[House Hearing, 115 Congress]
[From the U.S. Government Publishing Office]




                               BEFORE THE

                        GLOBAL HUMAN RIGHTS, AND

                                 OF THE

                      COMMITTEE ON FOREIGN AFFAIRS
                        HOUSE OF REPRESENTATIVES


                             FIRST SESSION


                           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/ 


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                      COMMITTEE ON FOREIGN AFFAIRS

                 EDWARD R. ROYCE, California, Chairman
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
    Wisconsin                        ADRIANO ESPAILLAT, New York
ANN WAGNER, Missouri                 TED LIEU, California
BRIAN J. MAST, Florida
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 
                      International Organizations

               CHRISTOPHER H. SMITH, New Jersey, Chairman
MARK MEADOWS, North Carolina         KAREN BASS, California
DANIEL M. DONOVAN, Jr., New York     AMI BERA, California
    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 
  University.....................................................    27
Richard Mohs, Ph.D., chief scientific officer, Global Alzheimer's 
  Platform Foundation............................................    35
Mr. Michael Splaine, principal, Splaine Consulting...............    41


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



                      WEDNESDAY, NOVEMBER 29, 2017

                       House of Representatives,

                 Subcommittee on Africa, Global Health,

         Global Human Rights, and International Organizations,

                     Committee on Foreign Affairs,

                            Washington, DC.

    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 
fee schedule.
    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 
the world.
    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 
of Health.
    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 
    Dr. Bernard?


    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 
global reach.
    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 
Alzheimer's symptoms.
    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 
your questions.
    Mr. Smith. Thank you so very much, Dr. Bernard, for your 
testimony and for your insights.
    Dr. Glass?


    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 
Alzheimer's disease.
    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 
absolutely essential.
    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 


    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 
setting currently.
    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 
earlier presentation.
    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 
sector money.
    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 
this heavily.
    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.
    Dr. Bera.
    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 
for patterns.
    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 
the progression.
    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 
this point.
    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 
genetic risk.
    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 
clinical study.
    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 
remember that.
    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 
be generalized.
    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 
enhance things.
    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 
be transformational?
    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 
us globally.
    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.


    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 
the illness.
    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 
at NYU.
    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 
formal support.
    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 
    Thank you.
    [The prepared statement of Ms. Mittelman follows:]

    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 
to you.
    Mr. Smith. Great. Thank you. We will look it up and 
download it and put it in. Thank you.
    Dr. Mohs.


    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 
secondary prevention.
    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:]

    Mr. Smith. Thank you so much for your testimony and, again, 
for your leadership as well. Thank you.
    Mr. Splaine.


    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 
Disease International.
    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 
early 1980s.
    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 
other witnesses.
    The facts are stark, and in the introduction to the 
hearing, Mr. Smith kindly cited the facts that I have on record 
as well.
    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 
aging plan.
    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:]

    Mr. Smith. Mr. Splaine, thank you very much. Thank you to 
your brother.
    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, 
France, Australia.
    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 
United States.
    So I think the task of the very small staff working on 
dementia at the World Health Organization--did I say that 
clearly enough?
    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 
tangible success.
    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 
little odd.
    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 
clinical trials.
    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 
are agreeing.
    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 
of view.
    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 
the box.
    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 
was actually----
    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 
leaning forward.
    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 
proverbial box.
    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.]


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