their departure is
Arizona's opportunity to become the new biotech hub for curing
Alzheimer's.
A challenge to delivering our discoveries to patients is
that commercialization of federally funded therapeutic
development ultimately reaches a valley of death. Critical to
delivering precision medicine cures for Alzheimer's is an
accessible network of innovation experts to advance
intellectual property opportunities, startup capital, business
development, and the commitment to find a way to--yes, to
achieve the goal for the American public.
The National Institutes of Health, SBIR, STTR, and
Commercialization Accelerator Program are engines of
commercialization that, with modest adjustments, could catapult
therapeutic development across the valley of death.
The war against Alzheimer's Disease is being fought, as you
said, already on many fronts, from the homes of patients and
caregivers to the research laboratories of scientists and
clinicians across this great Nation. Millions of Americans are
counting on us to win this fight. We can, we will, we must win.
Arizona, with its bold pioneering spirit and
entrepreneurial culture has a unique opportunity to lead the
Nation and the world in the science of aging and innovative
therapeutic development for Alzheimer's and age-associated
neurodegenerative disease. Arizona can deliver precision
medicine of the future for those who need a cure today.
Thank you for your commitment to our Nation and to Arizona,
and for your efforts, we are closer to curing Alzheimer's.
Thank you.
Senator McSally. Thank you, Dr. Brinton. I really
appreciate it.
Ms. Capp?
STATEMENT OF LISA CAPP, PREVIOUS ALZHEIMER'S
DISEASE CAREGIVER, PHOENIX, ARIZONA
Ms. Capp. Senator McSally, Senator Collins, and
distinguished guests, thank you for the opportunity to testify
about my experience as my mother's caregiver.
I am a blogger, an activist, and a dementia caregiving
survivor after an 18-year journey through the disease with my
mother, Vera Cappelletti. After her death in 2015, chairing the
Board of the Vermont Alzheimer's Association and a recent move
to Phoenix, I am now co-chairing the board of the Desert
Southwest Alzheimer's Association Board. I write and speak
regularly on the subject of dementia caregiving.
Why is that important? In 2014, comedian Seth Rogen
addressed lawmakers in congressional testimony about the care
of his wife's mother who was diagnosed with young-onset
Alzheimer's. She was in her mid-50's. Back in 2014, Seth said,
``I think until you see Alzheimer's firsthand, it is kind of
hard to conceive how brutal it really is.''
Today dementia caregiving remains equally brutal around a
still-stigmatized disease driving family caregivers deeper into
emotional, physical, and financial hardship.
Mom came to live with us after my dad passed away, and at
the time, I was advancing my career in high tech. I was lucky.
My husband, Tom, who is here with me today, shared fully in my
role as caregiver, and without children due to my infertility,
we did not count ourselves among those in the sandwich
generation of care, as so many are.
My mother's dementia began with whimsical imaginings but
turned to terrifying delusions and hallucinations. Tom and I
continued care in our home until crisis, crisis that left us
with no choice but to involuntarily commit my mom to a
psychiatric ward in order to stabilize her condition.
My siblings, although living in other parts of the Country,
participated in many ways, but most notably in our family's
decision to move my mom not back to home from the hospital, but
instead to live the remainder of her life in full-time memory
care.
As my mom slid deeper into her dementia, the invisible
battle became a struggle I had to watch progress while plaques
and tangles took over her brain.
We were blessed by a relationship with a skilled geriatric
psychiatrist who helped me to understand my mother's world just
a little bit better.
Dr. Paul Newhouse asked, ``Do you know what deja vu is,
Lisa?'' ``Feeling you have been somewhere before, like it is
familiar,'' I answered.
He said, ``Yes. Deja vu means that the strange is familiar
to you, but do you know what jamais vu is?'' and I shook my
head no. ``Jamais vu is what our friends and family can
experience in dementia. The familiar becomes strange. Imagine
every moment of your life struggling with something you know
and you have known your entire life, but now it is strange to
you,'' the doctor shared with me.
My life was busy. I did not understand the nuances of my
mom's brain disease. With the stress of having to leave work
early to get mom to one of her many doctor appointments, she
might pick up a comb and look at it as if she had never seen it
before, confounded by its very function. I would grab the comb
from her hand and smooth her hair as we rushed out the door
late for our appointment, but waves of guilt kept building in
me. The emotional web between someone you love living with
dementia and you as the unexpected caregiver are made up of
strands spun from loss, despair, sadness and intense feelings
of inadequacy.
I think about the arc of my mother's life from wife,
mother, and career; through the hallucinations and delusions;
and on to the advanced stages of dementia. Bedridden with her
ability to speak gone, I would lay my iPhone on her pillow and
play Frank Sinatra singing ``Fly Me to the Moon.'' Her
beautiful green eyes would open, and light would dance in them
but from a deep and far-away place.
Dementia is a set of perpetually evolving diseases
requiring the act of caregiving to be both collaborative and
yet co-dependent. As someone living with dementia progresses,
so does the caregiver along the paths of physical, spiritual,
and emotional coping. As one individual declines, the other
must advance and the end of caregiving is not rewarded with a
sense of freedom. It is marked instead by deep and intense
grief at yet another loss to this despicable disease.
I am hopeful, more hopeful than I have ever been, that I
will see the first survivor of this disease in my lifetime. The
unprecedented funding you and your fellow legislators support
is leading not only to critically important research
discoveries like you have heard today, but to a renewed hope
among caregivers for earlier detection, prevention, and an
ultimate cure.
I thank you. I thank you, Senator Collins, for your
leadership as Chair of the Senate Special Committee on Aging
and for your support to programs, policies, and funding,
critically important to the Alzheimer's Association and those
in our Nation requiring their services.
