[Senate Hearing 110-722]
[From the U.S. Government Publishing Office]
S. Hrg. 110-722
FEDERAL RESPONSE TO THE
ALZHEIMER'S EPIDEMIC
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HEARING
BEFORE THE
SUBCOMMITTEE ON RETIREMENT AND AGING
OF THE
COMMITTEE ON HEALTH, EDUCATION,
LABOR, AND PENSIONS
UNITED STATES SENATE
ONE HUNDRED TENTH CONGRESS
FIRST SESSION
ON
EXAMINING THE FEDERAL RESPONSE AND ADVANCES BEING MADE TOWARD DEFEATING
THE EPIDEMIC OF ALZHEIMER'S DISEASE
__________
JULY 17, 2007
__________
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Pensions
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COMMITTEE ON HEALTH, EDUCATION, LABOR, AND PENSIONS
EDWARD M. KENNEDY, Massachusetts, Chairman
CHRISTOPHER J. DODD, Connecticut MICHAEL B. ENZI, Wyoming,
TOM HARKIN, Iowa JUDD GREGG, New Hampshire
BARBARA A. MIKULSKI, Maryland LAMAR ALEXANDER, Tennessee
JEFF BINGAMAN, New Mexico RICHARD BURR, North Carolina
PATTY MURRAY, Washington JOHNNY ISAKSON, Georgia
JACK REED, Rhode Island LISA MURKOWSKI, Alaska
HILLARY RODHAM CLINTON, New York ORRIN G. HATCH, Utah
BARACK OBAMA, Illinois PAT ROBERTS, Kansas
BERNARD SANDERS (I), Vermont WAYNE ALLARD, Colorado
SHERROD BROWN, Ohio TOM COBURN, M.D., Oklahoma
J. Michael Myers, Staff Director and Chief Counsel
Katherine Brunett McGuire, Minority Staff Director
______
Subcommittee on Retirement and Aging
BARBARA A. MIKULSKI, Maryland, Chairman
TOM HARKIN, Iowa RICHARD BURR, North Carolina
JEFF BINGAMAN, New Mexico JUDD GREGG, New Hampshire
JACK REED, Rhode Island LAMAR ALEXANDER, Tennessee
BERNARD SANDERS (I), Vermont JOHNNY ISAKSON, Georgia
SHERROD BROWN, Ohio ORRIN G. HATCH, Utah
EDWARD M. KENNEDY, Massachusetts MICHAEL B. ENZI, Wyoming
Ellen-Marie Whelan, Staff Director
(ii)
C O N T E N T S
__________
STATEMENTS
TUESDAY, JULY 17, 2007
Page
Mikulski, Hon. Barbara A., Chairman, Subcommittee on Retirement
and Aging, opening statement................................... 1
Burr, Hon. Richard, a U.S. Senator from the State of North
Carolina, opening statement.................................... 2
Zerhouni, Elias, M.D., Director, National Institutes of Health,
U.S. Department of Health and Human Services, Bethesda, MD..... 4
Prepared statement........................................... 5
Hodes, Richard, M.D., Director, National Institute of Aging,
National Institute of Health, U.S. Department of Health and
Human Services, Bethesda, MD................................... 8
Prepared statement........................................... 10
Gerberding, Julie, M.D., Director, Centers for Disease Control
and Prevention, U.S. Department of Health and Human Services,
Atlanta, GA.................................................... 14
Prepared statement........................................... 15
Eschenbach, Andrew von, M.D., Commissioner of Food and Drugs,
Food and Drug Administration, U.S. Department of Health and
Human Services, Rockville, MD.................................. 19
Prepared statement........................................... 21
Isakson, Hon. Johnny, a U. S. Senator from the State of Georgia,
statement...................................................... 26
ADDITIONAL MATERIAL
Statements, articles, publications, letters, etc.:
Clinton, Hon. Hillary Rodham, a U.S. Senator from the State
of New York, prepared statement............................ 40
(iii)
FEDERAL RESPONSE TO THE
ALZHEIMER'S EPIDEMIC
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TUESDAY, JULY 17, 2007
U.S. Senate,
Subcommittee on Retirement and Aging,
Committee on Health, Education, Labor, and Pensions,
Washington, DC.
The subcommittee met, pursuant to notice, at 3:17 p.m., in
Room 628, Dirksen Senate Office Building, Hon. Barbara
Mikulski, chairman of the subcommittee, presiding.
Present: Senators Mikulski, Burr, and Isakson.
Opening Statement of Senator Mikulski
Senator Mikulski. Good afternoon, everyone. This afternoon,
the Subcommittee on Retirement and Aging is hosting a
roundtable on the subject of the Federal agency response to the
epidemic of Alzheimer's. This is set up a lot more starchy than
what I had originally intended it to be because to me, it looks
like a hearing. If it looks like a hearing, it is a hearing but
we're not going to act like it's a hearing. We wanted a far
more casual, more interactive approach and I hope that we can
do this.
Today, the reason we're here and I really want to welcome
four very distinguished Americans who have devoted their life
to public health, to saving lives and to caring about the
people in the United States of America. Dr. Zerhouni, the Head
of the National Institutes of Health, Dr. Gerberding, our
Director for the Center for Disease Control and Prevention, Dr.
von Eschenbach, our Commissioner for Food and Drug
Administration and Dr. Hodes, who is the Director of the
National Institute of Aging and Dr. Hodes, we had a very robust
hearing on research a couple of weeks ago.
But today, where are we heading? Well, everyone knows the
data about Alzheimer's. Five million Americans are currently
living with it. As the baby boomers age, we expect to have more
of Alzheimer's in our community, a disease right now for which
there is no cure, yet the possibility of very realistic
cognitive stretch-out. One hundred years ago, it was the first
year that Alzheimer's was diagnosed but we don't want to wait
another 100 years to see what we can do.
In talking about this, what we realized is that was 10
years after the first diagnosis of HIV/AIDS that a cocktail was
produced that enabled people to live longer and to live better.
It was a stunning time of cooperation. The wonderful work at
NIH. Certainly our good friend, Dr. Fouche played a lead role
working with obscure viruses that led the way and paved the
way. It was the best of research. The Center for Disease
Control mounted this incredible medical detective work when
young men in San Francisco and throughout the country were
developing the disease that we began to recognize--and FDA
worked in this intense and concentrated way to see how we could
take the best of what we knew in research, what we were noting
in epidemiology to come with up where we were.
Well, we wonder if we're not at this point now, where we
need to think along the lines of where are we going with the
issue of Alzheimer's. What we wanted to discuss with you today
is the Federal response. To talk about what is happening in the
area of research but knowing where we are with research, how
this is being transmitted into essentially work that the CDC
can troubadour out for either prevention or what clinicians can
use. We've heard stories of one, misunderstanding and
misdiagnosis by well-meaning, primary care doctors. Patients
worry about what's happening to them and their family wonders,
what should they do and where could they turn?
At the same time, we know that there are drugs that are
being developed, drugs that are being explored but we wonder,
is there a kind of a focal point where, in the issue of speed,
we still maintain the very rigorous standards of safety and
efficacy and don't let our fear and our hope move things too
quickly but then, a sense of urgency.
So what we're looking for today is to hear where we are in
kind of much-needed research but at the same time, what we're
looking at as we mark up the Alzheimer's Breakthrough Research
Program, what we could be doing to help you be you? We need
you. We already count on you but what can we do to help you
deal with the fact that this is an epidemic and we look forward
to your thoughts and then we hope that we can progress in a
conversational way.
We expect to be able to really have a conversation. We
expect more of our people to come but we scheduled this meeting
in coordination with your very complicated schedules as well
and we appreciate your cooperation but there is an intense
debate going on, on the Iraq War and about the deployment of
our troops.
But we have here Senator Burr, our very wonderful colleague
from North Carolina whose passion for public health is well
known and his dedication to research and advancing medical
science is well known. So why don't you--and I see you're
wearing the purple colors of the Alzheimer's Association.
Opening Statement of Senator Burr
Senator Burr. Well, Madam Chairman, thank you. More
importantly, I'd like to also welcome this prestigious group of
panelists today. As I look down, doctor, doctor, doctor,
doctor, I'm not sure whether Dr. Gerberding's sign is
indicative of anything other than the fact that she brought her
own. But it is larger.
[Laughter.]
Senator Mikulski. It's kind of the new world order, isn't
it?
[Laughter.]
Maybe I ought to get a bigger one.
Senator Burr. A rose among thorns--Madam Chairman, I
commend you for your leadership and your support for
Alzheimer's patients, your passion on the issue and more
importantly, what I've had the opportunity to learn from you in
a short period of time. Again, I want to thank each of you for
taking time out from what I know is an incredibly busy schedule
and I've had the opportunity already once today to meet with
Dr. Zerhouni on some other issues.
I believe promising research exists for Alzheimer's. Each
of your agencies play an important part of how we treat, how we
educate, how we care for the 5 million individuals in the
United States living with Alzheimer's disease and the many more
who will be added as they age or become diagnosed.
As we know all too well, Alzheimer's is truly costly to
treat and quickly becoming a financial burden on the Nation's
health care system. Loved ones and family members are feeling
the financial and emotional burdens of Alzheimer's disease as
well. Ten million caregivers are providing 8.5 billion hours of
care each year, valued at $83 billion.
Simply put, we must find a disease modifying treatment.
There are many reasons for optimism. Both the public and the
private sectors have identified Alzheimer's as a priority for
research and development dollars and we've learned during our
last couple hearings that we're on the cusp of a number of
potential scientific breakthroughs, which is exciting. It's
critical that we translate the information learned through
research and through clinical practice and personal experiences
into effective public health practices and more importantly,
medical treatment.
I look forward to hearing how each of your agencies are
advancing in this very, very important research and stand with
the Chairman to say we are committed to try to explore any and
all avenues that provide a better level and quality of care for
patients and also provide us a way to fill that gap of a
disease that is extremely costly, not just to us but to
individuals and to their families and I thank the Chair.
Senator Mikulski. Thank you. Dr. Zerhouni, we're going to
ask you to kick it off. Dr. Zerhouni is the Director of NIH.
He's a respected leader in the field of radiology medicine. He
is a well known scholar, worked at Johns Hopkins as the Vice
Dean in the School of Medicine and has a distinguished history.
Then we'll go right down the line.
Dr. Zerhouni, we look forward to what you have to say but
it's not only where we are in research but one of our questions
is, can the Congress either through authorizing more
appropriations, do something that would really accelerate where
we are on breakthroughs, never underestimating the solid, basic
research that needs to go on. But how do you see this? What are
we doing and could we do more and what would be the best way to
do it? And of course, we want to hear from our very wonderful
head of the National Institute of Aging.
STATEMENT OF ELIAS ZERHOUNI, M.D., DIRECTOR, NATIONAL
INSTITUTES OF HEALTH, U.S. DEPARTMENT OF HEALTH AND HUMAN
SERVICES, BETHESDA, MD
Dr. Zerhouni. Well, Senator Mikulski and Senator Burr, it's
a pleasure to be here and to address your question, I think it
would be important for us to A, review a little bit of the
recent past and then tell you where we are and where we intend
to be, if we have the ability to follow the pathways that I
think are becoming very clear today.
Over the past 30 years, Americans have--the average life
expectancy of Americans has gone up by 6 years or about 1 year
every 5 years. What that means is that you have a 65-year-old
American today, their average survival beyond 65 is 18 years.
If you're 85, your average length of life is going to be 6
years longer or more.
And that has changed the demographics of our country, as
you well know and this is what makes Alzheimer's a disease that
has been with us a long time, a current priority and a future
urgency, if you will, that we need to address. We need to
address forthrightly with programs that I think will, at the
end, change the paradigm with which we treat chronic diseases
and the thing that is very obvious to us is that the landscape
of disease has changed and is continuously changing in the
country. As you mentioned, there is no doubt that our
population continues to age but a striking change is the fact
that chronic diseases now make up 75 percent of health care
expenditures and are continuing to grow at a rapid pace.
Alzheimer's disease is a major component of that, as you
said, where up to 4.5, 5 million individuals affected with this
disease but if you really think forward, you're going to have
up to 16 million Americans affected by this disease and as
Senator Burr mentioned, it is a costly disease.
So how do you change the paradigm? How do you really affect
the outcome of this disease? What does NIH need to do? What I
think is obvious is that with the completion of the human
genome and the discovery of fundamental causes of diseases,
especially diseases like Alzheimer's disease that are long-term
diseases where it's obvious that the disease started many, many
years before it struck the patient. What we need to do is
strike the disease before it strikes the patient.
This is what we call the ERO, the Four P's of the future of
medicine. Where we have to go from a paradigm where we wait for
the patient to get very sick, to intervene to an era where we
are much more predictive about who, how, when is a patient
going to suffer from Alzheimer's disease and that implies,
Senator, a different kind of research. We need to do research
not just on the late effects of a disease but on the early
effects and the early signs of the disease by developing
biomarkers.
The second is that these conditions require us to
understand not only the fundamental causes of the disease but
also to manage the symptoms of the disease and lessen the
burden of the disease on our patients. For example, we know
that patients with Alzheimer's disease suffer from depression.
They suffer from cognitive deficits and we need to intervene at
that level.
At the end of the process, what will be the ultimate
solution for us to usher in an era where we will be much more
predictive of the disease process being there 20 years before
it strikes; B, very targeted approaches to treating the disease
at the stage we find it, and; C, if we can pre-empt the disease
all together, that would be the ideal and we've shown that in
certain cases, we can. For example, last year we introduced the
vaccine to prevent cervical cancer and there are areas of
research that the National Institute of Aging is funding where
a vaccine is being entertained for Alzheimer's disease as well.
So we have to really cover the entire spectrum of the
disease and this is what I think needs to be understood. We
will not make progress unless there is total coordination
between all aspects of the disease process, remembering that we
are seeing correlation and associations between--in these
patients--between the presence of diabetes and the likelihood
of developing Alzheimer's disease, heart disease and
Alzheimer's disease.
We also know that the disease has great impacts on
caregivers and therefore the delivery of the care has to be
thought through and it has to be improved. So for researchers
today, earlier and more accurate diagnosis is going to be
critical. That will require a better molecular understanding of
the disease process in its earliest stages.
It will require us to develop biomarkers, the ability to
either through imaging or blood tests, to detect who is at risk
for Alzheimer's disease. The completion of the human genome has
given us hope that we will be able to find genetic signatures
of susceptibility for the disease. We are launching a genome
environment initiative that will allow us to find out if there
are environmental factors that accelerate or provoke the
development of Alzheimer's disease.
All in all, I think that the key here is the transformation
of our research from a curative paradigm of the past to the
pre-emptive paradigm of the future is truly within our grasp
and it is the priority that we should sustain and support
aggressively.
I think 10, 15 years ago, we didn't know what the causes of
Alzheimer's disease at the fundamental level were, we have
multiple theories of the disease. You will hear from my
colleague, Dr. Hodes, about the progress we're making but there
are still remaining challenges and the challenges, I think, in
this case, are that the opportunities for science to make a
difference are many but we will not succeed unless we have an
all-front attack on Alzheimer's disease, from the very moment
it starts, before anybody knows that the disease is there and
the patient feels no symptoms, to the moment it strikes. We
have to be able to do research across that entire spectrum.
Thank you very much.
[The prepared statement of Dr. Zerhouni follows:]
Prepared Statement of Elias A. Zerhouni, M.D.
