[Senate Hearing 108-770]
[From the U.S. Government Publishing Office]



                                                        S. Hrg. 108-770

        BREAKTHROUGHS IN ALZHEIMER'S RESEARCH: NEWS YOU CAN USE

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

                                HEARING

                               BEFORE THE

                         SUBCOMMITTEE ON AGING

                                 OF THE

                    COMMITTEE ON HEALTH, EDUCATION,
                          LABOR, AND PENSIONS
                          UNITED STATES SENATE

                      ONE HUNDRED EIGHTH CONGRESS

                             SECOND SESSION

                                   ON



EXAMINING BREAKTHROUGHS IN ALZHEIMER'S DISEASE (AD) RESEARCH, FOCUSING 
     ON RISK FACTORS FOR DEVELOPING AD, DEVELOPING SAFE, EFFECTIVE 
  PREVENTIONS AND TREATMENTS FOR AD, AND ``THE MAINTAIN YOUR BRAIN'' 
                                CAMPAIGN

                               __________

                              MAY 11, 2004

                               __________

 Printed for the use of the Committee on Health, Education, Labor, and 
                                Pensions



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          COMMITTEE ON HEALTH, EDUCATION, LABOR, AND PENSIONS

                  JUDD GREGG, New Hampshire, Chairman

BILL FRIST, Tennessee                EDWARD M. KENNEDY, Massachusetts
MICHAEL B. ENZI, Wyoming             CHRISTOPHER J. DODD, Connecticut
LAMAR ALEXANDER, Tennessee           TOM HARKIN, Iowa
CHRISTOPHER S. BOND, Missouri        BARBARA A. MIKULSKI, Maryland
MIKE DeWINE, Ohio                    JAMES M. JEFFORDS (I), Vermont
PAT ROBERTS, Kansas                  JEFF BINGAMAN, New Mexico
JEFF SESSIONS, Alabama               PATTY MURRAY, Washington
JOHN ENSIGN, Nevada                  JACK REED, Rhode Island
LINDSEY O. GRAHAM, South Carolina    JOHN EDWARDS, North Carolina
JOHN W. WARNER, Virginia             HILLARY RODHAM CLINTON, New York

                  Sharon R. Soderstrom, Staff Director

      J. Michael Myers, Minority Staff Director and Chief Counsel

                                 ______

                         Subcommittee on Aging

                CHRISTOPHER S. BOND, Missouri, Chairman

LAMAR ALEXANDER, Tennessee           BARBARA A. MIKULSKI, Maryland
MIKE DeWINE, Ohio                    EDWARD M. KENNEDY, Massachusetts
PAT ROBERTS, Kansas                  PATTY MURRAY, Washington
JOHN ENSIGN, Nevada                  JOHN EDWARDS, North Carolina
JOHN W. WARNER, Virginia             HILLARY RODHAM CLINTON, New York

                    Kara R. Vlasaty, Staff Director

                Rhonda Richards, Minority Staff Director

                                  (ii)






                            C O N T E N T S

                               __________

                               STATEMENTS

                         Tuesday, May 11, 2004

                                                                   Page
Bond, Hon. Christopher, a U.S. Senator from the State of 
  Missouri, opening statement....................................     1
Mikulski, Hon. Barbara A., a U.S. Senator from the State of 
  Maryland, opening statement....................................     2
Dodd, Hon. Christopher J., a U.S. Senator from the State of 
  Connecticut, opening statement.................................    35
Hodes, Richard J., M.D., Director, National Institute of Aging, 
  National Institutes of Health, Bethesda, MD; John C. Morris, 
  M.D., Friedman Distinguished Professor of Neurology, Washington 
  University School of Medicine St. Louis, MO; Peter V. Rabins, 
  M.D., Professor, Department of Psychiatry, Johns Hopkins 
  University School of Medicine, Baltimore, MD; and Stephen 
  McConnell, Senior Vice President for Advocacy and Public 
  Policy, Alzheimer's Association, Washington, DC................     5
    Prepared statements of:
        Dr. Hodes................................................     8
        Dr. Morris...............................................    17
        Dr. Rabins...............................................    19
        Mr. McConnell............................................    23
Hall, Eric, CEO, Alzheimer's Foundation of America, prepared 
  statement......................................................    31

                          ADDITIONAL MATERIAL

Statements, articles, publications, letters, etc.:
    Academy of Molecular Imaging (AMI)...........................    47

                                 (iii)

  

 
        BREAKTHROUGHS IN ALZHEIMER'S RESEARCH: NEWS YOU CAN USE

                              ----------                              


                         TUESDAY, MAY 11, 2004

                                       U.S. Senate,
        Subcommittee on Aging, of the Committee on Health, 
                            Education, Labor, and Pensions,
                                                    Washington, DC.
    The subcommittee met, pursuant to notice, at 10:02 a.m., in 
room SD-430, Dirksen Senate Office Building, Hon. Kit Bond 
(chairman of the subcommittee) presiding.
    Present: Senators Bond, Mikulski, and Dodd.