I thank you, Senator McSally, for your support to the
younger onset bill, H.R. 1903, which passed the House this
week. The bill will give access to critical resources for those
living with dementia under the age of 60 as part of the Older
Americans Act, services they do not have access to today, and I
welcome the opportunity to work with you, Senator McSally, on
initiatives that continue to benefit our great State and the
Nation.
There are still so many opportunities yet to exploit. We
need to educate and train primary care physicians, first
responders, ER and hospital staff, caregivers and
administrators in local care facilities, major employers and
small business owners for whom caregivers currently work,
barbers, lawyers and bankers, all who see the impact of this
disease in their day-to-day lives and in their day-to-day work.
I applaud Mayor Mitchell and the city of Tempe for their
work in becoming a dementia friendly city and to Mayor Gallego
for considering similar steps in Phoenix. T These actions
enabled by your support to The Hope Act, H.R. 1873, go a long
way in removing stigma around this disease and in making life a
bit easier for caregivers.
I will end my comments by sharing although my legal name is
Lisa Beilstein, I write and am active as Lisa B. Capp in my
mom's memory.
Thank you for giving me the opportunity to speak, for
listening to my story, and for all you have done and will do in
the fight we share together to ultimately live in a world
without dementia and Alzheimer's disease.
Senator McSally. Wonderful. Thank you, Ms. Capp, for
sharing your story in such a personal manner and your continued
advocacy for caregivers and for victims of these diseases.
There is so much to talk here. I mean, we were taking
copious notes.
I want to first start with--I opened up with this statistic
that 20 percent more deaths are happening in Arizona than in
other parts of the country from Alzheimer's disease.
Dr. Atria or Dr. Brinton, do you have any sense of why that
is such a higher significant percentage?
Dr. Atri. I am not sure, but I think we probably have older
individuals here with multifactorial disease, and so, in some
ways, they may have some comorbidities that are made worse by
dementia and that is one of the things that is interesting is
that I think with Alzheimer's disease, it is still
underreported, even though it is a sixth leading cause. When
somebody dies in the end stages, they may say it is their heart
or their lungs or their infection, but really it is the
Alzheimer's disease that got them to that point where they
could not swallow well and they got the pneumonia, et cetera.
Senator McSally. Okay, great.
Dr. Brinton, do you have anything to add?
Dr. Brinton. I do not have expertise in this area.
Senator McSally. Okay.
Dr. Brinton. One of the things that concerns me from my
experience of conducting clinical trials is that women, who are
disproportionately affected by Alzheimer's disease oftentimes
do not have the caregiving network that a man might have. If
there is no daughter in the family or there is no daughter-in-
law in the family, that actually poses a fairly large challenge
for women with Alzheimer's disease. They can experience dealing
with the disease largely on their own, so that would be a
concern that I would look into about why that might be.
Senator McSally. Well, I want to followup on that, Dr.
Brinton. We were talking in the back about how the gender split
of how Alzheimer's is so disproportionately impacting women
than men, and you went through the other cognitive diseases and
how that has got significant gender differences. Can you just
share a little bit about the research and understanding related
to specifically how these types of diseases are impacting men
and women so differently?
Dr. Brinton. Yes. To begin with, there has been an
assumption in the Alzheimer's field that there are more women
living with Alzheimer's than men because women live, on
average, 4.5 years longer than men, but we all know that the
disease is 10 to 20 years in the making. Average age of
diagnosis of the disease is in their 70's. Well, it does not
take a rocket scientist to do that simple math of 70-ish minus
20-ish, and you run into 50-ish, which is the average age of
menopause and that endocrine aging transition actually can
unmask the risk of developing Alzheimer's disease in women.
We are already able to detect beta-amyloid plaque in the
brain of some women and particularly those women that carry the
risk factor for Alzheimer's disease, the APOE-e4 gene, and one
of the exciting outcomes of an earlier study that we did was
that those women who were at risk and still healthy but were
developing significant cognitive decline were women who had
dysfunction in their metabolic system. They were still within
normal range, but they were on the wrong end of normal and it
turns out they carried the APOE-e4 gene.
The APOE-e4 gene is not an absolute risk factor because
what was really interesting is that in this entire study in 500
women, there was an equal distribution of the Alzheimer's risk
factor APOE-e4. It only occurred that the cognitive decline
only occurred in women who were postmenopausal. They were all
postmenopausal, and they had metabolic dysregulation, and they
were APOE-e4-positive, so you cannot change being chromosomally
female. You cannot change your age, and you cannot change being
menopausal but you can change your metabolic health because we
had APOE-e4 women in the metabolic healthy group of women who
showed who actually had fantastic cognitive function, so,
again, early intervention.
At the time and I think part of what we really need to
focus on is how can we deploy this scientific knowledge into
the clinical space. I think we still have those hurdles to
overcome that we can discover, and then how do we actually
reach the clinician? How do we do that effectively?
I speak to many physician groups, but there has got to be
this way that we communicate more effectively to the clinical
world.
Senator McSally. Just to followup, when you say metabolic
function, can you put that in layman's terms?
Dr. Brinton. Yes. It is really around glucose metabolism,
and we know that type 2 diabetes is a risk for developing
Alzheimer's disease and the reason for that is the brain
consumes 20 percent of the glucose--20 percent of the glucose,
20 percent of the oxygen. It is 2 percent of the body weight
and consumes--it punches above its weight, so from here down,
we are a Prius. From here up, we are a Hummer, so the brain
is----
Senator McSally. I asked for layman's terms. Everybody can
picture that.