Senator Mikulski and members of the committee, good afternoon. I am
Dr. Elias Zerhouni, Director of the National Institutes of Health
(NIH), an agency of the Department of Health and Human Services, and I
am pleased to be here today to talk about the advances we are making
toward defeating Alzheimer's disease (AD), a devastating condition with
a profound impact on individuals, families, the health care system, and
society as a whole.
Peer-reviewed reports estimate that up to 4.5 million Americans
ages 65 and older are currently battling AD. Moreover, the rapid aging
of the American population threatens to increase this burden
significantly in the coming decades: Demographic studies suggest that
if current trends hold, the incidence of AD will begin to sharply
increase around the year 2030, when all the baby boomers (born between
1946 and 1964) will be over age 65. By the year 2050, the number of
Americans with AD could rise to as many as 16 million.\1\ In addition
to the tremendous emotional and physical toll AD exacts upon patients
and their caregivers, financial costs of AD are high: Some experts
estimate direct and indirect costs of Alzheimer's and other dementias
to be more than $148 billion annually.\2\
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\1\ Hebert, L.E., et al. Alzheimer Disease in the US Population:
Prevalence Estimates Using the 2000 Census. Archives of Neurology 60:
1119-1122, 2003.
\2\ Alzheimer's Association, Alzheimer's Disease Facts and Figures:
2007. http://alz.org/national/documents/Report 2007_FactAndFigures.pdf.
Figure includes Medicare and Medicaid costs and the indirect cost to
businesses when employees are burdened with the care of persons with
Alzheimer's.
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AD's complex pathology and relentless clinical course have
presented daunting challenges for the medical and research communities.
However, the National Institutes of Health is poised to meet these
challenges through a comprehensive program of research into the
underlying causes, diagnosis, prevention, and treatment of AD.
At the most basic level, our understanding of the brain and
cognition in both normal aging and disease states is increasing rapidly
and exponentially. Advanced imaging technologies have opened a window
into the inner workings of the brain and made it possible to visualize
the brain's activity, including changes in the brain that could herald
the onset of disease, with a specificity that was impossible even a few
years ago. For example, the development of new tracer compounds such as
Pittsburgh Compound B, the first molecule that can be used to map
amyloid plaques (one of the pathological hallmarks of AD) in the brains
of Alzheimer's patients, could allow earlier diagnosis of AD and
facilitate the evaluation of new treatments.
Because research suggests that the earliest AD pathology begins to
develop in the brain long before clinical symptoms are apparent,
scientists are now searching for reliable, valid, and easily attainable
biological markers that can identify cases very early in the course of
disease. Early diagnosis of AD benefits affected individuals and their
families, clinicians, and researchers. For patients and their families,
a definitive early diagnosis provides the opportunity to plan for the
future while the patient can still take an active role in
decisionmaking. For clinicians, accurate early diagnosis facilitates
the selection of appropriate treatments, particularly as new
interventions are developed to stop or slow progression of symptoms.
And for researchers, earlier and more accurate diagnosis will
facilitate clinical studies of new therapies and preventive measures by
allowing clinical trials on early intervention, before cognitive loss
becomes significant. We expect programs such as the ongoing Alzheimer's
Disease Neuroimaging Initiative (ADNI), a public-private partnership
which Dr. Hodes discusses in his statement, to provide a wealth of
information about both brain pathology and biomarkers that can aid us
in early diagnosis.
Successful early diagnosis also depends upon the identification of
people who are at particular risk for developing the disease. Although
we do not yet fully understand what causes AD, it is apparent that
genes play an important role, and NIH is supporting the development of
new techniques to speed the identification of genes that are associated
with AD. For example, genome-wide association studies (GWAS) rely on
newly available research tools and technologies to rapidly and cost-
effectively analyze genetic differences between people with specific
illnesses such as Alzheimer's disease or diabetes and to healthy
individuals. Identifying the differences may facilitate our
understanding of genetic risk factors that influence the development or
progression of disease.
Several NIH Institutes recently launched, or are planning, GWAS
initiatives with the expectation that the results will eventually
accelerate the development of better diagnostic tools and the design of
new, safe, and highly effective treatments. NIH is also developing a
data-sharing policy for GWAS to harmonize the practices NIH-wide
through which data will be made available for research use.
As with other chronic diseases and conditions, however, genes are
only part of the story. In addition to the genetic component, cognitive
health can be influenced by concurrent medical conditions,
environmental factors, and even an individual's social environment. An
ongoing NIH initiative aimed at elucidating the underpinnings of
cognitive health and preventing disease is the Cognitive and Emotional
Health Project. The goal of this trans-NIH initiative is to assess the
state of epidemiologic research on demographic, social, and biologic
determinants of cognitive and emotional health in aging populations and
the pathways by which cognitive and emotional health may reciprocally
influence each other so that the most likely interventions for
maintenance of cognitive and emotional health may be targeted. As a
first step, a comprehensive review of measures that are associated with
maintenance of cognitive health has been published and was a starting
point for the development of the recently published Centers for Disease
Control and Prevention/Alzheimer's Association's Healthy Brain
Initiative: A National Public Health Roadmap to Maintaining Cognitive
Health.
By learning more about the diverse factors that may increase risk
of cognitive decline or AD, we hope to identify interventions that
could delay or prevent its onset. For example, we have learned from
epidemiologic studies that diabetes, a condition affecting nearly 21
million Americans,\3\ is associated with cognitive decline in older
people. ACCORD-MIND, an ongoing substudy of the NIH-supported Action to
Control Cardiovascular Risk in Diabetes (ACCORD) study, is currently
testing whether the rate of cognitive decline and structural brain
change in people with diabetes treated with standard care guidelines is
different than in people with diabetes who adhere to more rigorous
treatment.
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\3\ National Diabetes Statistics.'' National Institute of Diabetes
and Digestive and Kidney Diseases, 2005. http://diabetes.niddk.nih.gov/
dm/pubs/statistics/index.htm.
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The translation of findings from basic research into new
interventions to prevent or treat disease is another major focus of the
NIH. In recent years, new insights into amyloid, tau, and inflammatory
and oxidative stressors have enabled us, for the first time, to create
highly specific treatments for AD that are targeted at particular
molecules and processes in the brain; Dr. Hodes describes in his
statement some of the newer targets that have been identified through
this research. Some of those compounds have significant proprietary
potential and are currently undergoing preclinical and clinical study
by pharmaceutical and biotech companies. Others are being tested in
NIH-supported clinical trials.
Finally, NIH supports the national infrastructure that makes basic
and clinical research possible. For example, researchers at NIH-funded
Alzheimer's Disease Centers (ADCs) are working to translate research
advances into improved diagnosis and care for Alzheimer's disease
patients while at the same time focusing on the program's long-term
goal--finding a way to cure and possibly prevent AD. Areas of
investigation range from the basic mechanisms of AD to managing the
symptoms and helping families cope with the effects of the disease. ADC
staff conduct basic, clinical, and behavioral research and train
scientists and health care providers who are new to AD research.
The Alzheimer's Disease Cooperative Study (ADCS) is a major
Alzheimer's disease clinical trials effort. Now in its 16th year, the
goal of the ADCS is to plan and conduct clinical trials on promising
compounds designed to improve cognitive functioning, ameliorate
behavioral disturbances, slow the rate of decline, or delay the onset
of Alzheimer's disease. In general, the ADCS tests drugs that are not
typically studied by large pharmaceutical companies, such as drugs that
are off patent or were patented and marketed for another use but might
be useful for treatment of AD, or novel compounds from individual
investigators or from small companies without adequate resources for
clinical trials. ADCS studies thus fill an important resource gap
between the identification of a potentially useful compound and its
eventual adoption in clinical practice. October 2006, NIH announced a
$52 million award to the ADCS over the next 6 years to conduct several
new clinical trials. Dr. Hodes describes some of these upcoming
clinical trials in his statement.
An exciting trans-NIH initiative that will facilitate research into
AD and other neurological disorders is the NIH Blueprint for
Neuroscience Research. The Neuroscience Blueprint brings the 16 NIH
Institutes, Centers, and Offices that support neuroscience research
into a collaborative framework to coordinate their ongoing efforts and
to plan new cross-cutting initiatives. By pooling resources and
expertise, the Blueprint aims to accelerate neuroscience research and
to reduce the burden of nervous system disorders. Working together,
representatives from the partner Institutes, Centers, and Offices
identify pervasive challenges in neuroscience and any technological
barriers to solving them. This enables the Blueprint to support the
development of new tools, training opportunities, and other resources
to assist neuroscientists in both basic and clinical research. Each
year from fiscal year 2007 to fiscal year 2009, the Blueprint will
focus on one of three themes: Neurodegeneration, neurodevelopment, and
neuroplasticity. Four funding announcements related to the
neurodegeneration theme were released in fiscal year 2007. These
initiatives support the identification of biomarkers for
neurodegeneration, the development of new ways to deliver therapeutics
to the nervous system, and two interdisciplinary training programs in
neurodegeneration research.
Finally, NIH conducts a number of research studies that support
caregivers of AD patients. AD caregiving is highly stressful,
emotionally and physically, and Dr. Hodes will tell you about some of
the ways NIH works to develop and disseminate interventions to help the
millions of Americans who care for a loved one with AD. To further
explore the economic, social, and psychological costs of AD, the NIH
supports studies such as the Health and Retirement Survey, the leading
source of combined data on health and financial circumstances of
Americans over age 50. Now in its 14th year, the HRS follows more than
20,000 people at 2-year intervals, and gathers important data that
informs health care policy regarding AD and a number of other health
conditions.
It is important to note that the NIH cannot and does not conduct
its important work in a vacuum. We work closely with partners in
academia, in the private sector, and elsewhere in the government to
develop new diagnostic tools and methodologies, to conduct clinical
trials, to disseminate the results of our research, and to implement
new interventions and policies resulting from our research at the
community level. For example, the AD Neuroimaging Initiative is a joint
venture between NIH and a number of academic and industry partners.
Another is the AD Cooperative Study, which I described earlier, is
conducted in close collaboration with our partners at the University of
California-San Diego and scores of clinical sites across the Nation.
Compared to even a decade ago, the field of neuroscience is moving at
an extraordinary pace. We know, however, breakthroughs cannot come
quickly enough for the millions of Americans touched by Alzheimer's
disease. I can report to you today that real progress is being made,
and that we at NIH are committed to seeing that progress continues
toward treatment, and ultimately prevention, of Alzheimer's disease.
This concludes my statement, and I will be happy to discuss these
matters further with the subcommittee.
Senator Mikulski. Thank you, Dr. Zerhouni. We would now
like to hear from Dr. Hodes, who heads up the National
Institute of Aging and has been a long time advocate of what we
need to do on the concept of both basic research and
breakthrough and I think what we're looking for is, of course,
stay the course but what are your ideas and recommendations
here?
STATEMENT OF RICHARD HODES, M.D., DIRECTOR, NATIONAL INSTITUTE
OF AGING, NATIONAL INSTITUTES OF HEALTH, U.S. DEPARTMENT OF
HEALTH AND HUMAN SERVICES,
BETHESDA, MD
Dr. Hodes. Well, thank you, Senator Mikulski.
Senator Mikulski. We kind of have this sense of urgency and
to move the kind of breakthrough thinking along.
Dr. Hodes. Yes, you in your opening comments and Dr.
Zerhouni as well, have stressed the burden at present of
Alzheimer's disease--emotional, and financial to the public
health system as well as the urgency imposed by the demography
and the increased number of individuals who will age, hopefully
successfully, and be at risk.
As Dr. Zerhouni has stressed, the new paradigm of trying to
understand diseases from their earliest beginnings so one can
intervene at an early stage rather than treat at a later stage,
perhaps have their most impressive prototype where it's been
showed that years and indeed, decades before the disease can be
identified clinically, there are changes in the brain that can
be detected.
For this reason, the research supported by NIH and I should
in collaboration with the other agencies here, have focused
broadly to find risk factors for disease, which can be
translated into opportunities for intervention. These clues
have come from a number of directions. They come from basic
science, where genetics has been most informative, identifying
the genes which can pre-dispose or cause Alzheimer's and
providing, therefore, targets that have been translated, in
fact, in clinical trials, to a point to which we could
intervene in that process.
As recently as a few months ago, yet a new Alzheimer's risk
factor gene, SORL1, was described and this impetus has
continued in now a formalized genetics initiative, which is
typical of the directions researchers are taking now in that.
This initiative, for example, is collecting 1,000 families with
multiple members with Alzheimer's disease.
This goes far beyond the work that any single investigator
or academic institution can do. It's a coalition of
investigators that are generating these data, who can be made
available to the whole international and national community of
investigators and this, I think, in terms of breakthroughs and
trends, is one of the advances we're making to move from
privatized research to research that becomes maximally
leveraged in populations of scientists. In addition, we're
learning about risk factors that accompany epidemiologic
studies. As Dr. Zerhouni alluded to, the risk factors for
cardiovascular disease such as hypertension earlier in life,
diabetes, increased homocysteine levels are all associated as
risk factors and these, too have led to translation to clinical
trials, intervening in each of these variables in an attempt to
determine whether the causal link can be made and indeed,
intervention to these variables will have an impact on
preventing or slowing progression of Alzheimer's disease.
It's stressed, appropriately, the importance in all of
these studies for identifying the disease early so that one can
make early diagnosis and can track progression. Most
importantly perhaps, is that one can identify more accurately
and more rapidly the effect, positive or negative of any of the
interventions and trial and among the markers being used to do
this, as Dr. Zerhouni alluded to, are markers that come from
nerve imaging techniques. Quite striking in the last years,
we've seen the development, previously unimaginable, of dyes
that can actually identify both plaques and tangles, the
lesions in the brain of Alzheimer's patients in the living
patient and the hope is that by tracking the progress of this
and the ability of drugs, vaccines, other interventions to
arrest this progression, we can have far more cost efficient
and more rapid answers to clinical trials that are underway.
An initiative called the Alzheimer's Disease Neuro Imaging
Initiative is really a landmark of its kind. I think it
stresses the kind of innovation in terms of collaboration that
is required. This is an initiative that is looking at a number
of older American men and women who either have no disease,
have mild cognitive impairment or have Alzheimer's disease and
it's over time, following them for their clinical state, their
psychological testing results, their new imaging results as
well as the results of tests of cerebral spinal fluid and serum
and other evidence of biological markers, including genetics.
What's noteworthy about this initiative is that it will
create a panel of materials that will be used, once again, by
all qualified scientists and equally remarkable, is the nature
of the partnership involved. This initiative was carried out by
NIA in collaboration with other institutes at NIH with very
close association with the FDA, recognizing that the progress
in this initiative has to feed into the ability of the FDA to
access the efficacy of drugs. It involves as well, partnership
with more than 20 pharmaceutical companies and the bio-
technology companies who are contributing not only their
expertise but funding, recognizing that the outcomes of studies
such as this will serve all of the public and private sectors
with a common goal of identifying ways to intervene
successfully in Alzheimer's disease.
So long as we are progressing in this direction, so long as
we are faced with Alzheimer's disease to be cared for, we also
need to be cognizant of the burden on caregivers. As Dr.
Zerhouni noted and was noted in the introductory comments as
well, the burden on those taking care of loved ones, family
members, people with Alzheimer's disease is itself, huge. It
has an impact not only financially but on the health and mental
State of those taking care of individuals with Alzheimer's
disease. We're happy to identify the results of the clinical
trial, which was targeted, in this case, at Caregivers, an
intervention that can improve the State of caregivers. The
study was successful, in fact, identifying the kind of
intervention that can reduce stress and improve quality of
life, both for those afflicted with the disease and those who
care for them.