                   Opening Statement of Senator Bond

    Senator Bond. Good morning. The hearing of the Subcommittee 
on Aging of the Senate Committee on Health, Education, Labor, 
and Pensions will come to order.
    Today we are here to discuss a very important and very 
difficult problem, that of Alzheimer's disease.
    We welcome the distinguished panel and look forward to 
their sharing with us their views and possible rays of hope 
that they have for making progress on this very troubling 
disease.
    It is a devastating disease with a deep impact on 
individuals, families, and our health care system, making this 
disease one of our country's greatest medical, social, and 
fiscal challenges.
    Being parochial, I look at how it affects my State of 
Missouri, Senator Mikulski. In Missouri alone, there are over 
108,000 people with Alzheimer's disease. Based on population 
growth, unless science finds a way to prevent or delay the 
onset of this disease, that number will increase to over 
159,000 by 2025.
    Today throughout the United States, approximately 4.5 
million Americans have Alzheimer's, with annual costs in 
economic terms for this disease estimated to exceed $100 
million. Based on current trends, by 2050, 11 to 16 million 
individuals could have this disease.
    If these predictions become a reality, it could overwhelm 
our health care system and bankrupt Medicare and Medicaid. The 
numbers speak for themselves: Medicare costs for a person with 
Alzheimer's are almost three times greater than the average for 
all beneficiaries. And as the baby boomers age, the costs to 
the Medicare program will grow as well. The costs to Medicare 
will reach $50 billion in less than 10 years. The costs to 
Medicaid will increase 80 percent to $33 billion annually in 
less than 10 years.
    And those are just the economic costs. The family costs and 
the human costs--those are the real tragedies. We have had the 
example of a former President who announced that he had 
Alzheimer's, and his wife has been a true champion in 
discussing very frankly the very tragic and difficult 
circumstances through which families go as a loved family 
member suffers and declines with Alzheimer's.
    I know too many of them myself, whose wife or father or 
mother has suffered from Alzheimer's. I know my distinguished 
colleague has had great experience. And forget about the 
economic costs; the human costs, the lost touch with a loved 
one--I think Mrs. Reagan said that ``He has gone to a place 
where he cannot be reached.'' That is the tragedy--that is the 
tragedy--that so many families confront today.
    But over the past 20 years progress has been made in 
prevention, diagnosis and treatment of Alzheimer's. I 
understand that it is now possible to diagnose Alzheimer's with 
more than 90 percent accuracy. New drugs and new treatments are 
being introduced each year, and investments in research have 
set the stage for scientific and medical advances to prevent or 
slow the progression of this dreaded disease.
    Alzheimer's research is producing some groundbreaking 
discoveries that offer hope for the 4.5 million people 
suffering from the disease today.
    Today we are honored to have before the subcommittee a 
distinguished panel of doctors, researchers, and advocates to 
discuss Alzheimer's disease and the progress being made toward 
the understanding, diagnosis, treatment, and prevention of 
Alzheimer's disease.
    I now turn to my distinguished colleague, the Senator from 
Maryland, Senator Mikulski, who has a deep and abiding interest 
as well as experience with Alzheimer's.
    Senator Mikulski?