Dr. Brinton. Yes. The brain is an energy hog, and so when
you look at type 2 diabetes, we typically think about type 2
diabetes as really from the neck down but the first organ
affected is the one most dependent upon glucose.
Dr. Atri. Let me add to that also because I think part of
the metabolic syndrome, there is also the glucose metabolism.
There is also obesity and also inflammation.
Dr. Brinton. Yes.
Dr. Atri. Micro inflammation.
Senator McSally. Okay.
Dr. Atri. That is huge. Things that are inflammatory to us
are bad for the brain and bad for the vessels.
These interactions between glucose and insulin, they
actually work in the Alzheimer's pathways----
Dr. Brinton. Yes.
Dr. Atri [continuing]. and they interact with APOE-e4.
Senator McSally. Interesting.
Okay. One quick question for Ms. Capp, and then I will hand
it over to Senator Collins.
You were with your mom when she was first diagnosed, right,
through her whole journey? I mean not with her, but you have
seen that whole journey that she has been through. Can you
share some perspectives? The early prevention and the early
indications that somebody may be prone to the disease are so
critical, and in addition to some of the legislation that you
mentioned, I am a proud cosponsor of another bill which is
called the CHANGE Act, which requires testing for cognitive
impairment or progression in both the Welcome to Medicare
initial exam and the Medicare annual wellness visits.
I know a lot of the research is trying to catch it much
earlier than that, but this seems like common sense, but can
you just share just personally how it manifested and the
journey of even trying to get a diagnosis and understand it
all?
Ms. Capp. Sure. I think the most difficult part of the
early stages of dementia, whether it is younger onset or later
onset, is the dynamics of denial.
When we are functioning at the levels, we are all
functioning at, at the peak of our lives, at the peak of our
careers, to recognize that something is wrong or for family
members to admit that something just does not seem right is
very difficult and that is why I focus on the stigma of the
disease. It is critically important for us to remove stigma. It
is a brain disease. It is no different than any other disease
in terms of acceptance in our communities and support, and that
is why dementia-friendly cities are so critically important.
Bankers often see it first before families. Family members
often hear from neighbors that your mom or your dad are just
not right. Things are not right. That part of overcoming denial
and coming to acceptance allows people to finally get into a
doctor's office to begin to try to get a diagnosis.
We did not have a diagnosis until very late because in the
years that my mom was going through this, it was even more
stigmatized.
It is critically important to be accepting, to understand,
to learn the signs of Alzheimer's and dementia, so that
everyone understands.
For those people who have not been touched by the disease--
and we talk about how many families have, but for those who
have not, the things that could be said can be very cruel. It
is just about moving on.
It took a long time for us to understand what was going on.
I am very interested in the research because my mom, although
passing away in her late 80's, has a sister who is still alive
at 101, so that Petri dish is pretty small and her sister
traveled to Italy last year by herself. The dynamics are
critically important for us to understand and for family
members to know they can deal with this and get support.
Our geriatric psychiatrist was enormously successful. I
will say there are far too few geriatric psychiatrists, and
there are far too few primary care physicians who know how to
detect and help family caregivers come to acceptance and out of
denial.
Senator McSally. Great. Thank you.
Senator Collins?
The Chairman. Dr. Atri, I am going to take up where Ms.
Capp just left off, and that is you had a startling statistic
in your testimony about the number of clinicians who will not
recognize the early signs of Alzheimer's. I think perhaps that
is what you were going to comment on.
Dr. Atri. Exactly.
The Chairman. Go right ahead.
Dr. Atri. That is exactly right. Part of it is stigma, but
part of it, again, is that lack of knowledge and resources. It
is remarkable that people get touched by all kinds of
clinicians, and yet these things go under the radar.
Years before there is a cognitive issue, it is actually
unscrupulous telemarketers and other folks to recognize things.
It is not just memory. It could be judgments. These things
start manifesting themselves years before.
Sleep issues, anxiety, what appears to be like depression
but is really a lack of motivation and withdrawal. We become
very, very good as clinicians recognizing those things, but
when we think of those things, those are just brain chemicals
changing, oftentimes because of neurodegeneration.
If you look at older adults who have those changes and you
look forward, it turns out that many of them have
neurodegenerative processes, and there is evidence to show that
actually if you treat some of those earlier, you can actually
change and ward off dementia.
We do not wait for any other disease to say, ``You know
what? Let us wait for the cancer to metastasize until we treat
it'' or ``Let us make sure you have compression fractures
everywhere before we do something about it.'' Or if you go to
see somebody and you say you have chest pain, they do not say,
``Oh. You are getting old. Everybody has chest pains,'' right?
Or if you are breathing a little bit heavy, ``Oh, you are just
older.'' No, you do something about it, and we have to have the
same urgency about this where people come and there is a
concern, whether it is a clinician, whether it is a family
member, or the patient themselves. We have to do something
about it because it turns out those costs that are increasing
years before, it is not because suddenly the out-of-control
diabetes changed metabolically. It is not because suddenly the
heart started pumping the wrong way. It is because people were
not managing their medications correctly. The falls, the
hospitalizations, those are incredibly costly.
The Chairman. Thank you, Doctor. I think you are exactly
right.
The most important fact that everyone needs to accept is
this is not a normal part of aging. It is an illness. It is a
disease, but I know when I was growing up, people referred to
is as senility, and it was just accepted that that is what
happened when you got old. Now we know it is a disease. It is a
disease. It is shocking to me that there is still this
reluctance to screen for, diagnose, and do whatever we can.