So long as we are progressing in the direction of
preventing disease and treating those already afflicted, as
well as easing the burden of those providing important care for
them. We will continue in our collaboration across agencies,
across sectors to this end.
Finally, in all of this, we maintain the sense of
responsibility that was enacted in the congressional
establishment of a facility through NIA in leadership to
provide information to the public, not only a clearing house
for publications but a multimedia effort to keep the public
informed of progress of the state of medical knowledge, of
needs to recruit people and their interests into clinical
studies in support of our overall enterprise.
I thank you again for this opportunity to speak with you
and to continue our long and I hope, soon to be, successful
partnership in attacking Alzheimer's disease.
[The prepared statement of Dr. Hodes follows:]
Prepared Statement of Richard J. Hodes, M.D.
Senator Mikulski and members of the committee, thank you for
inviting me to appear before you today to discuss Alzheimer's disease
(AD), an issue of interest and concern to us all. I am Dr. Richard
Hodes, Director of the National Institute on Aging (NIA), the lead
Federal agency for Alzheimer's disease research. NIA is one of the 27
Institutes and Centers that comprise the National Institutes of Health
(NIH), an agency of the U.S. Department of Health and Human Services
(HHS). I am delighted to be here today to tell you about the progress
we are making toward understanding, treating, and preventing AD.
Dr. Zerhouni's statement cites the number of Americans whose lives
are deeply affected by AD. The numbers are indeed stark and are growing
with the aging population. But there is another part of the Alzheimer's
story that we can tell; although AD remains a major public health issue
for the United States, we have made, and are continuing to make,
dramatic gains in our ability to understand, diagnose, and treat the
disease. This progress offers us hope of reversing the current trends
so that the risk of AD can be reduced for millions of older adults and
their families.
As the lead Federal agency supporting AD-related research, the
National Institute on Aging conducts and supports a portfolio of
research that encompasses topics across the spectrum of AD-related
inquiry. Active areas of research include basic brain biology, pre-
clinical and clinical research on potential interventions, and
population-based assessment of the epidemiology, economic, social and
psychological costs of dementia to the family and society. Our research
agenda is broad, and we pursue that agenda in partnership with
scientists across the Nation. In October 2006, NIA convened a major
scientific planning meeting to discuss future directions for
Alzheimer's disease research at NIH, with particular attention to
research issues that need to be addressed in order to improve diagnosis
and treatment of AD. This meeting brought together internationally-
recognized experts in the field, and the results will influence the
direction of the research we support over the next few years.
RISK FACTORS AND EARLY DIAGNOSIS
Identification of risk factors for AD may enable us to develop
interventions to delay or even prevent its onset, and NIA-supported
researchers are making important advances in several key areas.
Genetics. Discovery of risk factor genes will help illuminate the
underlying disease processes of AD, open up novel areas of research,
and identify new targets for drug therapy. Researchers recently
determined that variations in a gene known as SORL1 may be a risk
factor for the development of late-onset AD. While this discovery
provides a new genetic clue about the late-onset forms of AD, further
research is needed to determine the role of SORL1 in AD pathogenesis.
Research is continuing in this important area through the AD
Genetics Initiative, which to date has recruited nearly 1,000 families
to establish a resource for studies of the genetics of late-onset AD.
In addition, NIA has established a national genetics data repository to
facilitate access by qualified investigators to genotypic data for the
study of the genetics of late-onset AD. Investigators have already
begun submitting data to this repository and requesting additional data
for genetic studies. We also expect genome-wide association studies,
mentioned by Dr. Zerhouni, to provide important information about AD's
genetic underpinnings.
Health Conditions Affecting Risk. Population studies suggest that
conditions affecting cardiovascular and cerebrovascular systems may be
associated with higher risk for dementia or that the presence of
vascular disease may influence the progression of AD. One recent report
indicated that AD dementia may be exacerbated by other cerebrovascular
problems such as small strokes, while another linked untreated high
blood pressure in mid-life with increased risk of dementia in later
life. The possible association of diabetes, insulin resistance, and AD
is garnering increased attention as well. Recent findings from at least
four long-term studies link diabetes with decline in cognitive
function. The NIA is currently supporting three clinical trials to
examine directly whether diabetes-related interventions might be
effective in preventing or delaying cognitive decline or development of
AD or AD progression.
Early Diagnosis: Advances in Neuroimaging. Research suggests that
the earliest AD pathology begins to develop in the brain long before
clinical symptoms yield a diagnosis. Therefore, it is critical that we
find a way to detect signs of the disease at the earliest point
possible so that we can test interventions and, ultimately, treat the
disease as early as we can. Toward that end, the NIA has embarked on
ambitious efforts to find new ways to measure AD changes in the brain
or in other systems including blood and cerebrospinal fluid. These
programs are already yielding results. Improvements in brain imaging,
coupled with the development of more sensitive cognitive tests, are
enabling us to diagnose AD in the research setting with greater
precision than ever before. The discovery of compounds such as
Pittsburgh Compound B and, more recently, FDDNP that enable the
visualization of AD's characteristic amyloid plaques and
neurofibrillary tangles in the living brain--an impossibility only a
few years ago--will not only enable scientists to diagnose AD earlier,
but may also help researchers and clinicians develop new treatments and
monitor their effectiveness, as well as reduce the time and cost of
clinical trials.
Research in this area has been intense and productive. The
Alzheimer's Disease Neuroimaging Initiative (ADNI) is currently the
major venue for facilitating neuroimaging research relevant to AD.
Early results from ADNI show that, in addition to aiding early
diagnosis, researchers may be able to reduce the time and expense
associated with clinical trials by improving methods and developing
uniform standards for imaging and biomarker analysis. For example, one
ADNI study found that a standard physical model can be used
successfully to monitor performance of MRI scanners at many different
clinical sites; this will help ensure accuracy of the MRI images
produced from ADNI volunteers. Investigators on another ADNI study
compared changes over time in PET scans of brain glucose metabolism in
people with normal cognition, mild cognitive impairment, and AD, and
they found that scans correlated with symptoms of each condition and
that images from different clinical sites were consistent across sites,
suggesting the validity of PET scans for monitoring the effectiveness
of therapies in future clinical trials. This study will continue to
provide a foundation for future efforts to identify biomarkers.
An important achievement of ADNI is the creation of a publicly
accessible database available to qualified researchers worldwide. The
database contains thousands of MRI and PET scan brain images and
clinical data and will include biomarker data obtained through blood
and cerebrospinal fluid analyses. ADNI includes samples and brain scans
from 200 people with Alzheimer's, 400 people with mild cognitive
impairment and 200 cognitively healthy people. All volunteers are
between ages 55 and 90. Confidentiality of the participants is
rigorously protected. To date, over 200 researchers have signed up for
database access.
TRANSLATIONAL RESEARCH: MOVING BASIC FINDINGS INTO CLINICAL PRACTICE
New findings about AD's characteristic pathology are leading to
insights that may eventually inform treatment strategies. Amyloid and
amyloid-producing enzymes, tau, oxidative damage to the brain, and
mediators of inflammation are all under consideration as treatment
targets, and investigators are also looking at new ways to protect
brain cells as they age and to validate ways to enhance memory and
improve cognition with age. For example, recent discoveries have
provided support for the validity of beta-secretase (BACE1) as a
therapeutic target. BACE1 comes from a family of enzymes known as
secretases that cut, or cleave, the amyloid precursor protein (APP) in
the brain; working in concert with a partner enzyme, gamma secretase,
BACE1 is responsible for the formation of amyloid in AD. In a recent
study, NIA-supported investigators were able to silence the production
of BACE1 in mice that were genetically engineered to develop AD-like
pathology. They found that reducing BACE1 levels slowed the production
of amyloid plaques and diminished the damage to neurons and synapses in
the brains of the mice receiving the treatment. Notably, the mice in
which BACE1 production was halted had less difficulty learning a new
task than control mice. NIA's Translational Research Initiative aims to
speed research across the continuum of intervention development, from
drug discovery to full-scale clinical trials. Components of the effort
include grant solicitations to stimulate the discovery, development,
and preclinical testing in cellular, tissue, and animal models of novel
compounds for the prevention and treatment of the cognitive impairment
and behavioral symptoms associated with AD. The ultimate goal of this
initiative is to facilitate submission of investigational new drug
applications to the Food and Drug Administration so that more clinical
trials testing promising therapies can be started. NIA also supports
toxicology services for investigators or small companies that have a
potentially viable candidate drug for AD treatment but lack the
resources to begin the formal drug testing process.
In addition, NIA is currently supporting approximately 25 AD-
related clinical trials. These include studies of:
Physical exercise, which epidemiological studies suggest
may have a specific influence on aspects of cognitive decline. Small
clinical trials are currently testing the effects of exercise on
cognitive decline and brain function, both in older adults with normal
cognition and in persons with mild cognitive impairment with memory
decline.
Statins, which lower cholesterol levels, to determine
whether these drugs can modify disease progression in people with mild
AD.
Valproate, which is used to treat epilepsy and some
psychiatric disorders, to determine whether this drug can slow decline
or help delay the agitation and psychosis that often accompany AD.
Dr. Zerhouni mentioned in his statement that the Alzheimer's
Disease Cooperative Study will implement several new clinical trials
over the next 6 years. One, a study to determine whether
docosahexaenoic acid (DHA), an omega-3 fatty acid, will slow cognitive
decline in AD, has begun recruitment. Other trials planned by the ADCS
include:
Intravenous Immunoglobulin (IVIg). IVIg, a form of passive
immunization, contains naturally-occurring antibodies against beta-
amyloid, and preliminary studies have shown that IVIg promoted
clearance of beta-amyloid from cerebrospinal fluid, as well as improved
cognition in AD. The new ADCS trial will demonstrate whether IVIg is
useful clinically for treating AD.
Lithium. Lithium, commonly used to treat bipolar disorder,
has been shown in animal studies to block abnormal changes in tau and
to regulate beta-amyloid. ADCS investigators will undertake a pilot
biomarker study to see whether the drug can lower tau and beta-amyloid
levels in cerebrospinal fluid and be safely tolerated in older AD
patients.
We have also been encouraged by several recent studies related to
AD prevention and the maintenance of cognitive health in old age. In
2006, results from the Active Cognitive Training for Independent and
Vital Elderly (ACTIVE) study demonstrated for the first time in a
randomized, controlled trial that certain mental exercises can offset
some of the expected decline in older adults' thinking skills and show
promise for maintaining cognitive abilities needed to do everyday tasks
such as shopping, making meals, and handling finances. Some of the
benefits of the short-term training tested in this study lasted for as
long as 5 years. Investigators also recently announced the discovery of
the first agent shown to delay the clinical diagnosis of Alzheimer's in
people with amnestic mild cognitive impairment (MCI), an MCI subtype
strongly correlated with the later development of AD. The investigators
found that individuals who took the drug donepezil (Aricept) were at
reduced risk of progressing to a diagnosis of Alzheimer's disease
during the first year of the trial. In addition, there was benefit over
a longer 2-year period that was limited to those individuals positive
for the APOE-4 gene allele, which confers a strong predisposition to
the development of late-onset AD. Although donepezil's effects were
limited, the results are nonetheless encouraging. And although too
little is known about donepezil's long-term effects to support a
recommendation for its routine use to forestall the diagnosis of AD in
people with mild cognitive impairment, these findings do suggest that
chemoprevention of AD is possible and support our hope that future
clinical studies will lead to more significant progress.
CAREGIVER SUPPORT
Most Americans with AD today are cared for outside institutional
settings by an adult child or in-law, a spouse, another relative, or a
friend. Research has shown that the stress of caring for a loved one
with AD can have a profoundly negative impact on health and well-being.
NIA-supported investigators have found that a personalized intervention
consisting of home visits, structured telephone support sessions, and
telephone ``check-ins'' can significantly improve the quality of life
for AD caregivers. The study, Resources for Enhancing Alzheimer's
Caregiver Health II (REACH II), was funded by NIA and NIH's National
Institute of Nursing Research and is the first randomized, controlled
trial to look at the effectiveness of an AD caregiver support
intervention for ethnically diverse populations. Follow up studies are
needed to examine how the intervention might be used through existing
community networks of health and aging services.
OUTREACH TO THE PUBLIC
Since its inception, NIA has provided the public and health
professionals with information about Alzheimer's disease and age-
related cognitive change. Twenty-one years ago, Congress established
NIA's Alzheimer's Disease Education and Referral (ADEAR) Center to
``compile, archive, and disseminate information concerning research,
demonstration, evaluation, and training programs and projects
concerning AD and related dementias.'' Today, that mission is being
accomplished through a wide variety of materials, resources, and
activities for the general public, health professionals, and people
with Alzheimer's disease and their families.
ADEAR's programs are active and comprehensive. For example, the
number of print materials distributed went from about 377,000 in 2005
to more than 645,000 in 2006. As more and more Americans turn to the
Internet for health information, the Center has experienced a striking
increase in the number of web visits, up from 1.9 million in 2005 to
2.9 million in 2006. Further, the NIA and ADEAR Center staff, based in
Silver Spring, MD, proactively invite the public to use its resources.
In 2006, the ADEAR Center distributed 43 e-mail alerts to various
subscriber lists, letting subscribers know about research news, new
publications, and other updates.
The effectiveness in developing information products and strategies
is based in part on the NIA's collaborations with agencies, academic
institutions, and other organizations. The success of new easy-to-read
publications involved collaboration between the ADEAR Center and the
NIA's network of Alzheimer's Disease Centers. A new project aims to
respond to a lack of materials for the newly emerging audience of
people with early-stage AD and their families. In this effort, ADEAR is
working with the Northwestern University School of Medicine's
Alzheimer's Research Center to produce a publication What Happens Next:
A Booklet About Being Diagnosed with AD and Related Disorders. The
booklet is actually written by early-stage patients to provide those
newly diagnosed with resources and with comfort and support from others
who have walked the same path.
CONCLUSION
It is difficult to predict the pace of science or to know with
certainty what the future will bring. However, the progress we have
already made will help us speed the pace of discovery, unravel the
mysteries of AD's pathology, and develop safe, effective preventions
and treatments, to the benefit of older people and their families.
Thank you for giving me this opportunity to share with you our
progress on Alzheimer's disease. I would be happy to answer any
questions you may have.
Senator Mikulski. Well, we'll come back to you but now we
want to hear from Dr. Joy Gerberding, our Director of the
Centers for Disease Control and Prevention. I want to
acknowledge the fact that our colleague from Georgia, Senator
Isakson, has joined us. He has a long time, both personal and
professional interest in this issue and his advocacy is really
most welcome, his prudent advocacy on this committee.
Dr. Gerberding, we're anxious to hear from you. You've been
at CDC now for 10 years and you were there as the Deputy
Director for Infectious Disease, dealing with things like
Anthrax, but now tell us how you're going to deal with another
A word. But we really count on CDC for this kind of news that
you can use.
STATEMENT OF JULIE GERBERDING, M.D., DIRECTOR, CENTERS FOR
DISEASE CONTROL AND PREVENTION, U.S. DEPARTMENT OF HEALTH AND
HUMAN SERVICES, ATLANTA, GA
Dr. Gerberding. Thank you very much and CDC is very
privileged to be here and to have a chance to speak to our
Senators and we thank Senator Isakson for coming. We really
appreciate the support the Georgia delegation brings us as
well.
You know, when you think about Americans, all of us are
aging and when you think about what people really want when
they age, they want to be able to work productively and then
retire and enjoy some leisure time, do the things that they
missed doing when they were working. They want to enjoy their
loved ones and their friends. They want to be able to
contribute to their communities and I think most of all, they
want to be independent.