                 Opening Statement of Senator Mikulski

    Senator Mikulski. Thank you very much, Chairman Bond, for 
holding this hearing on breakthroughs in Alzheimer's research 
and also, for families dealing with this, essentially ``news 
that they can use''--either things they can do to help their 
families, also to be able to give them hope, and also to 
explore ways where they are not going down efforts that will 
only lead to disappointment.
    We are very pleased to have such a distinguished panel here 
of, as you said, leading research people, both research and 
clinicians, as well as the leading advocate organization, the 
American Alzheimer's organization, which has pursued both 
research and then ways for caregiving.
    Today's hearing is going to focus on breakthroughs, 
providing information that will really tell us new facts and 
new ideas about breakthroughs in diagnosis, promising research 
pertaining to drugs and treatment, ideas on prevention 
techniques, and even research that might be going on 
internationally.
    This topic is very near and dear to me for several reasons. 
My own father, a wonderful man, endured this himself, and Dr. 
Rabins' famous book, ``The 36-Hour Day,'' was of such a big 
help to my family and myself in really understanding what our 
father was dealing with and what we would have to deal with.
    I am very pleased that the National Institute of Aging at 
NIH also has its primary site in Baltimore, at the Bayview 
Campus of Johns Hopkins, where leading geriatric research is 
going on. And, Senator Bond, when election years are not upon 
us and so on, you need to know that it is over there right 
nextdoor to a neighborhood that we call ``Greek Town,'' so if 
you want to come and see leading-edge research and have a 
little heart-smart calamari, we will be happy to have you.
    Senator Bond. That sounds like a deal. Is that before or 
after we have the crabs?
    Senator Mikulski. We can just do it all day--but one of the 
things they are going to tell us is that the less you weigh at 
70, the better your chances of not getting Alzheimer's.
    We have made tremendous strides in improved diagnostic 
tools, helping providers to diagnose with 90 percent accuracy. 
This is really important, because when my Dad faced this in the 
mid-eighties, Alzheimer's was even becoming a catch-all for any 
form of memory loss, which was not good for the patient and not 
good for the family and, quite frankly, not good for the 
Medicaid system. So we are looking forward to hearing about 
those issues and the other issues related to medications that 
can alleviate the symptoms of Alzheimer's and also the 
increased knowledge of prevention.
    This is why we are holding this hearing today, to hear from 
researchers and advocates as well as those involved in actual 
clinical work about these breakthroughs. Family caregiving for 
a family member with Alzheimer's faces these financial, 
physical, and emotional 36-hours days. I am fighting to make 
sure we help those families out, and in fact have introduced a 
$5,000 tax credit that if you have a family member with a 
chronic disease that requires medical management or 
supervision, you can get a $5,000 tax break for prescription 
drugs, specialized day care and specialized home care. I know 
it is another committee, but it is something to put out.
    In terms of research, Senator Bond has talked about what it 
means in both Missouri and nationwide. We know that right now, 
1.6 million Medicaid recipients are in nursing homes. About 
half of them, 800 million people, suffer from Alzheimer's. The 
impact on the families and the impact on the Medicaid budget is 
really severe. If we could have any type of breakthrough, for a 
cure or for prevention or even for cognitive stretch-out, every 
month that we can delay admission to a long-term care facility 
is important to the family and important to the taxpayer. Any 
month that we can delay would have those consequences.
    If we can delay the onset or have cognitive stretch-out 
approaches and methodologies, I think it would be stunning. 
Everybody needs a cure, but even if we were able to keep people 
at home and keep memory and other functioning, it would be a 
great breakthrough.
    So we are looking forward to hearing the testimony. We are 
very proud of the fact that our leadership worked from 1998, 
Senator Bond, when the National Institute of Aging budget was 
about $500 million, and working together with our 
appropriations--and we are the appropriators as well on another 
committee--we increased it to $1 billion. This is very good--
and it is not only Alzheimer's, and we want to hear from you, 
Dr. Hodes--we also have other legislation pending--the 