I want to switch to what we can do because although we are
doing a lot better in identifying risk factors and also have
improved brain research enormously, and, boy, if we could do a
blood test to identify biomarkers, that would be terrific as
well but we have made big progress in imaging of the brain to
identify Alzheimer's too, but just last night on our very long
journey to get here because of plan problems, weather problems,
I read a story in the Wall Street Journal that talked about the
work that is being done on prevention, and I will say, as
someone whose family--it is not just my father but two uncles,
my grandfather--have died from Alzheimer's disease that I
always felt there was very little that you could do if you had
a bad family history and then you had age, which is obviously a
non-controllable risk factor.
This article suggested that studies are now showing that
exercise, diet, sleep, meditation, all can play a role. What is
your opinion of that? Dr. Brinton, I want you to comment on
this as well.
Dr. Atri. The data for that is strong in a population
sense, so you are always trying to--it is like this teeter-
totter. You have some of those risk factors, your genes, et
cetera, if you have had severe head injury, all the things that
take away your reserve.
Then on the side that is giving you cognitive reserve are
things like education, cognitive attainment, exercise. I tell
my patients, ``Gosh, if I had the benefit of that pill to give
you growth factors in the brain and increase blood flow and get
this garbage out of your brain, I would do it, but I do not
have that pill. It is called exercise.'' What is exercise? It
is what you will do.
Isolation, depression, these metabolic risk factors, they
have all been shown in a population sense to put on the balance
sheet, the part that gives you more reserve, and so those are
the things we can do.
The Chairman. I think that is really encouraging. I must
say I am really surprised but heartened by that, because it has
felt so uncontrollable, and the clinical trials, many of them
have been so disappointing in recent years.
Dr. Brinton, I would like you to comment on prevention
also, but before you do, I want to tell you that when we were
talking earlier and then your testimony that you also dispelled
a myth that despite my 20 years of examining this issue, I
held, and that is I thought the reason more women were affected
is women lived longer. Whereas, you are suggesting there are
different biological reasons that make women more prone to it,
so if you could expand a little bit on that as well as the
issue of prevention.
Ms. Brinton. With regard to the sex differences that
Senator McSally brought up earlier and is relevant to your
question is there a preponderance of women who develop
Alzheimer's and multiple sclerosis. Those two disease are more
prevalent in women, and men have greater prevalence of
Parkinson's and ALS. It is not all or none. It is about a 60-40
split, except for ALS, where it is more like a 70-30 split.
We begin to look at, well, what drives that? Well, we are
different. I know. Women have a lipid biology. We are tasked
with reproducing the species and feeding it a high-lipid diet
called breast milk, so our biology on the whole is a lipid
biology.
Then we look at the diseases that are more prevalent in
women. They turn out to be diseases of lipid dysregulation and
inflammation that targets lipids.
For example, what we see early on in the course in both our
discovery science and now in our clinical science is that women
can experience following the menopause and the loss of estrogen
in the brain, a decline in white matter. The white matter is
the lipid of the brain, and it constitutes 60 percent of the
brain weight, so what happens is--what we think is happening is
that the brain is sending out a starvation signal, ``I am
starving,'' because estrogen regulates, promotes glucose
utilization in the brain. Now there is a loss of estrogen, and
the brain sends out this starvation signal, ``I am starving.
Send me fuel.'' Well, the starvation response is actually to
metabolize lipids into a fuel that the brain can use as an
auxiliary backup, which is bodies, so far, so good, except for
the fact that 60 percent of the brain is lipid, and now what we
see is that the white matter in the brain can actually be a
source of those ketone bodies to fuel the energy demand of the
brain.
Not a good-news story. However, there is a substantial body
of evidence that indicates that in women with symptoms of the
menopausal transition that estrogen therapy at the time of the
symptoms, not 10, 15, 20 years later, but at the time of the
symptoms can actually reduce the risk of developing Alzheimer's
disease.
Again, I come back to kind of the nuances of therapeutic
development and therapeutic intervention. Timing matters. One
of the things that we did is we understood that women were
voting with their feet. There were a lot of reports about the
adverse effects of hormone therapy. Women stopped using it for
the fear of breast cancer, largely.
We developed an alternative to estrogen therapy that is
safe and effective in brain and works like an estrogen in brain
but not as an estrogen in the breast or the uterus, so these
are aware--and now I come back to this commercialization
hurdle. We have that. Now we have to commercialize it and walk
through that valley of death looking for commercial partners to
actually bring this to--and we have done a clinical trial on
this.
Now, you do not need a business opportunity to exercise,
although people have made a substantial amount of money on
exercise business but what I would say is that I think we can
do a better job of communicating about what exercise is. You do
not have to go to the gym to exercise.
I exercise pretty much every morning when I race from my
house and I walk that aerobic 10, 15 minutes to my office,
because I am always racing, as my team will tell you, and then,
but wait a minute, I could take some steps and then, oh, I have
an elliptical at my desk at work and my desk at home, and I
stand at my desk, and I rarely sit during the day. This is the
longest I sit, typically.
I think we can, from a clinical perspective, build in that.
Exercise does not mean going to a gym. It means get out there
and walk, and walk fast. Carry those bags. Do not carry them in
the grocery cart. Get yourself some exercise, so there are a
lot of ways that we can execute exercise without having to take
that out of our day.
Last what I would say, again, coming back to the
opportunities for therapeutic development, there is a rich
pipeline. There is a rich pipeline. It is a very exciting time.
Although there have been 100-plus failures, behind that is 30
years of steadfast work that has been funded by the Federal
Government, in large measure, that is coming forward, that
because of your funding, because of your financial commitment,
the doors are open. Our clinical trial of the first
regenerative therapeutic for Alzheimer's disease would not be
possible without that funding. It is tool bold. It is too out
of the box, and yet in our Phase 1b/2a clinical trial, people
said you will never see anything but they did not think about
that the brain can actually regenerate.