But what do Americans fear? Well, about 30 percent of them
fear loss of physical functioning but about two-thirds of them
are afraid that they are going to lose their mental capacity
and sadly, for about 4.5 million people today, the worst has
happened. They have developed Alzheimer's disease and they
really truly are suffering the most severe form of cognitive
impairment.
What we need to focus on is not just the 4.5 million people
who are robbed of their independence. I like to think of this
as the great brain robbery because it truly does take away
people's ability to do the things that they value most in life.
But we also need to think about their caregivers who are
profoundly impacted, about 7 out of every 10 people with
Alzheimer's disease live at home and we need to remember that
there are things that we can do today to help ameliorate this
burden on individuals, their caregivers and our society.
I want to thank Congress for supporting CDC to bring
together the collaboration that helped create this roadmap, the
Healthy Brain Initiative. This represents the input of many
people at this table but I would also like to acknowledge a
quartet of people who are not here today and that would be
Josefina Carbonell from the Aging Group at HHS, Betty Duke from
HRSA, Carolyn Clancy from AARC and Leslie Norwalk from CMS, in
four other agencies and those women would have big signs, too,
if they were here at the table because they've made some
tremendous contributions to this issue and I think across HHS,
we recognize that Federal leadership really is important but we
also need to work with the Alzheimer's Association and others
to create and enact this kind of roadmap.
There are two tragedies. One is the tragedy of not knowing
what to do and you've heard, I think, some of the exciting
research that our collaborators at NIH are working on. You'll
hear from Dr. von Eschenbach about what the FDA can do. So
there is the tragedy of not knowing and I think we are
investing in learning more and being able to do more.
But there is also the current and ongoing tragedy of not
doing what we know and I think that's what this roadmap is all
about, that there are things that we can and should be doing
now. We need to make a commitment. We need to inspire people to
share that commitment. We need to build the partnerships and I
think most importantly, we need to get the word out that
prevention is possible.
We already know that vascular disease is a major risk
factor for the development of cognitive dysfunction. There are
some hints that physical activity may be important, some early
hints that maybe diabetes, exposure to passive tobacco and in
fact, if you look at the health promotion agenda for health
aging, many of the things that we should already be
recommending to our seniors are the same constellation of
things that may end up having a very important role in
protecting cognitive health as well.
So we need to reach out and help seniors achieve the best
possible health span and I think importantly, that includes a
much greater emphasis on cognitive health.
I'd just like to end with one little vignette of hope.
There is a wonderful program that was supported in Seattle, in
part through one of CDC's Prevention Research Centers, whom
were using some volunteer physical trainers in the community
facility for seniors. They initiated an exercise program and
what they were able to show with a very small investment that
the participating seniors had better balance. They were overall
better fit. They were happier. They reported better mental
health and most importantly, their program was associated with
a 23 percent reduction in group health expenses. So a very
small investment, a very significant improvement in health,
even for some very senior people and I think it means that we
have to never give up. There is always room for health
promotion and always room for prevention at every age. Thank
you.
[The prepared statement of Dr. Gerberding follows:]
Prepare Statement of Julie L. Gerberding, M.D., M.P.H.
Good afternoon, Madam Chair, Senator Burr, and distinguished
members of the subcommittee. I am Dr. Julie Louise Gerberding, Director
of the Centers for Disease Control and Prevention (CDC) within the
Department of Health and Human Services (HHS). Thank you for the
opportunity to be here today to talk with you about the importance of
safeguarding the cognitive health of our Nation's aging population. We,
at CDC, share your commitment to doing all we can to address the impact
of cognitive impairment, which includes Alzheimer's disease and other
forms of dementia. We recognize the impact it has on individuals,
families and society. As you know, the numbers of people with
Alzheimer's disease and other dementias are expected to increase
substantially over the coming decades unless these conditions can be
prevented.
Thanks to funding provided by Congress, CDC has established an
Alzheimer's disease segment within the Healthy Aging Program, which we
refer to as the Healthy Brain Initiative. We have reached out to
collaborate with the National Institutes of Health and the
Administration on Aging, and we have formed a strong partnership with
the Alzheimer's Association. A critical outcome from this partnership
is the release last month of The Healthy Brain Initiative: A National
Public Health Road Map to Maintaining Cognitive Health. I will tell you
more about this Road Map shortly.
With the increase in life expectancy over the past century, most
older adults look forward to having a long life. However, one of the
greatest worries about living to age 75 and beyond revolves around
memory loss.\1\ The public's concerns about losing their mental
capacities as they age are also reflected in a recent national poll
conducted by Research!America.\2\ When asked to think about aging and
losing either physical or mental capacity, 62 percent of respondents
indicated they feared losing their mental capacity as compared to 29
percent who feared losing their physical ability. These fears of
declining mental capacity and Alzheimer's disease have led to increased
attention by the public, the media and public health professionals.
Despite all the attention, the public and even many health care
providers still know very little about the specific factors that
increase a person's risk of experiencing cognitive decline.
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\1\ American perceptions of aging in the 21st century. Washington,
DC.: The National Council on Aging, Inc., 2002.
\2\ Research!America. America speaks. Poll data summary, volume 7.
Alexandria, VA: Research!America; 2006. http://www.researchamerica.org/
polldata/2006/mentalhealth9-06.pdf (slide 6).
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CDC recognizes the importance of considering the entire person and
not focusing on physical health alone. One of our four key Health
Protection Goals is to ensure that all people, and especially those at
greater risk of health disparities, will achieve their optimal lifespan
with the best possible quality of health in every stage of life. This
holistic approach takes into account mental and cognitive health as
well as physical health.
I would like to briefly define cognitive decline and talk about how
the aging of our population is expected to affect the national burden
posed by cognitive impairment. I will then talk about the role of
public health, including a brief highlight of our achievements to date
and where we expect to take these activities in the future.
DEFINITION OF COGNITIVE DECLINE
Much like physical health, cognition can be viewed along a
continuum--from optimal functioning to mild cognitive impairment to
severe dementia. While there are certain cognitive changes that occur
with age--what we call normal age-related changes--such as a slower
pace of learning and the need for new information to be repeated,
cognitive decline is not a normal part of aging. It is more serious.
Cognitive decline can range from mild cognitive impairment to severe
dementia, but these two conditions are not necessarily manifestations
of the same condition. Many people never develop any serious decline in
their cognitive performance and those who develop mild cognitive
problems do not necessarily develop dementia or Alzheimer's disease.
IMPLICATIONS OF A RAPIDLY AGING POPULATION
The aging of the U.S. population is expected to place demands on
our public health system, medical services and social services. The
growth in the number and proportion of older adults is unprecedented in
the history of the United States. A hundred years ago, only 3 million
people in this country were aged 65 or older. Today, more than 36
million Americans are in this group, and that number is expected to
grow during the next 25 years to more than 70 million as the baby
boomers age. Public health's prevention efforts and improved medical
care have contributed to a significant increase in life expectancy in
the United States during the past century. However, this success has
been accompanied by a major shift in the leading causes of death for
all age groups, including older adults, from infectious diseases to
chronic and degenerative illnesses. Alzheimer's disease is one of the
top 10 leading causes of death. We know Alzheimer's disease and
cognitive impairment have economic costs and impacts on individuals and
their families. Recent scientific advances have highlighted potential
risks associated with cognitive decline and may ultimately pave the way
for preventing cognitive decline.
Alzheimer's disease and cognitive impairment can cause years of
disability, and loss of function and independence. We must focus on
preventing or delaying disability and the loss of function. Although
the risk for disease and disability clearly increases with advancing
age, poor health is not an inevitable consequence of aging. It is a
priority for all of us that we work to find ways to prevent or postpone
functional loss including losses to physical, mental and cognitive
health.
BURDEN OF COGNITIVE DECLINE
In the United States, the burden of cognitive impairment has been
expressed mainly in terms of prevalence, incidence, and mortality for
dementia generally or for Alzheimer's disease in particular. An
estimated 4.5 million people currently have Alzheimer's disease, and
census population projections indicate that by 2050, as many as 16
million individuals will have the disease. More recently, prevalence
statistics for mild cognitive impairment have become available. Mild
cognitive impairment refers to a level of impairment that is more
serious than normal age-related changes, but it is not as severe as
Alzheimer's disease or other forms of dementia. Studies from the United
States and Canada have suggested that mild cognitive impairment may be
a problem for 16-25 percent of older adults aged 65 years and older.
SOCIETAL AND ECONOMIC IMPACT
Alzheimer's disease and other dementias place a costly burden on
the Nation's health care system. Individuals with Alzheimer's disease
make up less than 13 percent of the Medicare population, yet they
account for 34 percent of Medicare spending (approximately $91 billion
in 2005). In 2000, Medicare spending for persons with Alzheimer's
disease and other dementias was nearly three times as much, on average,
as spending for individuals without these conditions (Urban Institute,
unpublished tabulations from the 2000 Medicare Current Beneficiary
Survey and Medicare Claims, 2005; published by the Alzheimer's
Association, Alzheimer's Disease Facts and Figures, 2007).
Cognitive decline can have profound implications for a person's
health and quality of life. It affects a person's ability to use words,
identify objects, make decisions, and communicate with loved ones.
Gradually, people experiencing severe cognitive decline may be unable
to care for themselves or to engage in necessary activities of daily
living or instrumental activities of daily living, such as preparing
meals or managing their finances. Cognitive decline may also limit
one's ability to effectively manage medications and existing medical
conditions. Adverse changes in cognitive abilities can make an
individual more vulnerable to malnutrition, improper use of
medications, injuries, and even abuse and other crimes.
The adverse effects of cognitive decline go well beyond those
suffering from it. Seven out of every ten people with Alzheimer's
disease live at home. Caregivers often find the task of caring for a
person with Alzheimer's disease to be physically exhausting and
emotionally challenging. The demands on caregivers adversely affect
their lives and eventually impact our economy when caregivers must take
time off from work, work part-time instead of full-time, take less
demanding jobs, opt for early retirement, or stop working altogether.
Because of these adjustments, Alzheimer's disease costs American
businesses billions of dollars each year--more than $36 billion in lost
productivity (absenteeism, productivity losses, and worker replacement
costs) plus nearly $25 billion for the businesses' share of coverage
for health and long-term care expenses (Koppel R. Alzheimer's disease:
the costs to U.S. businesses in 2002. Chicago, IL: Alzheimer's
Association; 2002.).
THE ROLE OF PUBLIC HEALTH
Public health's role in physical health is well defined. Thanks to
decades of multidisciplinary research, prevention efforts are now
applied to a variety of chronic conditions and their associated risk
factors. In the area of cognitive health, however, we have only
recently begun to delineate public health's roles and responsibilities.
Alzheimer's disease and other dementias are costly and
debilitating, and we anticipate the incidence of Alzheimer's disease
and other dementias will increase markedly as our population ages.
Recent scientific findings by the National Institutes of Health focus
on factors such as high blood pressure, diabetes and physical
inactivity associated with cognitive decline. According to the
Cognitive and Emotional Health Project report, a large number of
lifestyle and health behaviors may alter the risk for maintenance of
cognitive and emotional health.\3\ However, the report cautions that it
is not yet possible to develop individual prescriptions.
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\3\ Hendrie HC, Albert MS, Butters MS, Gao S, Knopman DS, Launer
LJ, et al. The NIH cognitive and emotional health project: report of
the critical evaluation study committee. Alzheimer's & Dementia
2006;2:12-32.
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Public health has an opportunity to build upon existing knowledge,
anticipated future breakthroughs, and the public's desire for
information. By embracing cognitive health as a priority issue, the
public health community with CDC's leadership can be mobilized to
study, identify, implement, and monitor effective interventions that
preserve this key component of health and well-being, and help to
maintain independence and quality of life.
COGNITIVE HEALTH: AN EMERGING PRIORITY AT CDC
CDC recognizes the vital role that physical, mental and cognitive
health play in shaping our overall well-being. We are committed to
ensuring that all people, especially those at risk for health
disparities, enjoy good health and the best possible quality of life at
every stage of life. For older adults, a primary goal is to ensure that
the years gained through increased life expectancy are healthy years
and to prevent or delay illness and functional decline. It might be
said that our goal is to help ensure Americans live a vibrant and
productive life throughout their aging years.
CDC takes a multi-faceted approach to improving cognitive health.
Some of the outcomes CDC has either achieved or is working to advance
include the following:
Last month we released The Healthy Brain Initiative: A
National Public Health Road Map to Maintaining Cognitive Health
(www.cdc.gov/aging/roadmap). This call to action proposes priority
actions to move cognitive health into the national public health arena.
The Road Map is a major accomplishment. Under shared leadership of the
CDC and the Alzheimer's Association, and in close collaboration with
the National Institutes of Health, the Administration on Aging and
others, we embarked on an intensive process to develop the Road Map.
Several cross-cutting areas of focus are recommended drawing on the
proven expertise and capacities of the public health community. These
include communicating the current state of science about cognitive
health to Americans; developing tracking measures to better understand
the public health burden of cognitive impairment; and delineating the
potential value of public health strategies known to be effective for
other health issues, such as physical activity, in maintaining
cognitive health and preventing cognitive decline.
CDC is bringing public health practice and research
communities together to move them forward on getting out current
scientific information about cognitive health. CDC is funding the
Healthy Aging Research Network, within its larger Prevention Research
Centers Program (PRC-HAN), to increase our understanding of the
public's, including caregivers and health care providers, needs and
perceptions about cognitive health. Assessing the public's needs and
how they think and talk about this issue is an important part in
addressing cognitive health.
CDC is excited to be at the forefront of national efforts, working
in collaboration with Federal and private sector partners, to advance
cognitive health. Cognitive health is a cross-cutting issue that
touches upon areas such as vascular risk factors, physical activity,
social engagement, and caregiving. It fits within CDC's healthy aging
agenda and older adult health goal to promote health at every stage of
life. It is aligned with CDC's commitment to increase the number of
older adults who live longer, high-quality, productive, and independent
lives. Our involvement with the Healthy Brain Initiative also is
aligned with CDC's strategy to create and disseminate the knowledge and
innovations people need to protect their health now and in the future.
CDC is known for monitoring changes in health status, translating
research into practice and providing high-quality health information.
Maintaining cognitive health and preventing cognitive decline is a
cross-cutting issue. CDC's activities to prevent cognitive decline
already touch on several promising areas, such as physical activity,
and managing diabetes and cardiovascular risk factors. However, our
work also extends to new areas, such as the benefits of social
engagement and caregiving concerns. Working within the framework set
out by the Road Map, CDC has identified several national public health
efforts we can best advance and support to safeguard Americans'
cognitive health. We hope to build upon our existing activities with
the Alzheimer's Association and other partners to put critical public
health elements in place to promote cognitive health and prevent
cognitive decline. As the science evolves, we hope to develop
community-based public health interventions designed to help Americans
maintain their cognitive health. And, as we proceed on this journey
together, we look forward to collaborating with our colleagues across
the Department of Health and Human Services to inform the Nation's
public health infrastructure about the science undergirding our
knowledge about cognitive health and promising interventions.
CLOSING SUMMARY
Thank you for the opportunity to speak on the issue of cognitive
health and the benefits of addressing cognitive health within the
public health arena. No less than cardiovascular disease, cancer or
diabetes, addressing cognitive impairment should be a critical public
health priority and deserves committed national public health action.