Alzheimer's Disease Research and Care Act of 2003, as well as 
looking at where we are going.
    I will talk about where we are going after we have heard 
from our panel. But we are looking for promising research, and 
we are also looking for new approaches, like the chelation 
approach you talked about. And then also, we do know that there 
are other activities going on at NIH in the field of 
complementary medicine, and we look forward to getting some 
input from Dr. Straus.
    But rather than me talking, we really want to hear from 
you. And I cannot thank you enough for what you are doing every 
day in your day-to-day work, whether it is heading up the NIH 
on research, whether it is heading up the advocacy 
organization, where they are being both clinicians and 
researchers, because you are truly making a difference. We 
welcome your enthusiasm and want to know how we can be on your 
side.
    Thank you, Mr. Chairman.
    Senator Bond. Senator, speaking about getting to the 
witnesses, we have the distinguished CVs of these four 
outstanding leaders, and we can either spend the day reading 
them or hear their testimony. And if you have no objection, I 
am going to introduce the full resumes of all of our speakers 
and just tell you very briefly about them.
    The first witness will be Dr. Richard Hodes, Director of 
the National Institute of Aging, NIA, at NIH. NIA is the 
principal Federal funding agency for studies of the basic, 
clinical, epidemiological, and social aspects of aging. Dr. 
Hodes was named Director of NIA in 1993 but has enjoyed a long 
career in science at NIH as an investigator in the National 
Cancer Institute.
    From the State of Missouri, we have Dr. John Morris, the 
Harvey A. and Dorismae Hacker Friedman Distinguished Professor 
of Neurology at the Washington University School of Medicine, 
as well as professor of pathology and immunology and of 
physical therapy. He is director of the Alzheimer's Disease 
Research Center, Memory and Aging Project, and Memory 
Diagnostic Center at the School of Medicine and Barnes-Jewish 
Hospital, and also is director of the Center for Aging at 
Washington University.
    Dr. Morris is the principal investigator for the program 
project, ``Healthy Aging and Senile Dementia,'' and for the 
Alzheimer's Disease Research Center at Washington University, 
both funded by the NIA. He obtained a Leadership Award from the 
NIA for the Center on Aging.
    I would like to turn over the next introduction to Senator 
Mikulski before introducing the final panelist.
    Senator Mikulski. We also welcome Dr. Peter Rabins. He has 
been a member of the faculty of Hopkins since 1978. He is 
director of the Geriatric Psychiatric Program, and he has 
focused his career on psychiatric disorders of older persons.
    In addition to this hands-on care as well as his research, 
he is the author of 180 articles, and his famous ``The 36-Hour 
Day'' book about what families and patients endure was first 
published in 1981 and is as current today as it was then in 
terms of the insights. Also, in 1999, he published a book 
titled, ``Practical Dementia.''
    But the committee should be aware that there is a 
newsletter that Hopkins puts out called ``Health After 50.'' 
This is a newsletter for consumers to get the latest thinking 
on prevention, treatment, and so on, and his article, ``Help 
for Early Alzheimer's'' gave us a very good thumbnail sketch of 
some of the breakthroughs. So in addition to being members of 
the ``genius club'' at Hopkins, they actually can talk like 
regular people so we will know what they are saying.
    Senator Bond. That will be very helpful.
    Senator Mikulski. And we welcome him with enthusiasm.
    Senator Bond. Our final witness that we are delighted to 
welcome today is Mr. Stephen McConnell, senior vice president 
for advocacy and public policy at the Alzheimer's Association.
    Before joining the Association, he spent 7 years on the 
Hill as staff director of the Senate Special Committee on Aging 
under Chairman John Heinz and as a professional staff member 
for the U.S. House of Representatives Select Committee on Aging 
under the chairmanship of Representative Claude Pepper.
    Mr. McConnell has been a teacher and has published in the 
fields of gerontology and social policy, and he holds a Ph.D. 
in sociology from the University of Southern California.
    Gentlemen, we are delighted to welcome all of you, and with 
that, we will hear your statements. We have a timer up here set 
for 5 minutes, and we will take your full statements for the 
record, and we would like to go several rounds of questions.
    So if you would please begin, Dr. Hodes, and we will take 
your full statement for the record.