We have encouraging data, not final data, but encouraging
data that the Alzheimer's brain is fighting the good fight. It
is trying to survive, and that we can actually rebuild that
brain and that life.
The Chairman. Very interesting.
Ms. Capp, what advice would you give to other caregivers
based on your experience?
Ms. Capp. I spend a lot of time talking to current
caregivers because when you enter that tunnel, it is pretty
dark, and often there is not a lot of information.
One of the things I would say on this discussion of
prevention is it is critically important for caregivers to
focus on these prevention messages as well.
Isolation. Caregiving is a very isolating experience.
Caregivers have to get help, and asking for help is a very
difficult thing for most caregivers to do.
Exercise. Caregivers are so focused on the tasks of
caregiving. They have no time even to take a walk.
One of the things that we are seeing a lot of interest in
and energy around are programs. Actually, there is a comedian--
I cannot think of his name--from ``Will and Grace,'' the show
``Will and Grace,'' who is Seth. It escapes me. He has been
joining up, as many celebrities have, in this program called
TimeOut, and what it provides is data gathering about what
caregivers need, so if a caregiver cannot speak their need for
time or support from family or friends, they can go into a data
bank and they can ask for it. People can commit time to support
them because even a little bit of time away from caregiving is
going to help caregivers.
Caregivers are giving up opportunity to go to the doctor,
to take meds, to do so many things to support their own health,
so that is what we focus on is self-health.
The Chairman. Thank you.
Ms. Brinton. I wanted to quickly just make mention that we
have developed an app. Alzheimer's is personal, and assessment
should be too. We developed an app that assesses what is
important to that person with Alzheimer's and what is important
to the caregiver, so the caregiver gets the app, and the person
with Alzheimer's gets the app.
What we are doing is being very mindful that, first of all,
maybe what we are measuring in a standardized way in the clinic
actually is not detecting, and what we learned from the
caregivers is that there is a lot that is being changed during
a clinical trial that is not detected on the standardized kind
of assessments.
The other is that we want to make sure that the caregiver
is not the next Alzheimer's patient.
The Chairman. Thank you.
Senator McSally. Well, exactly. Actually, I wanted to pick
up on that because, as I am thinking about this, we now have
women who are more susceptible to be Alzheimer's victims. We
have women who are more likely to be the caregivers, which
includes being out of the workforce, and the additional stress
on them and their lifestyle and their physical and their mental
health, which also includes financial instability. They are
living longer, but then they will have less paid into Social
Security and less paid into any other retirement system, which
then makes the cycle of them being more susceptible just
biologically but then for other conditions to be the next
victim. This can be a generational issue that is
disproportionately impacting women in a very profound way.
How do we break that cycle? We know from the kind of light
bulb that came on for us today now that women are impacted more
biologically, so we cannot change that. Women are more
caregivers. I mean, societally wise, women taking on those
responsibilities as a group but how do we break that cycle
specifically impacting women in such a profound way?
Dr. Brinton. Well, I think, frankly, you both exemplify
that. Women leaders make a difference.
Senator McSally. Ms. Capp, anything else to share on that?
Ms. Capp. I absolutely agree. It is about building
awareness.
Senator McSally. Yes.
Ms. Capp. The one thing I am very hopeful for is although
women are the vast majority of caregivers in our generation, in
the millennial generation we are seeing that shift. It is more
split.
Senator McSally. Like the young man I mentioned in my
opening statement.
Ms. Capp. Absolutely.
Senator McSally. It is more split, you are saying?
Ms. Capp. Yes.
Senator McSally. Dr. Brinton, I wanted to go back to the
veterans issues. A veteran myself, we have about 500,000 here
in Arizona. You said we are uniquely at risk for Alzheimer's
and other cognitive diseases because of our stress, because of
our toxic exposure, and traumatic brain injury. I think those
are the three you mentioned, right?
Can you talk a little bit more about that and the
uniqueness of a veteran's risk? Then I want to know a little
bit more about the barriers you mentioned related to
information sharing with the Veterans Administration, because
we happen to be able to do something about that.
Dr. Brinton. Wonderful.
With respect to veterans, we had two wonderful ROTC
students in the center conducting research, and they were
wonderful fellows. Wonderful. Then I was shocked to hear that
in their trajectory going on from when they graduated from the
University of Arizona, that their job would require them to
stay awake for 48 hours. How do you do that? How do you do
that? That is disconcerting to someone who understands brain
function and the necessity of sleep, so those are some of the
issues.
The other is--I know from a perspective is ALS, being in
the military is actually a risk factor for ALS.
Senator McSally. Yes.
Dr. Brinton. The reason is more likely because of the
exercise demands through the military, that there is intense
exercise requirements, and that exercise does not quite capture
carrying how many pounds of weight while you are running in
battle.
There is a disproportionate number of veterans who develop
ALS, and it is, again, coming back to ``Why is that?'' Well,
our hypothesis that we are pursuing in the center is that men
are at greater risk of developing diseases of motor control of
muscle because that is their fuel depot. Women will utilize
lipids as a fuel, and men can utilize muscle as a fuel to
generate glucose and ketone bodies from protein, the muscle
protein.
Our hypothesis is that across these age-associated
neurodegenerative diseases, there is a bioenergetic crisis in
the brain that then sends out this alert signal, ``I am
starving,'' and now it sends out that signal to female, to the
lipids, to men, to muscle, and it begins in the male, not
exclusively, but in the male to start basically reducing the
real estate that it has to maintain. The brain innervates every
muscle with thousands of fibers, axons that regulate muscle
control, so imagine now you are withdrawing that real eState
that you have to maintain.