Promising research findings coupled with public health action in the
areas of epidemiology, surveillance and evidence-based interventions
can translate to a difference in our understanding of cognitive
decline, and our ability to address this issue in a positive way for
the benefit of all Americans. We at CDC appreciate your continued
commitment to efforts related to Alzheimer's disease and other
dementias, and we look forward to working with you and our national
partners in ensuring that cognitive health is addressed in an
aggressive manner commensurate with the fundamental role that it plays
in our overall health and quality of life. I would be happy to answer
any questions you might have.
Senator Mikulski. Dr. von Eschenbach, you've come to us
from FDA that has the job of standing sentry over our food
supply and our drugs to go into clinical practice and our
medical and biomedical products and devices. You come with an
incredible background and you were at NIH yourself, heading the
National Cancer Institute. And now, of course, you come with a
background in oncology. We'd like to hear, then, from you, how
you see FDA's role in dealing with the epidemic, at the same
time having the mandate. We ask you to do two things. We ask
you to move things as quickly as possible into clinical
practice but at the same time, including this committee, has
been very demanding in terms of the safety issues as well as
efficacy.
So tell us how you see we can deal with the epidemic, the
new thinking, how you work with the private sector.
STATEMENT OF ANDREW C. VON ESCHENBACH, M.D., COMMISSIONER OF
FOOD AND DRUGS, FOOD AND DRUG ADMINISTRATION, U.S. DEPARTMENT
OF HEALTH AND HUMAN SERVICES, ROCKVILLE, MD
Dr. von Eschenbach. Thank you very much, Senator and thank
you for framing it so well, but let me first thank you and
Senator Burr and Senator Isakson and other members of the
committee for convening this really extremely important
discussion. I'm joined today from the FDA by Dr. Bob Temple and
Susan Winkler, Rph, Esq., but it's a particular honor for me to
appear on the same panel with my colleagues from CDC and from
NIH.
Dr. Zerhouni, Dr. Gerberding and I have been working hard
to make our relationships productive and integrated so this is
not simply a ceremonial gathering. This is evidence of a
commitment on our part for close collaboration to be able to
accomplish progress in the diseases like Alzheimer's.
Every promising new drug, every diagnostic test, every
imaging technology that's designed to help Alzheimer's patients
must come through the FDA before it reaches those people. So
our responsibility is to help make sure that those products are
available and to determine that they are safe and effective. We
are doing this immersed in the 21st century revolution in
science and technology that I personally describe as the
molecular metamorphoses.
It's particularly important because it now provides us, as
you heard from Dr. Hodes, unique opportunities to understand
diseases like Alzheimer's at the genetic, molecular and
cellular level and therefore be able to make possible
extraordinary new opportunities, new interventions, new
solutions to prevent, treat and slow the progression of this
disease.
In that context, FDA--the FDA of the 21st century must be a
bridge and not a barrier to that new future. From the very
discovery of promising new therapies through their development
and ultimately to its delivery to Alzheimer's patients, FDA is
committed to be immersed in promoting and fulfilling our
promise to the American people.
We must be actively engaged at every step along that
continuum and we want to do that in a way to be an efficient
and effective pathway so that we're free of speed bumps and
potholes in our regulatory process. But as you pointed out,
also be sure that we have strong guard rails on that pathway
with guidances, regulations and standards that will also
protect the American people.
Central to our efforts in this regard to modernize the FDA
is the Critical Path Initiative, which is bringing the tools of
modern science and technology to the regulatory journey that
these medical products, these solutions must make from the
earliest stages of development to their use in patients. We,
among the Critical Path Initiatives, have many activities that
are being carried out in partnership with NIH and others,
particularly, for example, around the area of developing
biomarkers that can be used to determine the impact of a drug
on the amyloid plaque that is associated with Alzheimer's
disease or to use new clinical trial designs that will not
require 20 years for us to determine whether a new product can
help prevent this dreaded disease.
We are, in a sense, attempting to try to open the
floodgates of the development of products for Alzheimer's
disease and we will continue to move this process forward in
concert with and in collaboration not only with our partners
but with the community. Over the past year, I've personally met
with two prominent Alzheimer's disease patient advocacy
organizations, the Alzheimer's Association and the
organization, Accelerate New Treatments for Alzheimer's
disease. I share their concerns around the urgency of FDA's
ability to bring these new products to patients.
We are continuously, throughout FDA, remaining in contact
with these organizations and particularly to be able to
understand the opportunities that we must be addressing. We
also are engaged with the academic industry and particularly
seeing this as a problem in which we are all in this together:
industry, government, caregivers and the scientific community.
I just want to highlight a few of the important initiatives
that I think are tangible contributions to this overarching
strategic perspective. During fiscal year 2006, our Division of
Neurological Products and our Center for Drug Evaluation and
Research held 18 formal meetings with industry and this doesn't
include internal FDA meetings to discuss sponsors'
investigational new drug applications. To this date, the
Division has met with industry six times in an effort to help
facilitate their ability to develop and bring to the regulatory
process, successful drugs for Alzheimer's disease.
We need to also be able to leverage progress that's being
made in other neurologic diseases. For example, we are
conducting a planning meeting to help determine the best
designs for clinical trials for Parkinson's disease but we are
doing that in a way in which we expect to extrapolate those
results for our formal guidance that would be directed and
applicable to trials, clinical trials, in Alzheimer's.
We're working to improve our internal processes, our
standards, our processes for expediting review and we've
established within the FDA, an inter-agency neurological
working group so that we're focused across the agency on the
critically emerging problems that we're discussing today. This
group meets monthly, includes members from our Center for
Biologics Evaluation and Research, our Center for Drug
Evaluation and Research, our Center for Devices and Radiologic
Health, along with the Office of the Commissioner, Office of
Critical Path Programs, Office of Special Health Issues and
Office of Science and Health Coordination. This is an effort to
bring the full force of the FDA to bear on this critically
important problem.
We're also attempting to contribute to the underlying
understanding of this disease and the tools that we must apply
so that within the FDA's National Center for Toxicological
Research in Arkansas, we have two very specific Alzheimer's-
related projects underway. One is to develop a non-invasive
automated technology for assessing patients with Alzheimer's
disease so that we may be able to provide reliable and
objective measures to monitor the progression of the severity
of the disease and the impact of these innovations on that
progression. We see this as an invaluable tool that will spur
academic research in the pharmaceutical and biotechnology
industry in the development of these medical products.
We're also looking at a new histochemical test battery that
will enable us, as regulators, to assess the efficacy and
toxicity of potential drugs for Alzheimer's and this could help
us be able to streamline and improve the development of these
drugs to be able to bring them more reliably, more safely and
sooner to patients that are threatened by this degenerative
disease.
These are just a few examples of how we at the FDA want to
be a bridge and not a barrier to providing hope and expectation
for those with and those threatened by Alzheimer's disease for
a new future, a future in which they will not fear the
consequences of this terrible degenerative process.
[The prepared statement of Dr. von Eschenbach follows:]
Prepared Statement of Andrew C. von Eschenbach, M.D.
INTRODUCTION
Madam Chairman and members of the subcommittee, I am Dr. Andrew C.
von Eschenbach, Commissioner of Food and Drugs at the Food and Drug
Administration (FDA or the Agency). I would like to applaud the
subcommittee for holding this roundtable discussion to discuss Federal
initiatives to address the cruelly debilitating condition known as
Alzheimer's disease. FDA shares your commitment to vigorously
addressing Alzheimer's disease, and shares your hope that safe and
effective treatments for this condition will be approved in coming
years. It is a pleasure to be here today with my colleagues from the
Department of Health and Human Services, Dr. Julie Gerberding, Dr.
Elias Zerhouni, and Dr. Richard Hodes.
I very much appreciate the opportunity to join this discussion to
explain FDA's role as it applies to new products being developed for
treatment of Alzheimer's disease. Further, I will describe several
initiatives FDA is undertaking to transform the Agency in an effort to
meet the regulatory challenges arising from rapid advancements
occurring in all areas of medical research including Alzheimer's
disease, and several special initiatives underway at FDA that are
directed toward Alzheimer's disease.
In the two recent hearings on Alzheimer's disease before this
subcommittee you heard current statistics recently released by the
Alzheimer's Association including that this disease now afflicts one in
eight Americans over the age of 65 and some 47 percent of Americans
over the age of 85. At the present rate, the estimated 4.5 million
cases of Alzheimer's disease today can be expected to rise to around 16
million by 2050. With the aging of the baby boom generation over the
next several decades, without safe and effective treatments and
preventatives, a huge population of seniors stands to be robbed by this
disease of the enjoyment of their later years. In addition to the
burdens placed on patients and their families, insurance programs
surely will face overwhelming demands on their services and resources.
There is cause for some cautious optimism. You also heard of
exciting advancements in research on Alzheimer's disease such as
identification of amyloid peptide as a possible molecular cause of
Alzheimer's disease. Some researchers believe it is realistic to expect
that the progress of Alzheimer's disease can be slowed or halted by
products developed to affect the amyloid peptide. However, researchers
also have emphasized that this is a very complex disease that will need
to be approached from several different directions. A number of
promising new treatments in many areas are in the works; a few were
mentioned in your previous hearings as approaching the stage of
clinical trials.
As you may know, FDA is legally restricted from discussing any
individual products that already may be under review by the Agency.
This precludes me from being able to discuss specific unapproved
products in today's public forum. I can tell you, however, that
Alzheimer's and other neurological diseases are very active areas of
research and of work within the Agency. FDA reviewers interact
constantly with manufacturers and sponsors of prospective new products
(drugs, biologics, medical devices or combination products) to help
develop, and then to review, suitable clinical trials to test whether
their products are safe and effective. This is a very intricate and
time-consuming process. Our reviewers work with industry in all phases
of the development of a new product, both before and during clinical
trials, as requested by the sponsors. As always, FDA stands ready to
expeditiously review applications for any breakthrough products that
are presented to us.
FDA recognizes its dual role as evaluator of the safety and
effectiveness of new therapies and as the encourager and facilitator of
efforts to apply new scientific discoveries to patients who are in
need. FDA serves as a bridge to the future of successful new medical
product development. The Agency has a proud record over the past
hundred years of being the world's gold standard in medical product
regulation, but FDA cannot rest on its past and must come to grips with
the new realities of our regulatory responsibilities. Therefore, we
have embarked on a process of looking internally at transformations
that must occur within the Agency, and to identify opportunities to
collaborate with drug developers and other scientists on the discovery,
development, assessment and delivery of new treatments. I would like to
share some of these efforts with you.
THE CRITICAL PATH INITIATIVE
In today's world of health care and medicine, we are on the brink
of unprecedented advances in our ability to predict, diagnose, and
treat disease. Approximately 100 years ago, our ability to understand
disease moved from the macro level, where we were limited to what was
visible to the naked eye, to the micro level--when we gained a
microscopic view of disease at the cellular level. In the last decade
or two, we have been able to approach disease at the molecular level,
where we now can observe and understand disease as a process. As our
knowledge of genetic molecular mechanisms evolves and our understanding
improves, we will be uniquely positioned to develop interventions
against disease processes at the molecular level.
Yet a problem emerges. Despite an unprecedented increase in funding
for biomedical research, both in the private sector and through Federal
funding, this increased research has not translated into many new
medical products being available in the medical marketplace. There are
exceptions, of course, notably in the development of new treatments for
cancer and AIDS, and some inflammatory diseases. Close to 9 in 10
pharmaceutical products in phase 1 clinical testing are never approved
for marketing, and half of all drugs that enter phase 3 clinical trials
are never approved. In an effort to help expedite and simplify the
medical product development process, in 2004, FDA advanced the notion
of focusing on the critical path which medical products must travel
from the earliest stages of development to their use in patients. The
Critical Path Initiative is FDA's effort to stimulate and facilitate a
national effort to modernize the sciences through which FDA-regulated
products are developed, evaluated, and manufactured.
FDA is working with the academic community, the public, the
pharmaceutical industry, and other Federal health agencies (e.g., the
National Institutes of Health (NIH), the Centers for Medicare &
Medicaid Services, and the Department of Veterans Affairs) to modernize
and transform the development and use of medicines. After intensive
consultation with many stakeholders, last year the Agency published our
Critical Path Opportunities Report, which details 76 specific
scientific projects with great promise for smoothing the path from lab
to bedside. Last December, we followed up by announcing more than 40
very promising scientific projects that we have helped launch. These
projects support the development and approval of new treatments for
conditions such as Alzheimer's, diabetes, cancer, and chronic pain. For
example, improved predictive and evaluative tools that help identify
candidate products that are likely to fail early in the development
process will enable the investment of resources in those products most
likely to succeed. Streamlining clinical trials--making them more
efficient and safer--will help move new therapies to patients sooner
while protecting clinical trial participants. Among many other
activities, the Initiative also supports the implementation of
information technologies that will enable us to tap into existing data
repositories to expand research into disease areas and improve
efficiencies. The Critical Path Initiative is a long-term, national
effort that is helping to ensure that promising new therapies in the
development pipeline today will reach the patients who need them sooner
and at less cost. The projects under way today as part of the Critical
Path Initiative will improve treatment, improve safety, and improve
patient access.
Another example of the Critical Path Initiative is The Biomarkers
Consortium launched in October 2006. This is a public-private
biomedical partnership established by FDA and many colleagues in the
scientific community that is supported by the Foundation for the
National Institutes of Health. The Biomarkers Consortium strives to
accelerate the delivery of successful new diagnostic approaches and
therapies to prevent, detect early, diagnose, and treat a wide variety
of diseases. Among other efforts, the Consortium seeks to identify
biomarkers and develop tests to determine whether a drug is appropriate
for an individual patient. It also is working to find ``markers'' that
will show whether a drug is having the right effect in the patient. For
example, researchers have found that patients whose tumors have
specific genetic mutations or surface properties respond to particular
treatments. This mutation then serves as a ``marker'' to identify the
patients who are best treated with these medications.
Over time, similar discoveries related to other tumors, other
diseases and conditions, and other drugs will yield a major public
health impact--and that is the point of the Critical Path Initiative.
Working with all stakeholders, the Critical Path goal is to get the
right medicine to the right patient, in the right dose, and at the
right time. It will make innovative medical products available sooner,
increase our ability to monitor their safe use once they have reached
the medical market, provide for personalized diagnosis and treatment,
and introduce great efficiencies while reducing risk.
TWO EXAMPLES OF ALZHEIMER'S RESEARCH WITHIN THE AGENCY
Now, I would like to talk about two Alzheimer's-specific projects
that FDA has undertaken. First, FDA scientists from our National Center
for Toxicological Research (NCTR) collaborated recently with scientists
at the University of Arkansas for Medical Sciences, the University of
Arkansas at Little Rock, and the Central Arkansas Veteran's Health Care
System to conduct an automated cognitive assessment of persons with and
without Alzheimer's disease. The study investigated performance on
metrics for a variety of behavioral test tasks that measure timing
perception ability, short-term memory, and learning ability using an
automated system called the NCTR Operant Test Battery (OTB). The study
outcome indicated that the persons with Alzheimer's disease were
significantly less accurate in the time perception and short-term
memory tasks and were rarely responsive in the learning task. The OTB
is a non-invasive, automated, non-threatening assessment technology
that can differentiate between normal controls and persons with
Alzheimer's disease. This automated assessment instrument has the
potential to provide reliable, objective measures that can be used to
monitor the progression and severity of the disease process and assess
effectiveness of interventions over time. A report on this study is in
preparation.