   STATEMENTS OF RICHARD J. HODES, M.D., DIRECTOR, NATIONAL 
 INSTITUTE ON AGING, NATIONAL INSTITUTES OF HEALTH, BETHESDA, 
 MD; JOHN C. MORRIS, M.D., FRIEDMAN DISTINGUISHED PROFESSOR OF 
NEUROLOGY, WASHINGTON UNIVERSITY SCHOOL OF MEDICINE, ST. LOUIS, 
MO; PETER V. RABINS, M.D., PROFESSOR, DEPARTMENT OF PSYCHIATRY, 
JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE, BALTIMORE, MD; AND 
   STEPHEN McCONNELL, SENIOR VICE PRESIDENT FOR ADVOCACY AND 
     PUBLIC POLICY, ALZHEIMER'S ASSOCIATION, WASHINGTON, DC

    Dr. Hodes. Thank you, Senator Bond and Senator Mikulski, 
for the opportunity to appear before you.
    You have both very eloquently introduced the scope of the 
human and societal challenges posed by Alzheimer's disease, a 
topic of great interest and concern to us all.
    In our quest to better understand the disease's starting 
point for learning how to deal with it, we search commonly for 
risk factors. The most telling risk factor for Alzheimer's 
disease currently understood is of course age, dramatically 
illustrated by the fact that nearly one-half of individuals age 
85 and older are afflicted with the disease, and this, plus the 
projected increase in the number of older individuals in 
America, comprises the real urgency that you have introduced in 
your own comments.
    Among the risk factors that have been identified are both 
genetic and environmental ones. We have identified three genes 
which are responsible for early onset Alzheimer's disease, and 
these have been invaluable in pointing to mechanisms, molecular 
and cellular, that provide new targets for interventions to 
come, in addition to identifying one major risk factor for late 
onset disease, the APOE gene.
    We recently announced and I am happy to say have now 
implemented a new Genetics Initiative that is a collaboration 
among many of the Alzheimer's centers and investigators with 
the goal of identifying yet more genes involved as risk 
factors, again to the end of identifying new targets of 
intervention.
    We are also greatly concerned with identifying modifiable 
risk factors. Among them are those that are cardiovascular risk 
factors as well. And one, to note a recent report, is diabetes. 
Diabetes, a disease which afflicts some 17 million Americans, 
has been shown to be associated with increased risk of loss of 
cognitive function and of Alzheimer's disease.
    One recent study identified that in older women with Type 2 
diabetes, the risk of Alzheimer's disease was increased, but 
that in women who were successful in controlling their blood 
sugar levels, in fact risk was reduced to the level of 
nondiabetics. In pursuit of this as a potential intervention, 
NIH is currently supporting a study, ACCORD, in which we will 
determine in a controlled clinical trial whether vigorous 
control of blood sugar will in fact be effective in preventing 
loss of cognitive function and the rate of development of 
Alzheimer's disease.
    In addition to this search for risk factors, one of the 
modalities that has been particularly promising of late has 
been that of imaging. As was noted, we are now looking very 
seriously at ways in which we can move beyond the studies--this 
is illustrated on one of the slides presented to you--from a 
time when we were focused largely on Alzheimer's disease and 
its treatment, to the right of the slide, that is, in patients 
who already had the disease. Much of the goals of our research 
are now focused on looking at mild cognitive impairment, an 
earlier stage, and even at the stages before any symptoms have 
been developed, stages that could be identified by imaging and 
psychological testing, points at which intervention may be more 
effective than at later stages of the disease.
    Among the imaging techniques which have most recently 
provided advances in the field is one illustrated here--for the 
first time, development of a series of dyes or tracers which 
can actually stain amyloid, one of the components of lesions 
commonly seen in Alzheimer's disease. So you can see in the 
panel on your left marked ``Control,'' this is the PET scan or 
the brain image of an individual who is a control without 
disease, and there is very little staining--that is what the 
blues and greens indicate--for amyloid. In contrast, the 
Alzheimer's patient on the right, with red as the most intense 
area, shows that in a living patient, it is now possible to 
identify the lesions which mark the disease. The greatest 
utility of this potentially is to provide an opportunity for us 
to identify individuals with disease and to trace the process 
of treatment by looking at alterations in brain rather than 
having to wait until they are manifest in symptoms. That is 
potentially accelerating the pace of developing new and 
effective interventions.