These are hypotheses that the American relationship is
supporting, but more importantly, it actually gives us tow
things. It gives us a time window. We know that each of these
diseases has a prodromal or preclinical phase, so that is part
one, and part two, we can jump in and intervene. If we have the
right mechanism for these diseases, we can actually turn that
ship around early on.
Senator McSally. Great. What is the barrier, though, with
getting access to information?
Dr. Brinton. The barrier really is--so I will give you a
story, so, as scientists, we are pretty good at the science. We
are not so good at the business, but what happens now is that
in order for our discovery to actually reach the patient, we
have to now develop business skills and turn our attention away
from this scientific endeavor to now a commercialization
endeavor. Some of us are good at that, and most of us are not,
right?
Part of what I would really think--I think would really
advance is we have now a program that you are funding,
Accelerated Medicines Partnership in Alzheimer's Disease. We
have other programs in the SBIR, STTR, and the CAP program, the
Commercialization Acceleration Program. Imagine we took this
kind of accelerated medicine partnership model where we have
experts that can come together and advance commercialization,
and their job is to make certain that we commercialize.
When you talk to corporate America, they look at this and
think, ``Neurodegenerative disease? That is a money loser, and
it is going to take forever.'' Whereas, part of what we can do
in this space is connect with people who see the opportunities
for intellectual property, protection, and development, and can
see that way to yes.
Too often we run into no because it does take a different
type of support, as you well know. It takes a different type of
expertise, and I know that the Federal Government already
supports universities through the Bayh-Dole Act. Part of what
we now need is a network. We have expanded beyond typically
what universities can provide. We need that national network
that is devoted to commercialization, and their metric of
success is not the no. It is the yes.
Senator McSally. I want to followup maybe--with Dr. Atri. I
visited the Critical Path Institute last week.
Dr. Brinton. Yes. Oh.
Senator McSally. They were talking about such a consortium
of trying to bring together, as a nonprofit, industry and
universities and other research entities, and they specifically
have an area of focus on Alzheimer's. Are you guys interacting?
Dr. Brinton. Yes.
Senator McSally. Are you participating in that, or no?
Dr. Atri. Yes. I gave the keynote yesterday to the AAC
public conference.
Senator McSally. Oh, perfect.
Dr. Atri. We were in contact there. I am going to go visit
them. I think it is very important what they are doing with
integrating big data, actually with clinical trials. This is
really, really important. Data sharing is really, really
important.
If I may say something about women and what is happening to
them?
Senator McSally. Yes.
Dr. Atri. There is bad news, and I think all of this about
sex differences, et cetera, it just really is very complex, and
it needs more research.
Some of the good news is that particularly in this era of
education, women are getting more education, and they are
having more cognitive reserve actually because of it. It turns
out that on average, women for different reasons, maybe
evolutionary-wise, do very well with their executive function,
which is their frontal systems. Multitasking. Those things go
along with activities in daily living.
On average, women have performed better than men on those
things. With education, et cetera, catching up and women out-
performing men, that is actually one good news.
The bad news, I think, is that, yes, they are not only
affected more, two-thirds, but also disproportionately both
them and minorities get the burden of caregiving a lot more. No
one wakes up one morning and says, ``Oh, today I have all the
knowledge that I need for caregiving. I have all the knowledge
of speaking this new language that I need to speak with my
family members of how do I change the environment, how do I
care about myself,'' and I think that is really, really
important to provide that support.
One of the reasons that actually primary care clinicians
and other people do not want to deal with this is that they are
overwhelmed. They do not have the resources.
If we could somehow change the codes in some ways for it to
be more possible to have social work support, care navigation
on that side--and as a clinician, if a mole is removed, what
you get paid for that and reimbursement is much more than the
hours and hours of time that you actually can spend in giving
counseling to people and putting them on a different
foundation. I think that is really a big opportunity for us to
do that.
Regarding the veterans, I spent 6 years as a social
director of the Geriatric Research Education and Clinical
Center at the Bedford VA when I was also at Mass General. We
had a 100-bed inpatient facility. We called it the Special
Dementia Unit. Much of the work actually that we know about end
of life was done there, about feeding tubes not working, why
people pass, et cetera, and the philosophy of actually hospice.
We had clinics all the way through.
What I could tell you is that I think veterans have other
risk factors that may mitigate and lessen some of their
cognitive reserve. There is a tremendous amount of--again,
whether this is traumatic experiences, et cetera, there is
alcohol, which is a toxin, supravascular, so they tend to have
much more high blood pressure and lipid problems, heart
problems. All these things are bad for the brain, and so that
puts them at risk much more.
What I can tell you is that it was difficult to get things
done, and there was a lot of no's or nonresponses. We had about
15 percent of people in the system doing 85 percent of the
work.
I could tell you at the time--I am involved in clinical
trials around the world. I advise companies how to interpret
data, how to design clinical trials by using math, and I was at
that point a leader in a global trial in 30-something
countries, 450 sites, 3,000 patients. It took me years, and I
could not get it into our own VA because of local issues with--
everything had to go up to a funnel to a certain point, and
that is difficulty and that is actually one of the reasons I
left.
Senator McSally. Wow.
Senator Collins?
That is awful.
Dr. Atri. Sorry to bring that up, but it is true.
The Chairman. No. I am very glad you shared that with us.
That is very disturbing, someone of your ability to find it so
frustrating, and plus, think of the advances that are being
blocked, if that is the case.