Currently, FDA/NCTR scientists are initiating a study to develop a
histochemical test battery for assessing the efficacy and toxicity of
putative anti-Alzheimer's disease drugs, the safety of which will need
to be evaluated in the FDA regulatory review process. There are two
broad categories of anti-Alzheimer's drugs: those that provide
symptomatic relief and those designed to prevent or slow the
degenerative process. So far, those in the first category have been
developed and shown effective, and are approved for use by FDA. Those
designed to cure or reverse the disease process are in early
development or, in some cases, in clinical trials. The development of a
therapeutic histochemical test battery has the potential to help
identify earlier and more reliably drugs that might slow the
degenerative process. This study is scheduled to begin later this
fiscal year.
THE PATIENT REPRESENTATIVE AND CONSULTANT PROGRAMS
FDA also has engaged with the Alzheimer's disease patient advocacy
community regarding that community's involvement in FDA decisionmaking
during development of new medical products. Through FDA's Patient
Representative Program, they will be able to participate in FDA
advisory committee meetings, advising the Agency on marketing approval
decisions and in response to issues arising with marketed products, as
well as help advise the Agency about the development of investigational
drugs. Their involvement is important to FDA's capacity to make
informed regulatory decisions that are sensitive to the needs and
preferences of those affected by this disease.
This expansion of FDA's programs has involved considerable
challenge, as FDA has negotiated with Alzheimer's disease advocacy
organizations regarding the role of Alzheimer's disease patients
themselves. FDA considers patient involvement important, since patients
with a given disease are generally best able to speak for others with
that disease. Involvement of patients with Alzheimer's disease is also
an important priority to the Alzheimer's disease advocacy community.
However, participation of patients with Alzheimer's disease is
problematic because of diminished intellectual function that is a
primary manifestation of this disease. This challenge is exacerbated by
Alzheimer's disease patients' deterioration in intellectual function
over time.
After extensive negotiation, we have agreed to recruit advocates
from the Alzheimer's community, including couples consisting of a
patient with early-stage disease and his or her caregiver, both of whom
have a background appropriate for involvement as FDA patient advocates.
The caregiver will serve as the primary spokesperson for the couple,
but both parties will have access to materials for review, will be able
to review and discuss those materials prior to their engagement with
FDA, and will have the opportunity to participate. When the patient is
no longer able to participate, the caregiver will continue to serve
with FDA. FDA and the Alzheimer's community agree that this approach
involves challenges, but both parties are willing to work to maximize
involvement of patients.
THE FDA INTRA-AGENCY NEUROLOGY WORKING GROUP
Next, I would like to mention FDA's Intra-Agency Neurology Working
Group. Neurology products regulated by FDA, comprised of drugs,
devices, biologics, and combination products, are a diverse group of
products aimed at advancing patient care in a number of disease areas
for which the unmet therapeutic need is great. Some diseases affect a
large number of patients, such as Alzheimer's disease and Parkinson's
disease, while others affect smaller numbers of patients. In either
case, the consequences can be devastating for patients and their
families.
FDA's goal is to improve communication about neurological disease
across the Agency among the various groups charged with regulating
these products. To accomplish this end, FDA has established a Working
Group to serve as a forum for information exchange on leading-edge
developments, enable sharing of technical and regulatory expertise, and
provide for greater consistency of review standards and processes
across the Agency. Further, we are expanding patient advocate
involvement in FDA neurological disease-related review and
decisionmaking to include Parkinson's disease, Alzheimer's disease, and
other neurological diseases as Agency resources allow.
Meetings occur monthly and are chaired by Dr. Celia Witten,
Director, Office of Cellular, Tissue, and Gene Therapy in our Center
for Biologics Research and Evaluation (CBER), and Dr. Robert Temple,
Director, Office of Drug Evaluation I and Director of the Office of
Medical Policy in our Center for Drug Evaluation and Research (CDER).
Other members include Dr. Russell Katz, Director of the Division of
Neurology Products (CDER), and supervisors, reviewers, and project
managers from CDER, CBER, and our Center for Devices and Radiological
Health. Also included are staff from the Office of the Commissioner,
including the Office of Critical Path Programs, the Office of Special
Health Issues (OSHI) and the Office of Science Health Coordination.
Standing agenda items include policy development (guidance, workshops,
and advisory committee meetings), opportunities for Critical Path
projects, significant review projects (major investigational/marketing
applications under review, marketing approvals, studies of interest,
etc.) upcoming neurology-
related meetings and patient advocate involvement, and OSHI updates.
ADDITIONAL FDA ALZHEIMER'S-RELATED ACTIVITIES
The Agency is engaged in a number of additional Alzheimer's-related
activities. For instance, FDA is helping with a study called the
Alzheimer's Disease Neuroimaging Initiative. This is a 5-year public-
private initiative involving industry, academia and the NIH. The goal
of this study is to obtain standardized MRI, biochemical, and clinical
data over several years in prospectively followed groups of normal
elderly patients with mild cognitive impairment, considered the very
early stages of Alzheimer's disease, and patients with diagnosed
Alzheimer's disease. We anticipate that this study will help in the use
of some of these measures in future clinical studies to expedite the
development and approval of drugs to treat patients with Alzheimer's
disease, especially in its very earliest stages. A particularly
exciting and important aspect of this study is that the data are
available to scientists all over the world in real time as the data are
acquired and entered into the database.
Additionally, FDA has a productive and close working relationship
with the Alzheimer's disease advocacy community. For example, FDA has
worked closely for many years with the Alzheimer's Association on
scientific, technical, and advocacy issues. Their counsel and direct
assistance to FDA have been invaluable as we have worked to improve our
regulation of Alzheimer's disease treatments and to expand patient
involvement in FDA decisionmaking.
FDA recently met with, and remains in contact with, the Accelerate
Cure/Treatments for Alzheimer's Disease (ACT-AD) Coalition. They are
concerned that the Agency retains a strong focus on drug development
for Alzheimer's disease. The Agency works and keeps in contact with
these organizations through OSHI. I certainly encourage this important
exchange of ideas with advocacy groups.
Development of drugs with an effect on disease progression is the
most critical need in Alzheimer's disease, as it is with other
progressive neurological diseases. FDA is planning a future public
meeting to discuss design of clinical trials and how to design studies
to determine whether or not a drug for Parkinson's disease has an
impact on the underlying cause of the disease and not just the symptoms
of the disease. It is expected that the designs useful in Parkinson's
disease should be equally applicable to drugs for Alzheimer's disease.
In addition, FDA is organizing an upcoming meeting with
neurological disease organizations involved in advocacy and medical
research. This meeting will involve discussion of scientific,
technical, and advocacy issues related to their and FDA's roles in
development of important new treatments for serious neurological
diseases, including Alzheimer's disease.
CURRENTLY APPROVED DRUGS FOR ALZHEIMER'S TREATMENT
Finally, I want to make sure that I mention to the committee that
there currently are five drugs approved for the treatment of
Alzheimer's disease: Cognex (tacrine); Exelon (rivastigmine); Razadyne
(galantamine); Aricept (donepezil); and Namenda (memantine). All except
Namenda are approved for the treatment of mild to moderate Alzheimer's
disease. In addition, Aricept also was approved recently for severe
Alzheimer's disease. Exelon was approved on July 6, 2007, in the form
of a transdermal patch, which reduces gastrointestinal side effects
compared to the oral form of the medication. All of these drugs except
Namenda act by increasing brain levels of acetylcholine, a
neurotransmitter that is abnormally low in patients with Alzheimer's
disease. Nerve pathways in the brain that are thought to be involved in
memory and cognition, that ``use'' acetylcholine as a neurotransmitter,
degenerate in patients with Alzheimer's disease.
Namenda is approved for the treatment of moderate to severe
Alzheimer's disease only. It works differently than the other approved
drugs. It interacts with a receptor that is thought to be involved in
preventing the death of certain cells in the brains of patients with
Alzheimer's disease. However, the drug has never been shown to prevent
or slow the underlying nerve degeneration in these patients, nor have
any of the other approved drugs been shown to do anything other than
treat the symptoms of Alzheimer's disease.
CONCLUSION
We await, together with the rest of the world, for new drugs that
may some day be able to treat the underlying cause of this insidious
disease as well as other neurological diseases, not just the symptoms.
We are very encouraged by the progress being made in the scientific
community and pharmaceutical industry on products you heard about in
testimony in the previous two hearings. As indicated earlier, FDA
stands ready to facilitate any breakthrough product applications that
are submitted to the Agency for review.
This concludes my formal statement. I will be pleased to respond to
any questions from the subcommittee.
Senator Mikulski. Well, thank you very much, Dr. von
Eschenbach. I think already--did you want to ask a couple of
questions and I'd be happy--but I just wanted to say first of
all, it's a very impressive group but it's impressive already
at the level of coordination and communication that's going on.
So I said, this is not to be a roundtable. Our friend, Senator
Isakson, has to leave and I didn't know if you had a couple of
questions you'd like to pose and the way we see it, is we're
just going to kind of jump in and even though you might pose it
to someone, if somebody else has got something to add, we don't
have to be starchy and choreographed here.
Opening Statement of Senator Isakson
Senator Isakson. Well, thank you, Madam Chairman. I am
going to have to leave because I have another Georgia company
waiting in the office but anytime Dr. Gerberding shows up, I
show up because I am her biggest cheerleader. She's done a
marvelous job for CDC and I'm very grateful for the many
contributions that she makes.
I won't ask a question. I'll just make a comment. The
reason I have a passionate interest in this, I lost my mother
to Alzheimer's. But over the years, I've had some experiences
that illustrate to me how important it is for us to get into
the surveillance business that you talk about in your pathway
and look for some answers because I've had one of my doctor's
wife, at the age of 46, who was diagnosed with Alzheimer's,
Governor Carol Campbell, a great governor of South Carolina in
his fifties was diagnosed and died in 3 years and in my church.
I have two members whose wives--both of their wives have had
Alzheimer's for a significant period of time and it's apparent
in the last decade that some pharmaceutical therapies and other
treatments are beginning to work to prolong and improve the
quality of life of those individuals with it but it's a must--
and I agree with what Dr. Gerberding said that everybody fears
physical impairments but everybody is more fearful of cognitive
impairment.
So I appreciate the Chairperson's diligence on this effort
and her real passion in seeing to it that we raise the
eligibility and as I told her a few months ago, I'm here to be
a soldier in that army and I'm grateful to you all for what you
do.
Senator Mikulski. Thank you very much, Senator. At the end
of this conversation, we will begin to meet on getting ready
for our markup on our Alzheimer's Breakthrough bill,
particularly the research component. It would be the goal of
Senator Burr and myself to have this marked up either by the
end of July or certainly in September and move it on through to
get it done. So we've heard from the Alzheimer's Association,
research community and we're going to have more conversation
with you.
Let me jump in with my question. Of course, we agree with
Dr. Zerhouni that intervention, even before physical or mental
manifestations of anything from heart disease--you don't want
to wait for that out-of-breath shooting pain or for women,
fatigue and other symptoms. And we'll be talking about that.
But one of the things that I'm interested in is how we can now
take basic research findings that we already know that might
not need a pharmaceutical intervention and move it into
clinical practice, better diagnosis because we've heard that in
many instances, it's misdiagnosed as depression early on or
when people start that 36-hour day, the agitated behavior where
other medications are prescribed.
That's one--use information we already have, say at NIH or
the private nonprofit community and then how does that get
translated into clinical practice or what we fund. Let me go to
something else, which is what seems to be emerging from the
research is the low-tech solution that what is needed of good
diet, exercise of both the body and the mind, is very good. If
you have heart disease, diabetes--any propensity that you might
have that is starting back here, though you might not be able
to beat change, you can delay the consequences of genes and so
on and my question then is, if that's so and that's thoroughly
been validated and I think it has, then how does it get out to
both clinical practice and then even to entities like the
Office on Aging? What does all that mean while we're working on
even more sophisticated and more precise breakthroughs? Do any
of you want to comment on translating research into clinical
practice? I just throw out diagnosis and I just put that out
for discussion, the techniques we now know for the management
of any chronic illness seems to have a major role also or
significant role in preventing cognitive decline, whether it's
Alzheimer's or something else. Do any of you want to comment on
that?
Dr. Hodes. I think you posed a very critical question about
our translation from scientific findings from what we know into
practice and let me try to give two examples because I think
it's important that we recognize our obligation to do the most
we can with what we know.
Now let me first take one of the more precise examples of
an attempt to translate genetic and biological information at
the interventions and this comes from the original observations
100 years ago, when the initial patient with Alzheimer's
disease, by the professor of the same name, identified plaques
and tangles in the brain and we've seen over the past years,
his remarkable identification of the biochemical nature of
these plaques and tangles, the genes that encode the products.
This has led, in turn, to the ability to generate animal models
that reproduce much of the lesion, the memory defect of
Alzheimer's disease caused by introducing a particular gene
product. So there is very strong evidence that it is quite
possible that a particular molecular lesion is responsible for
Alzheimer's disease.
This is now leading to clinical trials. The only way to
completely verify the ability to intervene in this pathway and
have an effect--the trials are not simple as with any drug
trials but they are attempts to modify the effect of the
enzymes that cause the amyloid plaque or as we've heard,
immunization treatments to try to prevent or reverse the
accumulation of amyloid plague.
So this is an example of translating the most basic
molecular level through very rigorous levels of evidence to
establish whether or not an intervention, pharmacological,
immunological, have the desired impact and this is one
important pathway to pursue. It's important that our basic
science from institutions like NIH are translated to both
private sector enterprise and academic enterprise and
ultimately to the FDA to deal with final demonstration of
efficacy.
There is another pathway and one that you've eluded to that
deals with evidence or associations of certain lifestyle
factors and risk factors with Alzheimer's disease. So as you've
noted, there is strong epidemiologic data that indicate that
individuals who have many of the risk factors for
cardiovascular disease, diabetes, high levels of homocysteine
are more likely to have Alzheimer's disease. Therefore, it is
important that we carry out rigorous clinical trials to see
whether the interventions for those treatments will or will not
have effect on Alzheimer's disease.
Now, do we need to wait until we have that information
before recommending that people follow lifestyle interventions
such as diet, control of blood sugar in individuals with
diabetes, diets that are demonstrated to protect against
cardiovascular disease--of course not. So this is a case in
which we don't have the highest level of evidence to show these
interventions will, without doubt, from randomized clinical
trials, prevent Alzheimer's disease. We know enough to
recommend to the public that in terms of general, successful
aging in health, these are strong measures that should be
translated while at the same time, I would suggest we pursue
the rigorous science to see just how they affect variables such
as cognitive function.
I think the same is true for----
Senator Mikulski. It wouldn't hurt, would it?
Dr. Hodes. We certainly think it wouldn't help. It's been
demonstrated that these interventions are helpful for many
other aspects.
Senator Mikulski. Well, let me tell you when I first heard
about this and Dr. Zerhouni, you'll enjoy this. Senator Burr,
you might want to come with me. The National Institutes of
Aging is the one campus called Bayview at Johns Hopkins but
it's not in the main Broadway campus, which is like the mother
ship, contiguous to a neighborhood called Greek Town. Now,
Greek Town is where a large number of Greek immigrants settled
and oh gosh, they have food that is both the Mediterranean
diet, which we're supposed to follow but then they've got the
fried calamari and they have the baklava--you get it?
Dr. Zerhouni. You tell me where to eat and I'll go.