    A year ago, we announced to the appropriations subcommittee 
plans for a Neuroimaging Initiative, and I am pleased to say 
that those plans have now been translated into reality with an 
initiative about to be funded in August with patients to be 
accrued later this year. This is an initiative that is intended 
to look at modalities such as PET and MRI in individuals with 
Alzheimer's, in those with mild cognitive impairment, and in 
normal individuals, to find the most precise ways by imaging 
all other biological markers to mark disease and disease 
progress.
    The goal here is important. It is to find ways to identify 
disease early and then to most effectively identify which 
treatments are having an impact on the basic underlying brain 
changes of Alzheimer's disease. This initiative is really a 
remarkable collaboration of several components of NIH, together 
with the Food and Drug Administration who will ultimately be 
responsible for approving drugs that may be based on 
interventions using imaging such as this, the Centers for 
Medicare and Medicaid Services, who will be critically involved 
in approving the use of such agents, as well as the private 
sector pharmaceutical industry, who are contributing 
significant amounts of funding to this, and the neuroimaging 
industry itself.
    Through all of these approaches and what has been learned 
about basic science, we have now developed for the first time a 
large number of interventions under study, illustrated here in 
summary, that are using agents such as anti-inflammatories, 
interventions designed to attack cardiovascular risk factors, 
and notably, ginkgo biloba, as an example of approaches to 
complementary and alternative medicine. We should note that 
this study, involving some 3,000 individuals, in collaboration 
with the National Center for Complementary and Alternative 
Medicine, is in fact the largest current clinical study of 
plant drugs currently under study.
    This is only the beginning, and we look forward to 
translating the current generation of basic science into yet 
another iteration of effective clinical trials.
    And finally, to comment on the burden that has been 
referred to, the important burden of caregivers. Until we have 
been successful in eradicating Alzheimer's disease, we also 
take seriously the commitment to direct research at the issue 
of caregiving. Most of the four million-plus Americans 
currently affected with Alzheimer's disease are cared for not 
in institutions but by family, by loved ones, individuals who 
themselves are subject to great stress manifest in physical as 
well as emotional toll. And studies such as a clinical trial 
called REACH, Research to Enhance Alzheimer's Caregiver Health, 
are currently underway in parallel with studies to approach the 
disease itself or those studies which tell us how to best deal 
with the caregiver burden that is a part of the current 
disease.
    Again, Senator Bond, Senator Mikulski, I appreciate the 
opportunity to appear before you and look forward to answering 
any questions that you might have.
    Senator Bond. Thank you very much, Dr. Hodes.
    [The prepared statement of Dr. Hodes follows:]
              Prepared Statement of Richard J. Hodes, M.D.
    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. I am 
delighted to be here today to tell you about the progress we are making 
toward understanding, treating, and preventing AD.
    As you know, AD is a devastating condition with a profound impact 
on individuals, families, the health care system, and society as a 
whole. Approximately 4.5 million Americans are currently battling AD, 
with annual costs for the disease estimated to exceed $100 billion.\1\ 
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 annual number of 
incident cases 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 some 13.2 million, an almost three-fold increase.\2\
---------------------------------------------------------------------------
    \1\ Data from the Alzheimer's Association. See also Ernst, RL; Hay, 
JW. ``The U.S. Economic and Social Costs of Alzheimer's Disease 
Revisited.'' American Journal of Public Health 1994; 84(8): 1261-1264. 
This study cites figures based on 1991 data, which were updated in the 
journal's press release to 1994 figures.
    \2\ Hebert, LE; Scherr, PA; Bienias, JL; Bennett, DA; Evans, DA. 
``Alzheimer Disease in the U.S. Population: Prevalence Estimates Using 
the 2000 Census.'' Archives of Neurology August 2003; 60 (8): 1119--
1122.
---------------------------------------------------------------------------
    But these numbers, however stark, do not tell the whole story. 
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 and diagnose AD that offer us the hope of preventing and 
treating the disease, to reverse the current trends.