Dr. Atri. Very deserving folks. Yes.
The Chairman. Thank you for telling us that.
Let me followup with you on a study that you released this
past summer on the true economic cost of Alzheimer's, and it
created quite a big splash. It garnered a lot of attention
because you measured societal costs. You looked at the costs to
Federal programs, and you also look at the costs imposed on
individuals and families and how insidious they are and how
early they start.
I can see Ms. Capp has had this experience and is nodding.
Do you have some specific recommendations on how we can
reduce the financial burden on families?
Dr. Atri. I think part of it, again, comes back all the
way--the first recommendation is that early detection. You have
to be able to detect it early enough and not blow it off. Then
once you detect it, we need these care support systems to be
able to provide to folks.
Some of the other recommendations have to do again with
really being able to measure in real time these costs, so these
are opportunities.
As you were saying, that app is great. Imagine if we can,
in real time, be able to integrate the health care cost for the
caregivers beforehand. The health care costs for caregivers are
twice as much. Someone is paying for that. An employer is
paying for that. Medicare is paying for that, so there is an
ability in some ways. If we could break down some of those
barriers and emerge electronic medical records with insurance
data bases and, in real time, get the impact on burden on
folks--and it spills on to the children also.
For years--again, 1 day you do not exactly wake up and say,
``Today I become a caregiver.'' It is this partnership where
you assume more responsibilities, and family members take on
more responsibilities and they miss work. We have to be able to
capture those things, and part of that is having realistic
cohorts not just for clinical trials but observation in the
real world and knowing actually what--if we are doing
interventions, whether diagnosing people early and detecting
things, what is the value for that? Where initially you take
all the folks in a comprehensive manner and with the social
worker, neuropsychologist, and do wrap-around care to prevent
falls, how much does that percolate through the system to the
end?
I can honestly tell you it makes a difference, but we are
not measuring it because we have not had sort of the efforts
that are required and some of the collaboration between
industry and also the Government, I think. Funding does help.
Dr. Brinton. I would echo what Dr. Atri said about the VA.
The VA has wonderful intentions. There is no question,
wonderful intentions.
Too frequently, there are massive numbers of barriers, and
you wait years, where you are at this constantly nano-steps to
the goal and by the time you get to the goal, you have actually
completed the project elsewhere.
I think, in many respects, our veterans are a unique
population. We have more women veterans now, and yet most of
our care is based on what was developed for the male veteran.
Part of what I would just echo is how do we get to yes, yes
in a way that protects patient identity, protects their data,
protects their privacy, and at the same time does not lose
their opportunity for cures.
The Chairman. I just have a couple more questions. One is
for you, Ms. Capp, and that is you talked very poignantly about
the isolation a caregiver can feel and the neglect of the
caregiver's own mental and physical health.
I wondered, as you were caring for your mother for so many
years, whether there was respite care available to you, because
what I found when I was trying to help my mother is living in
rural Maine, it just was not available. This is obviously a
much more populated area but did you use respite care?
Ms. Capp. We lived in Vermont when we took care of my mom,
and we found the same problems. There was not the support. The
Alzheimer's Association was the most significant support we
had, so, yes, it is very difficult.
I would like to go back, though, to an earlier comment that
was made about the caregiver and getting the right support to
the caregiver. There is an explosion of technology and research
going on that caregivers, once they figure out they are in the
role of the caregiver, have no idea what is available to them.
In the roles that are needed, yes, we need education roles
to people who are supporting caregivers in the medical
community and other communities. The social work aspect is
critical, but another role that is critically important--and a
colleague of mine left her role as a physician after caring for
her dad to do this--is a navigator role, someone who
understands what is available and can bring it to the caregiver
so it can be used.
I find so many places I am at where I am hearing about
technology that caregivers have absolutely no clue about, so
the navigating role is critical.
The Chairman. Thank you for bringing that up as well.
I want to end my questions on a more positive note. It is
to you, Dr. Brinton. I am impressed by listening to all the
different avenues of research that you are pursuing, from
estrogen to the brain, to looking at regeneration, which if we
can repair or replace, turn back on the protein that can
regenerate the neurons that have been destroyed by Alzheimer's,
how exciting that is.
This really leaves me very hopeful. I have to travel to the
Mayo Clinic, to the University of Pennsylvania, NIH, Jackson
Labs in my own State, and many other research centers because I
am so interested in what is being done. What I see happening is
for a long while, researchers were focused just on amyloid
plaque and doing research in the latter stages of the disease
when the neurons are already killed, have died, and even if
they could clear the plaque, function was not being restored.
Now because we have so much more funding invested, we can
look at everything from what you have mentioned, which I think
is so exciting, to lifestyle factors and start really
broadening the projects.
Every year when Dr. Francis Collins, who regrettably is no
relation to me, the head of NIH, would come testify before the
Senate Health Committee, on which I serve, I would ask him,
``How many promising applications do you get that you cannot
fund?'' and he got to anticipate I was always going to ask him,
so he would bring a chart and the good news is that has really
changed because of the investment that we have worked so hard
to secure.
I mean, when I first started working on this issue more
than 20 years ago, it was literally $400 million for
Alzheimer's, and there was no focus at all. It was just not a
priority.
For us to now be at $2.3 billion in the Senate version of
the Labor-HHS bill, which includes NIH funding, it has $2.8
billion, which is another addition, which we fought hard for,
it is just so exciting, and it really does give me hope.
I just want to thank all of you for the extraordinary work
that you are doing. I think it is so important, and I want to
thank Senator McSally for convening such a terrific group of
witnesses. It leaves me hopeful--it really does--that as we
battle this devastating disease that has claimed the lives of
too many and that affects not just the victims but their
families almost as much as it affects the victims, that we can
make progress, so thank you for the great work that all three
of you are doing, and thank you, Senator.