Senator Mikulski. And I'll get it for you. So I went to
visit then, that old creaking building that I know we're
replacing, but one of the first things that we heard was the
research in animals that really, the reduction in calories, the
improvement of exercise enables, at least it seemed to have a
positive impact. But what we also know is diabetes is a factor,
maybe. That this is a preventive act that does no harm, which
as all of you have taken that oath that the first thing is, we
could do things that do no harm. So Dr. Gerberding, what you do
think about that? Should we now, as a major public policy, take
what you're saying in the Healthy Brain Initiative but really,
what we already know for heart-smart, we could really be
troubadouring and promulgating. Do you have a reaction to this
and what you already know, knowing that we could always
validate more? And also then, what is CDC doing about this, say
in conjunction with the Office on Aging that funds every senior
center in America.
Dr. Gerberding. My reaction is enthusiasm in a short word.
I think we've got to set a stage to get this ball rolling and
one of the remarkable things that I observed on the times that
I was participating in some of the Medicare sign-up events or
some of the Welcome to Medicare, get your prevention screening
activities going on at the grass roots level, is how extensive
the network of support for seniors really is in our communities
because of the Agency on Aging and HERS and others and many,
many not private and other organizations. We have an extensive
network of community support in many communities and even
reaching into those populations that are hard to reach and have
the worst health disparities. But that network is not aware
that this is a critical strategy for protecting brain health
and I think the concept of social marketing, getting out to the
grass roots level and really informing people that it's not
only good to do these health promotion activities because they
are heart healthy. Some aspects of them are highly likely to
preserve mental functioning and as the database for that grows,
it will be able to give us stronger scientific basis for that.
So the first thing is to get the word out into the
community to the affected people but also that incredible
hidden network of support that already exists and mobilize it
to start really adding this to the perspective.
Senator Mikulski. Is that what CDC does and are you meeting
with the Office on Aging to do that?
Dr. Gerberding. Absolutely. And I think we did not have
these strong ties, admittedly in our Department but we have
come together in many different ways to support some of the
modernization of Medicare activities and we've discovered how
much leverage we actually have within HHS. I mean, Medicare
pays $91 billion a year for Alzheimer's disease. That's a
tremendous investment and we ought to be able to work with that
kind of resource and do more to help people prevent this in the
first place. But the other piece of this that we can't forget
is that clinicians also play a very important role and I do
think we need to be more aggressive about clinician education.
You've described in your written testimony, some
centralization of testing for Alzheimer's and cognitive
dysfunction so that we make a more accurate and early diagnosis
in those patients that can benefit from drug treatments, get
access to them but also it helps us understand the relationship
between cognition and capacity to engage in physical exercise
and the other Heart Healthy activities.
The tragedy here is as your cognitive function declines,
your ability to take your medications and to maintain your
mobility and control your blood sugar declines concomitantly so
you get into a vicious cycle of deterioration.
Senator Mikulski. Exactly.
Dr. Gerberding. I think we can do a lot more at the
clinical interface to prevent that deterioration.
Senator Mikulski. Well, I know Dr. von Eschenbach wants to
talk. I'll turn to Senator Burr but as we now get ready for our
markup, would you have your team meet with us to see how, as
part of our Alzheimer's Breakthrough, where we move to increase
funding for research, we look at how we can also more
effectively involve the role of CDC exactly in this
coordination in kind of moving out what we do know.
That if nothing else, how it's managed, the chronic illness
that Dr. Zerhouni said, you said, 75 percent of those people
over 55 consulting a clinician is for the consequence of a
chronic condition, not an acute episode or a fall or an
orthopedic injury or anything like that. So we want to come
back to you. Dr. von Eschenbach, did you want to say something?
Dr. von Eschenbach. With your permission, I'd just like to
amplify on two points I made in my statement, which go along
with the comments that have already been made. I indicated this
fact that today, we're in the midst of this molecular
metamorphosis. I also indicated that we're all in this together
and I think that bodes very well for tomorrow.
First of all, one of the implications of this tremendous
progress in biomedical research is the fact that as Dr.
Zerhouni alluded to, health care will be personalized, much
more predictive, pre-emptive and more participatory. And the
implications of those four P's for tomorrow is that first of
all, one of the things that's going to go a long way for us
having these public health interventions is to be able to
define populations at risk and to do that in a way that we can
really hone in on where these targeted interventions have to
occur that are going to be much more preventative and we'll
know that they'll be predictive because we know the evidence of
their outcomes.
At the same time, when we look at what's happening today
with information technologies and communications, we're seeing
health care become much more participatory. Faces no longer are
just passive recipients but actively participating in their
care and we now have the tools of communication and interaction
that enable us to help continuously guide patients in terms of
interventions that they should be carrying out day by day and
that's where agencies and organizations like the Alzheimer's
Associations have alluded to and others, like AARP, have a real
role in continuing the impact of these interventions at the
public health or community level and to do that in a way that
mobilizes and moves us to a better level of health.
I think it's comprehensive, it's integrated but I don't--
and I think the tools are going to enable us to do it far more
effectively tomorrow than we could do it yesterday.
Senator Burr. Thank you, Madam Chairman. I was struck, as I
listened to Dr. von Eschenbach, that we have a tendency to
focus on specific diseases and it just struck me with some of
the things you were saying, Andy, that we have a health care
delivery system designed in America not to fully engage us in
prevention and wellness and not really in disease management
unless someone is triggered from a quality of life standard to
do it.
And I would say to my good Chairman, maybe it's an area
that we can explore. I'm sure the answer to this is in the
challenge of how do you continue to see a population of a
country increase at the rate we are, while we devote 16\1/2\
percent of the GDP to health care and not be influenced by
other models around the country where they say, ``well, we do
it so much cheaper'' and the reality is that we can look here
today and as Dr. Zerhouni said, in X number of years that 5
million individuals with Alzheimer's are going to be 16 million
with Alzheimer's and there's full agreement at the research
table that the answer here is, we have to get ahead of the
curve. We have to be preventive. We have to be predictive.
We have to be willing to personalize and that's a
tremendous goal that NIH is under and it puts tremendous
strains on you from a standpoint of the agency at the end
that's going to be trying to approve therapeutics and vaccines
that are trying to keep somebody from getting the disease. What
a tremendous step we've made.
Dr. Hodes, today, how is the typical patient with
Alzheimer's diagnosed? What is it that triggers that person to
go in and say, ``boy, I think I got it.'' Or that family
member--who is it that initiates that and what process do they
go through?
Dr. Hodes. I think the simple answer is that it's very
heterogeneous and very variable. With a spectrum from
individuals who are very sophisticated, families are very
perspective and connected to a medical care system so that at
the early appearance of changes in behavior, including changes
in memory, they turn to physicians who are informed and
capable.
All too sadly, though, a large percentage of our population
is unfamiliar with the concept of these changes or anything
more than a part of aging and they are accepted as such and
diagnosis is, therefore, delayed. It isn't so many years ago
that everyone accepted dementia as an accompaniment of aging
and so we're at a point of transition where I think the best
informed and we need to make all of Americans better informed,
are tuned to seeking medical attention.
Once having come to medical attention, to a physician or
care provider, in the best of settings, estimates are that
approximately 90 percent accuracy in diagnosing Alzheimer's
disease is the theme. This is what we see in the best of hands
and far less accurate in others. So here, our commitment is to
try to identify the psychological test and our imaging tests
that can continue to refine a standard strategy for diagnosis
that will allow all of the care providers around this country
to be more astute in making diagnoses.
The impetus for making diagnosis is, of course, an
important issue. What is the motivation? Right now, a great
deal of the motivation is to rule out other causes of dementia
that are clearly treatable and reversible and one of the
greatest tragedies would be to be missing one of those. If
Alzheimer's disease is diagnosed and diagnosed early, of
course, there are real advantages to the individual and the
family in terms of planning and understanding prognosis and
finding those treatments, which are able to modify the course
of the disease.
But we have to concede that those treatments, those
interventions are currently of limited effectiveness and
effective for a limited period of time so that the motivation
to identify disease early, to come to diagnosis and to treat,
is going to become more critically important as we identify and
communicate interventions that make a difference.
Senator Burr. Well, we probably all agree that the first
interventions are probably going to be therapies that
potentially either slow or stop the progression of disease,
therefore the earlier we can detect, the better off the quality
of life and the outcome is.
Dr. Hodes. I should maybe just comment that while we have
great hopes and need for much more improved interventions, it
was just in the past months that there was a statistical
significance from a clinical study showing that one agent,
Donepezil, was in fact able to reduce the risk of moving from
mild cognitive impairment to a diagnosis of Alzheimer's
disease. It was a limited effect. It occurred only over the
first year of the study in most individuals but I think it
provides the first prototype, if you will, of an intervention
that can actually prevent the onset of disease.
I should also reinforce what's been said by my colleagues
about the importance in the area of public education, of
organizations that are in the grass roots. The organizations
prominently including the Alzheimer's Association, with whom we
have great interactions, not only in the planning of research
agendas but in the grass roots contact with individuals who are
affected in their families, important to providing and
communicating information, to recruiting individuals interested
in participating in clinical studies, which I need to stress,
is very important to progress so that all of the Federal
agencies, private sector organizations need to work together to
inform the public so they can both understand early signs, seek
diagnosis and then participate with us in the research that is
necessary to come to better means of intervention.
Senator Mikulski. I just want to come back to Senator
Burr's point about diagnosis. My father died of the
consequences of this, but these early signs--no one was quite
sure what it meant and this is when we had access at Johns
Hopkins, to a geriatric evaluation program, where a
geriatrician, someone skilled in the diseases or effects of
aging, could evaluate, what is the medications Dad was taking
for some other things, where the synergistic effect affected
his cognitive ability? Was it that he needed that shot of
Vitamin B-12, which we all hoped he needed, et cetera.
Well, unfortunately, it wasn't that but it could have been
that. And isn't this where, really, there needs to be some type
of really overall assessment? But do you feel that also, there
needs to be more of the specialized centers where a primary
care physician to validate what they suspect would occur? Or do
you feel that you can develop these--I don't want to say check,
but prototypes for at least the primary care people to make
some type of diagnosis?
That's not a catch-22 but it all goes to what should be
supporting here, one of which is accurate diagnosis even though
we might not have some magic bullet now. There are tools
available.
Dr. Zerhouni. I'd like to, if I may, really stress the
point you just made and that is, if you look on the forecast
basis, on how many geriatricians are going to be available to
really take care of an age population, what you find, in fact,
is that the number of geriatricians is not growing. It's
actually flat or decreasing in terms of the number of people
who graduate to study the diseases of old age.
So I think if you were from the 50,000-foot view before we
go to Alzheimer's, we have a fundamental issue in orientation
of resources toward creating the human capitol needed to take
care of this population as we go forward. There will be a
deficit in healthcare providers at all levels. It will be care
providers at home, care providers at the intermediate levels of
care.
So it's clear that when you really look at the total
system, we have an issue and we need to really work together on
finding ways of preventing the loss of the talent.
The other is that Alzheimer's disease today is a diagnosis
of elimination. You try to eliminate every possible potential
causes of cognitive deficit before you can make this diagnosis
because it is only diagnosable at this point through a biopsy
and we're not going to perform biopsies on live individuals,
biopsies of the brain.
So one of the things that need to be done is more
standardization of the diagnostic tests, an educational program
for centers to diffuse around them because we're not going to
be able to do it just with geriatricians. So we're going to
have to educate, at a very fast pace, not only in terms of the
prevention activities that Dr. Gerberding was talking about but
just pure clinical medicine for family doctors, internal
medicine doctors, a little bit of what we did for heart
attacks.
I mean, it was clear they didn't have enough cardiologists
to take care of heart attacks so you had to really diffuse the
knowledge way beyond the specialists. I think if you really
think about it, Senator, what you have to have--you have to
have a systems approach to the disease, from the first point of
contact, the loss of cognitive function, mood disorders,
wandering, losing your keys, losing the address of your house,
knowing how to go back, all these signs are overlapping with
many other conditions. So you have to eliminate it but at the
end, we as scientists, have to agree on a standard set of
parameters and tests to develop sets that are more objective.
There is no blood test today like there is for diabetes, for
Alzheimer's and we need to really come up with something, some
answers.
We've funded very innovative research at the NIH. We funded
nano-medicine, to pioneer, to in fact tell us whether he could
detect the very first signs of Alzheimer's disease in the fluid
that is within the brain, what we call the CSF, the cerebral
spinal fluid. And for the first time, we had a positive result
so there is hope to be able to do that on an objective basis.
My message here is this: if you look at any one point and
try to improve that, you're not going to get to your goal. In
other words, fighting Alzheimer's disease is only as strong as
the weakest link in the chain of research, intervention,
prevention, payment systems--how do you cover that? The
workforce planning, how many healthcare providers do you need?
This is truly, I think, the challenge that we have.
We have tried to educate, from our standpoint, we're just
releasing today the progress report on the research, on the
Discovery Pathways for Alzheimer's Disease and I want to
commend the National Institute of Aging and all our sister
agencies participating in this but this, in fact, is the
message that you will not solve this problem with a one magic
bullet approach.
Senator Burr. I'm sure Senator Mikulski agrees with me that
we really need each of you to pledge to work with us on this
legislation. There's only one way to get a perfect bill and
that's to make sure that all the stakeholders are on board at
the beginning of the process rather than to shoot at a bill
that we think is a pretty good product and I hope you'll do
that.
I remember years ago, Dr. Zerhouni, among the--almost the
completion of the mapping of the human genome. I was at SAS
Corporation in North Carolina, the largest privately owned
software company in the world and they envisioned at the time
that when they got the final genome mapping that they would be
able to go in and write a computer program that could then take
all of the known drugs and things that we had and could
potentially test them on what they had learned. How far are we
from that?
Dr. Zerhouni. We've made tremendous progress. I have to
tell you that over the past 3 years--when I became NIH
Director, I can recount the story about the fact that the human
genome had been completed. We, in diabetes, we knew one gene,
suspected gene. This was the effect of 30 years of work and it
was p-parg gamma as an enzyme and that's what we knew. Since
then, just this year, we found 10 very, very strong candidates
to understand at the genetic level, what makes a person
diabetic and why is it that they become diabetic, very, very
early in their natural history.
If you look at all of the progress that has been made
because of the biotech advances and the technologies today, we
have a project and it's called pharmacogenetics. It started
about 4 years ago and we have over 400 discoveries that show
why you or I would respond differently to a drug. The next step
is what we call the Gene Environment Initiative, which we
launched this year, where we're going to find the common
genetic traits of the 10 most common diseases, including
Alzheimer's, actually, which is also being researched.
We're very close to this. We have to accelerate our
research there. The opportunities are enormous. This is the
basis, actually, of this personalized medicine idea that you
and I, even though our DNA is only different by .1 percent, we
can react to the same treatment in completely different ways.
To know that ahead of time is very important.
Let me give you a very specific example. Today, we use
cholesterol lowering drugs, statins--Lipitor and Zocor on
millions of people but we know from the epidemiology that only
10 maybe, 10 percent of these people would ever develop a heart
attack or cardiovascular disease. Yet we give it to a hundred
percent of the people.
Wouldn't it be great if I had a signature that told me I am
part of the 10 percent that's going to get it and I need that
drug and you're part of the 90 percent that do not need to have
that drug. So you can see the impact on the cost of health
care, the precision with which we will treat people--all of
this is related to the advances of the past 2 years.
Senator Burr. Let me ask, I'm sure somebody has put
together information that's more global in scope for
Alzheimer's. The percentage of the American people that are
affected by Alzheimer's, is the percentage consistent with the
percentage of other countries in the world?
Senator Mikulski. Good point. Interesting.
Dr. Zerhouni. That's a good question. I actually will defer
to my colleague here.