Risk Factors

    Many Americans wonder whether they or their loved ones are at risk 
of developing AD. Sadly, as they age, many of them will be. The risk of 
AD increases dramatically with age, with nearly half of all individuals 
over age 85 being diagnosed.\3\ In addition, many older Americans 
struggle with mild cognitive impairment (MCI), a condition that is 
frequently a precursor to AD; in one recent population-based study of 
cognition in the elderly, 22 percent of participants over 75, and 29 
percent of those over 85, were diagnosed with MCI.\4\ In a recent 
review of studies of MCI and AD, investigators noted that the rate of 
conversion from MCI to full-blown AD ranged from 6 to 25 percent per 
year; in one study cited by the authors, 80 percent of MCI patients had 
developed AD within 6 years of their initial diagnosis.\5\ Determining 
who is at high risk of developing AD and who is not--and why--will 
enable us to identify potential targets for preventive intervention, as 
well as those individuals who might benefit most from such 
interventions.
---------------------------------------------------------------------------
    \3\ Data from the Alzheimer's Association. See also Evans, DA; 
Funkenstein, HH; Albert, MS; et al. ``Prevalence of Alzheimer's Disease 
in a Community Population of Older Persons: Higher than Previously 
Reported.'' JAMA 1989; 262(18): 2552--2556.
    \4\ Lopez O, Jagust WJ, DeKosky ST, Becker JT, et al. ``Prevalence 
and Classification of Mild Cognitive Impairment in the Cardiovascular 
Health Study Cognition Study.'' Arch Neuro 60: 1385-1389, 2003.
    \5\ Petersen RC, Stevens JC, Ganguli M, et al. ``Practice 
parameter: Early detection of dementia: Mild cognitive impairment (an 
evidence-based review).'' Neurology 56: 1133-1142, 2001.
---------------------------------------------------------------------------
    Through laboratory, clinical, and population-based research, we 
have identified a number of risk factors for AD, including both genetic 
and lifestyle factors. We already know of three major genes for early-
onset disease and have identified a major risk factor gene, ApoE4, for 
the more common late-onset disease. Recent findings are enabling us to 
close in on several others, thought to be on chromosomes 9, 10, and 12.
    In addition, neuroscientists have become increasingly interested in 
a specific set of genes that may influence not whether, but when, a 
person might develop symptoms of neurodegenerative disease. Delaying 
the onset of AD symptoms by even 5 years could greatly reduce the 
numbers of people who will have the disease, as well as providing 
additional cognitively-healthy time to those who will eventually be 
diagnosed. Recently, NIH-supported investigators found a gene on 
chromosome 10 that they believe influences the age of onset of both 
Alzheimer's disease and Parkinson's disease. Using a novel method to 
match the genes of people affected with these diseases with the age at 
which study participants started developing symptoms, the scientists 
found that one gene, GSTO1, was significantly associated with late 
onset of both Alzheimer's and Parkinson's. This important work gives us 
new clues to the role of genetics in the timing of late-life forms of 
these devastating neurodegenerative diseases.
    NIA's AD Genetics Initiative is a program to accelerate the pace of 
AD genetics research by creating a large repository of DNA and cell 
lines from families with multiple AD cases. The goal of this initiative 
is to develop strategies for identifying the additional late-onset AD 
(LOAD) risk factor genes, associated environmental factors, and the 
interactions of genes and the environment. The NIA's AD Genetics 
Initiative will intensify sample collection and encourage data sharing 
by providing access to a national repository to qualified 
investigators.
    This year, we have launched several well-integrated components of 
the Genetics Initiative. Mechanisms to efficiently identify and share 
large numbers of samples for AD genetic analysis have been developed, 
and 18 of the NIA's Alzheimer's Disease Centers (ADCs) have received 
supplemental funding to recruit new family members for participation. 
Uniform standards for sample collection have also been developed. 
Recruitment is well underway; as of April, nearly 400 families, of the 
approximately 1,000 needed, have been evaluated and are now enrolled in 
the study, and over 1,000 blood samples have been collected. A major 
goal is the long-term follow-up of individuals participating in the 
study.
    Investigators have also identified a number of potential lifestyle 
factors that may increase risk of AD, a number of which can be modified 
through diet or lifestyle changes. These include cardiovascular 
disease, high blood pressure, stroke, and history of traumatic head 
injury. Just over 2 years ago, researchers found that individuals with 
high blood levels of the amino acid homocysteine had nearly double the 
risk of developing AD; a trial of homocysteine-lowering agents, 
including vitamins B6 and B12 and folate, to slow progression of AD is 
currently underway. Another clinical trial is ongoing to determine 
whether common cholesterol-lowering drugs known as statins can slow 
disease progression in patients with mild to moderate AD.
    Type 2 diabetes, which, according to the American Diabetes 
Association, affects approximately 17 million Americans, is another 
potential risk factor for cognitive decline and AD. In a recent study, 
researchers found that compared to older nondiabetic women, older women 
with type 2 diabetes were about 30 percent more likely to score poorly 
on tests of cognitive function, and that the risk increased with the 
duration of their condition. However, the diabetic women in the study 
who took glucose-lowering pills had a risk similar to nondiabetic 
women. Recognizing the potential link between type 2 diabetes and 
cognitive decline, NIA researchers are currently participating in an 
offshoot of the National Heart, Lung, and Blood Institute's Action to 
Control Cardiovascular Risk in Diabetics (ACCORD) study. ACCORD 
evaluates whether more intensive glucose, blood pressure and lipid 
management can reduce cardiovascular disease in people with diabetes; 
the aim of this sub-study, ACCORD-MIND, is to test 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 treated with intensive care guidelines. Recruitment for the 
ACCORD study began in January 2003, and we anticipate that 2,800 people 
will participate in ACCORD-MIND.