Senator McSally. Absolutely. Thanks, Senator Collins.
I have two general kind of ending-the-hearing questions
that I want to hear from each of you on. The first is we have
talked about what we can do and what we have done. The first is
continuing the strong funding for that research, so we are with
you on that, and we are going to continue to advocate for the
strong funding.
We have talked about some other legislation related to,
again, having the early ability for those under age 60 to get
access to the Older Americans Act, so we fully support that,
also, the other legislation I mentioned, the CHANGE Act related
to allowing individuals in their first assessment with
Medicare, annual assessments to be assessed.
There is also the HOPE for Alzheimer's Act, which is
related to also caregiving planning and education and all that.
Is there anything else that we can be doing at the Federal
level to address these issues?
Dr. Atri. On the diagnosis and care side, I think years
ago, for example, end-stage renal failure because, for some
reason, a special sort of a thing of itself. I think when you
look at the numbers, what we see, we do not have the workforce
to deal with what is happening.
People are not going to want go to geriatric psychiatry or
a cognitive neurologist or a geriatrician. This is not sexy and
glamorous. It does not pay very well. Even having just the time
or in the reimbursement and getting the teams around folks, I
think that is really, really important, and to be able to get
people to come into our field--because I really do not know. I
do a lot of education. I educate something like 20-, 30,000
clinician hours a year, and I have done that for 15 years, and
there is just so much knowledge that needs to go there but then
the next generation, who is going to take care of them? So we
need to somehow be able to invest in that. I think that is
really, really important.
Senator McSally. Thanks.
Dr. Atri. The other part I would say is helping companies
with patent life in some ways. Companies want to rush through
things. Having been an advisor all the time, people want to
rush through because they are worried how much patent life they
have, somehow working with them in a partnership, to be able to
give them the opportunity for the patents, et cetera, to be
longer, so they do not have to rush, so we can actually do this
work.
When we think about the funding for Alzheimer's disease, et
cetera, we are still in the nascency, honestly. When we look at
the other conditions--cardiovascular disease--why are people
living longer and coming down with this? It is because we have
done better with cancer and cardiovascular disease. I remember
when I went to med school, all my patients died when they had
HIV but if you look at the funding for those, they have been at
levels of 10 times of what was in Alzheimer's disease space for
30 or 40 years.
Thank you so much for advocating for this.
Senator McSally. Absolutely.
Dr. Atri. I think that is going to help us, but to
understand that the brain is very, very complex, and it is
going to take a bit of time.
Senator McSally. Great.
Dr. Brinton, anything else we can do?
Dr. Brinton. Yes. Thank you again for your commitment.
I would say that this catapulting us over the valley of
death is part one, and that is--so, for example, there is a
translational drug development program at the NIA. They just
awarded two major grants, one of which is JAX Labs is
participating actually in both of them.
If we could have a center, an initiative like that for
commercialization, that would be fantastic, where we get the
best minds, and their job is to get to yes.
Thank you for bringing up the patent. The patent on our
regenerative therapeutic runs out in 8 years, and that is not
good for commercialization, so thank you for bringing that up.
The other aspect is essentially how can we maximize, again,
coming back to the education of the next generation. We have a
training grant from the National Institute on Aging to train
the next generation of translational Alzheimer's researchers,
and if we could expand that, that would, I think, be fantastic
and bring in the next generation.
We also have a training grant through the NIH with the
Navajo Nation to bring those into the neuroscience space.
Thank you.
Senator McSally. Ms. Capp?
Ms. Capp. I would again thank you for all you have been
doing. You are certainly well versed on all of the initiatives
the Alzheimer's is interested in having you focus on.
As we have been focusing on the disease, we need more focus
on the caregivers, and the one space I would say we have not
covered today that I think is critically important is to get
companies to recognize the responsibility they have in
supporting caregivers. It is a bottom-line equation. If we can
help support working caregivers to be healthier, the companies
that they work for will have lower cost of medical care, et
cetera. It is a business initiative we have to take on.
Senator McSally. Ms. Capp, I am going to give you one last
opportunity to kind of close this out, and we have the media
here tonight and we will have a platform to speak to Arizonans
through the reporting on this hearing today.
As someone who has been through this very personally--I
know you have as well--if there is somebody out there in
Arizona today that knows something is just not quite right in
themselves or in someone that they love, who they love, what is
your message to them as to what you would encourage them to do
and where they can go?
Ms. Capp. I would tell them they are not alone. There are
so many people going through exactly the same thing, and we
find support in recognizing we are not alone.
I would encourage them to reach out. The Alzheimer's
Association has a 24/7/365 call line. They can go there.
I have a website. I communicate regularly with caregivers,
so find the resource, but start at the Alzheimer's Association.
Senator McSally. Wonderful. Thank you.
I am so grateful for your testimony today and everybody
participating in this hearing. This is such an important topic.
Senator Collins, thank you so much for coming here and
bringing the Aging Committee to Arizona, and I agree that
Arizona has a bold independent spirit and your testimonies
today show that we are really on the forefront to breaking
through here and addressing these issues, so thank you.
I think I have a few things to say that are official here.
The hearing record will be closed on November 8, 2019, so other
members of the Committee will have time to submit questions for
the record, and we will ask for responses in writing, so I
appreciate it.
This concludes this hearing. Thank you.
[Whereupon, at 11:45 a.m., the Committee was adjourned.]
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APPENDIX
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Prepared Witness Statements
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