Dr. Hodes. Well, there's incomplete information but enough
to be responsive. That is, I don't think that we have
comparable information on the prevalence of Alzheimer's by
similar standards in so many countries that we can answer that
with precision. But we do have information from very specific
studies that have, for example, compared the risk of
Alzheimer's disease in particular populations, one versus the
other. For example, in the population of individuals still
residing in Nigeria versus population in Indianapolis, in fact,
a very direct Nigerian descent and one can find in that sort of
comparison, a very significant increase in the proportion of
Alzheimer's disease in those individuals who now reside in the
United States.
Similarly, there have been comparisons of Japanese,
Japanese Americans in Hawaii, Asian Americans, which have
indicated the change and prevalence of Alzheimer's, it appears,
over a generation with a change of environment. These are
important because it is unlikely although not yet definitely
established that these changes result from selective genetic
differences but more likely, do reflect the impact of
environmental risk factors.
So we know that populations, when studied in some of these
discreet areas, do differ. We don't have a global national/
international comparison.
Senator Mikulski. You could also go to diet. Dr. von
Eschenbach, you seem eager to say something here.
Dr. von Eschenbach. Dr. Gerberding is right. I just wanted
to emphasize one other element of this equation. I think it has
been pointed out, we really do need to continue our investment
into the discovery end of the continuum, to learn more about
this disease so we're not just recognizing it when we're
looking at the end stages of the degenerative process and
people have already lost function. And at the same time, we
have to have attention to the deliver end of the continuum so
we get the kind of prevention and intervention that Senator
Mikulski was talking about.
But there's that middle piece between discovery and
delivery of development and I think we need a strategic
approach to that from the perspective that we are going to need
platforms, be they genetic or genomic platforms or whatever
that helps to find risk. Who is likely to succumb to this
disease? We need platforms for earlier diagnosis. They may be
imaging strategies. They may be nano-technology strategies. We
need development of interventions that are going to prevent the
disease at its very earliest stages before someone has
obviously lost the ability to remember where their keys are.
So that development piece has to be thought of
strategically, as where in this disease process, given what we
know about its molecular basis, can we target and define and
develop interventions that are going to help us predict,
detect, prevent and when necessary, intervene and hopefully
even reverse. I don't think we should lose sight of that in
this overall approach that you are fostering, to say we, as a
nation, have to do something about this disease from the very
beginning through its entire course.
Senator Mikulski. Thank you. I think that's an excellent
point. I just want to ask one other question and then maybe we
can go to wrap-up. I know Dr. Gerberding has got to leave and
we already delayed the hearing and I'm sure you all have, we
know you have ongoing responsibilities.
Dr. Zerhouni, you talked in your testimony about the
Alzheimer's disease cooperative study and in it, you talk about
something called the ADCS drugs. You say they are not typically
studied by the large pharmaceutical companies that are off
patent or were patented and are marketed for another use. Here
goes my question--is this an area when we look at our overall
framework for our legislation, we should be sure that we
specifically mention and also in Appropriations that this is an
area where you do things that the private sector--that's not
where the private sector is going to go. They might add value
to what you're doing but you're spending $52 million on this
over 6 years, which is what? Seven million dollars a year or
five, six and a half million?
Dr. Zerhouni. Eight, eight and a half.
Senator Mikulski. Yes. Is this an area that we should----
Dr. Zerhouni. Right. There is definitely a need for that
because obviously as you know, what we do at NIH--think of it
as a pyramid for our budget and our efforts. Sixty percent of
what we do is really the basic discovery, understanding the
disease. Twenty-five percent is what we call translational.
When we have an idea and we want to have a proof of concept at
a very early stage so that eventually, this will become an
incentive, if you will, for the private sector to take it and
develop it further and 15 percent, we spent on really doing,
for example, things in orphan diseases where at one point there
was no incentive, really, to develop these treatments for rare
conditions.
So in the ADCS, what the institutes--the National Institute
of Aging, National Institute of Neurological Diseases have come
together in a collaboration to say, when we have gaps like
this, how do you tackle them and it's not so easy. Because
you're talking about doing, for example, trials on things that
may be very useful but they are not patentable and therefore,
no one is going to do them. So you have cracks in the system
from either the need for us to do a trial on drugs that exist
that are not patented, that the FDA has already approved, but
that may be useful--in fact, one of the treatments for
Alzheimer's disease actually was out of patent and became quite
useful in the treatment of Alzheimer's disease early, and
delayed the onset of the disease.
So we do need to have a framework to understand the gaps in
the system. Like the Institute for example, will fund young
scientists with good ideas who have no access to what a drug
company would have access to. They can't figure out if the idea
they have is going to be positive and then be followed. So
that's something that NIH has to do but it's very, very
expensive and very difficult.
One of the things that we did through the Roadmap for
Molecular Research is we built what we call a molecular library
system for all academic sector investigators who can have
access to it for all diseases so that we can at least allow our
scientists to fill those gaps.
Senator Mikulski. Well, first of all, I find that very
instructive. I want to thank all of you for coming. I think
it's been a very enlightening and instructive conversation. I'm
going to reiterate what Senator Burr said, which is an
invitation now to take a look at our legislation. Our
legislation really has two parts. What we call the Alzheimer's
Breakthrough doubles the funding for NIH research and some of
the others and then there is a second component that will
really go to the Finance Committee on some tax breaks for
caregiving and we'll be looking at caregiving later on. But
we're not going to slow that down for what we want for our
Alzheimer's Breakthrough. So we ask you now to think about what
we could be emphasizing in the bill or authorize that would
really enhance prevention and be willing, as an approach, for
prevention of all chronic challenges that our population is
facing because there seems to be so many similarities that
there will be consensus within the public health community.
Second, how you think in our legislation, we can make sure
that we help with the Healthy Brain Initiative, which everyone
worked on and is so promising because I think the way we both
see it, is one, we don't want to be disease d'jour. This is a
very important issue. A national epidemic is on its way but we
want to do this in a way that's really a groundwork to help you
be you that would have a multiplier effect with so many other
things you're working on.
But to just conclude about Alzheimer's, I do see an analogy
with diabetes again and that's a situation where my own mother
died because of the consequences of it. She started on oral
insulin at age 40 and died at about 82. But look at where we
are now. When Mother was first diagnosed, it was diabetes, yes
or no. And you had either the injected insulin or this enormous
breakthrough called Diabinese, which was of great help. Then
she had to go for her test but then came something called Home
Testing, which looked like a 13-inch TV set. Now you can test
at home with reasonably 75 percent accuracy, Senator Burr, with
something that looks like a stopwatch. And when you look at the
array now, one would say this is a genetic propensity.
We start back here. You have to say goodbye to the baklava,
you have to say goodbye to the pirogue. You have to say hello
to broccoli and so what. It sure beats some of the other things
and then moving along to dealing with insulin resistance to all
these other kinds of tools. There are now 300 or more things
that her primary care physician or endocrinologist could have
had of avail. And this is, I think, the way we see here. Back
here, the prevention we're talking about would be for all
chronic illness and really get that going because we will do no
harm in helping diet and exercise, physically and mentally and
really getting this out in any way we can and particularly in
the centers where seniors gather and then to look at what are
the other continuum of things like we now see because it's no
longer diabetes, yes or no. It starts before you see it. It's
been insulin resistance and then it progresses.
But at the end of the day, you don't want to have that
disintegration in mitro-vascular disintegration of your
neurons, your kidneys and your eyes and with what we now know,
look what's already happening. So diabetes now, rather than a
cure, is viewed as a chronic illness and if controlled and
managed with so many tools, you're preventing the consequences
of it and so on.
So this is where we see heading to diet with Alzheimer's
and this is the continuum here. But we want to work with you to
get this going and I mention this because I think this is the
way you see it, too. From genetic propensity--not genetic
determinism--but genetic propensity, all the way through to
what we can do for prevention, intervention and in each passing
year, to get even more precise about it.
So Senator Burr, do you want to say something?
Senator Burr. I'd only end this way, Madam Chairman. I
think the big question is, what is our role? We need you to
share that with us, not just limited to Alzheimer's. What is
the role Congress can play today in the agencies that you head
that best helps you to do what we've asked you and your many
talented employees to do? Because at the end of the day, this
is about the impact that we can make on the quality of life of
individuals and what the cost of healthcare looks like in the
future.
I thought as the Chairman talked about the advances in
diabetes, a month ago, actually being at a Community Health
Center, seeing a remote monitor where an individual could take
it home or could run the software on their computer where it
could check their blood sugar multiple times a day, not just
for the purposes of them but for the purposes of their doctor
electronically receiving it and knowing exactly the tolerance
that they've been able to maintain on their blood sugar or for
the congestive heart patient who hooks up to five times a day,
remotely transmits that to a cardiologist.
The cardiologist can detect whether there is fluid that's
beginning to form, can verbally call and change that
individual's medication, which eliminates that emergency room
visit. The 3-day stay, as they begin to mobilize again and then
a routine back on medication.
We have the capabilities today to make sure that a
physician and a patient do exactly the right thing on disease
management and it's back to something you said, Dr. Zerhouni.
At some point, we have to figure out how to pay for it, if in
fact we want people to implement it and to use it. I go back
to, I think what we started on, this hearing, when the Chair
talked about HIV/AIDS and the reality is that when did people
get serious about a cure for HIV/AIDS? It was really when we
realized that it was cheaper to make sure that everybody with
HIV got drugs because we knew exactly how many hospital visits
they were going to have that year. We knew the cost of those
hospital visits at the time, the original time, was about
$25,000 a year. A case of pneumonia. A case of retinal eye
infection. They'd visit twice but for $14,000, we could give
them the medication and save ourselves a $25,000 inpatient
experience twice a year.
That's a budgetary answer to something that also has a
quality of life component and that's that we stop disease in
its tracks, but the reality is that sometimes it takes
understanding what we're saving to understand what we're
willing to invest. Unfortunately, we don't have a scoring
mechanism within the Congress that we can dynamically score
things to show us what we save. It will only show us what we
spend. That's where we're going to have work in partnership
together to make sure that we implement the right types of
policies that not only address the quality of life but address
the budget savings that is absolutely vital for us to be able
to pay for it. I thank the Chairman. I thank our witnesses.
Senator Mikulski. Well said and yes, this committee stands
in adjournment, subject to the call of the Chair and at that
time, we will begin to proceed to mark up our bill. We want to
thank all of our witnesses for their outstanding contribution.
[Additional material follows.]
ADDITIONAL MATERIAL
Prepared Statement of Senator Clinton
I would like to thank Chairman Mikulski and Ranking Member
Burr for convening today's hearing on what we are presently
doing at the Federal level to combat the growing threat that
Alzheimer's poses to the health of our citizens, our healthcare
system, and our Nation's financial resources.
I applaud Senator Mikulski for her tireless work on issues
related to Alzheimer's disease, and I'm proud to work with her
and Senator Bond on the Alzheimer's Breakthrough Act. This
important legislation is critical in our fight against the
disease, and I look forward to its markup in the HELP Committee
next week.
Last week I joined Senators Mikulski and Burr, as well as
my fellow co-chair of the Senate Alzheimer's Task Force,
Senator Collins, in welcoming the creation of a new Alzheimer's
Disease Study Group. As envisioned by the Alzheimer's
Association, this Study Group would be an independent, non-
partisan collection of health policy experts who will assess
America's current approach to Alzheimer's and will develop new
strategies for how the private and public sectors can better
meet the challenges posed by this devastating disease.
Former Speaker Newt Gingrich and former Senator Bob Kerrey
have agreed to take the lead as co-chairs of the Alzheimer's
Disease Study Group. The combination of balanced, independent
viewpoints and expert opinion should make a strong contribution
to America's current efforts to combat Alzheimer's disease, and
I look forward to the release of the Alzheimer's Disease Study
Group's findings and recommendations.
While outside advice is important in the fight against this
terrible disease, it is our responsibility as elected officials
to do all we can to advance the cause of prevention, diagnosis,
and treatment of Alzheimer's, including rigorous examination of
whether we are doing all we should at the Federal level.
Are we setting aside enough resources so that current
researchers have the tools they need to investigate the
etiology of this disease? Are we prioritizing the recruitment
and training of the next generation of scientists and
physicians who will make finding a cure for this disease their
life's work? Are we doing all we can to support the millions of
caregivers who make tremendous personal sacrifices--and suffer
emotionally, mentally, physically and financially--in order to
take care of and advocate for someone who is suffering from
Alzheimer's? Are we making every effort to safeguard the mental
health and physical well-being of adults with Alzheimer's and
other dementias--who constitute one of our most vulnerable
populations?
Even as we pause to take assessment of our actions and ask
ourselves these questions--the toll of the disease continues to
grow. An estimated 5.1 million Americans now have Alzheimer's--
and their loved ones and caretakers wake up every day and not
only provide support and comfort for a loved one, but confront
the difficult toll of the disease. We are approaching a crisis
as the Baby Boom generation grows older. By the year 2050, up
to 16 million older Americans are expected to be living with
Alzheimer's.
This stark increase is more than a statistic. It represents
millions of families facing an emotional struggle and
tremendous financial pressure; a new strain on our healthcare
system; new costs for Medicaid and Medicare.
For the past 3 years, Senator Collins and I have co-chaired
the Senate Task Force on Alzheimer's Disease. We have
highlighted the importance of early detection of Alzheimer's;
helping people with Alzheimer's and providing support services
for their families and caregivers; highlighting promising
research findings that suggest that healthy diet, regular
exercise, as well as social and mental activity may help to
decrease the risk of Alzheimer's; and the latest innovations
for facilitating early detection and intervention.
Senator Collins and I are also working to improve older
Americans' access to mental health services. Diseases such as
Alzheimer's can contribute to depression and anxiety for both
those who suffer from the disease as well as their caretakers.
In last year's reauthorization of the Older Americans Act, we
successfully enacted Title I of the Positive Aging Act of 2005
which authorized grants for the delivery of mental health
screening and treatment services for older adults and grants to
promote awareness and reduce stigma regarding mental disorders
in later life.
While this took an important step toward improving mental
health services for older adults, significant efforts are
necessary to ensure comprehensive geriatric mental health care.
That is why Senator Collins and I introduced the Positive Aging
Act of 2007, which will integrate mental health services into
primary care and community settings.
But improving access to mental health services is just one
element of responsibly providing the care that Alzheimer's
patients require. The majority of caregivers have outside
employment in addition to their caregiving responsibilities at
home. Research tells us that, because of the lack of support
services, most caregivers either miss work or quit their jobs
in order to meet the health needs of their family members.
Respite care services provide temporary relief for
caregivers and decrease the likelihood of formal long-term
care, thereby resulting in significant savings for the
healthcare system and taxpayers. Further, respite care also
provides family caregivers with the relief necessary to
maintain their physical and mental health, as well as bolster
family relationships.
Last December, my Lifespan Respite Care Act was enacted
after 4 years of bipartisan effort. The law will help millions
of Americans who struggle to provide care for a family member
with a chronic illness or disability so they may remain at home
and out of more expensive institutional care. Now we are
working to fund the bill with $300 million over 5 years.
Compare that to nearly $300 billion--the cost of the services
family members provide as caretakers of a sick or disabled
loved one.
A great deal has been achieved in the last 15 years in the
awareness, diagnosis, and treatment of Alzheimer's disease. But
much more still needs to be done. We must continue to make
Alzheimer's a national priority. The more we learn, the further
we travel on the path toward a world without Alzheimer's--and
we know that we cannot travel on that road quickly enough.
[Whereupon, at 5:04 p.m., the hearing was adjourned.]