Diagnosis

    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; in fact, 
using the tools currently available, it may be possible to accurately 
diagnose AD more than 90 percent of the time.\6\ Furthermore, the 
development of new potential methods holds tremendous promise for 
improved diagnosis of AD. For example, there is at present no 
scientifically validated method to visualize AD's characteristic 
amyloid plaques and neurofibrillary tangles in a living human. However, 
researchers have recently developed a radiotracer called Pittsburgh 
Compound-B that facilitates visualization of amyloid deposition in 
living AD patients using PET scans. Although further research is 
needed, such molecules may eventually offer us a powerful and accurate 
diagnostic tool for the disease.
---------------------------------------------------------------------------
    \6\ Larson EB, Edwards JK, O'Meara E, Nochlin D, Sumi SM. 
Neuropathologic diagnostic outcomes from a cohort of outpatients with 
suspected dementia. J Gerontol A Biol Sci Med Sci 1996; 51(suppl 
6):M313-M318.
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    Powerful imaging techniques, including positron emission tomography 
(PET) and magnetic resonance imaging (MRI), are opening a window into 
the brain, allowing us to visualize not only anatomical structures but 
also functional processes and activities at the molecular level. The 
refinement of these techniques continues to have a profound effect on 
all areas of AD research.
    Visualization of brain structures and activities may also enable us 
to identify people at risk of developing the disease even decades 
before the onset of symptoms. In a recent study, investigators used PET 
to examine the brains of asymptomatic young adults (ages 20-39) who 
were carriers of the APOE-e4 gene, a common susceptibility gene for 
late-onset AD. Middle-aged carriers of this gene are known to have 
abnormally low rates of metabolism in the same brain regions as 
patients with AD; in this study, the investigators found the same brain 
abnormalities in the younger carriers of the gene. The precise link 
between the APOE-e4 gene, the altered metabolism, and AD remains 
unknown, and more research is needed on this provocative finding, but 
it may offer important clues to AD's etiology and perhaps even a target 
for future prevention efforts.
    Advances in imaging also have the potential to speed our basic 
understanding of the disease--for example, to determine which 
pathological features of AD (plaque and tangle development, cell death, 
loss of connections between neurons) best correlate with cognitive 
loss. Improved imaging techniques may further enable us to visualize 
the effects of therapeutic interventions more rapidly and accurately, 
with the potential for making AD clinical intervention trials smaller, 
faster and more affordable.
    Last year, we announced our plans for a Neuroimaging Initiative, a 
longitudinal, prospective, natural history study of normal aging, mild 
cognitive impairment, and early AD to evaluate neuroimaging techniques 
such as MRI and PET, as well as other biological markers. I am pleased 
to tell you that the Initiative is underway. Awards will be made this 
autumn, with work on the project to begin shortly thereafter. The study 
objectives are to:
     Identify the best markers for early diagnosis of AD.
     Identify markers for following disease progression and 
monitoring treatment response.
     Develop surrogate endpoints for clinical trials.
     Decrease time and expense of drug development.
     Establish methods for the collection, processing, and 
distribution of neuroimaging data in conjunction with other biological, 
clinical, and neuropsychological data.
    The initiative is planned as a partnership among the NIA/NIH, 
academic investigators, the pharmaceutical and imaging equipment 
industries, the Food and Drug Administration, the Centers for Medicare 
and Medicaid Services, and the NIH Foundation, with participation from 
the Alzheimer's Association and the Institute for the Study of Aging. 
The clinical, imaging, and biological data and samples will be made 
available, with appropriate safeguards to ensure participant privacy, 
to all scientific investigators in the academic and industrial research 
communities.

Prevention and Treatment

    There is currently no available treatment for AD that is highly 
effective for large numbers of patients, that maintains its 
effectiveness for a long period, that works in both early and late 
stages of the disease, that improves functioning of patients in 
activities of daily living as well as on sensitive neuropsychological 
measurements, and that has no serious side effects. In addition, none 
of the treatments presently approved for AD alter the progressive 
underlying pathology of the disease. In 2003, the Food and Drug 
Administration approved memantine (Namenda TM), the first drug to treat 
moderate to severe AD. Although memantine does not affect AD's 
underlying pathology, it can ameliorate symptoms of the disease. 
However, a wide variety of new treatments and approaches are emerging.
    As imaging and laboratory studies tell us more about AD's 
pathology, we are identifying a number of novel molecular 
characteristics that may prove to be targets for treating the disease 
or preventing it altogether. For example, enhancing the brain's self-
protective capacity by inducing production of naturally-occurring 
proteins that destroy beta amyloid shows promise in mice that have been 
genetically altered to produce amyloid plaques. In a recent study, 
boosting production of two proteins, insulin-degrading enzyme and 
neprilysin, in neurons of these mice reduced brain amyloid levels, 
slowed or even prevented amyloid plaque formation, and prevented the 
premature death of these mice. A similar approach--vaccination with a 
substance that directly attacks brain amyloid--continues to show some 
promise. Although a recent clinical trial was halted due to dangerous, 
treatment-related brain inflammation, we are hopeful that this line of 
research, which is being pursued by many investigators using related 
but alternative approaches, will ultimately yield a better, safer 
treatment.
    Promising clinical and basic research is also ongoing on 
complementary and alternative (CAM) approaches to treating AD. For 
example, the NIA, the National Institute of Neurological Disorders and 
Stroke, and the National Heart, Lung, and Blood Institute participate 
with the National Center for Complementary and Alternative Medicine 
(NCCAM) in the Ginkgo Evaluation of Memory (GEM) study, a multisite 
clinical trial of Ginkgo biloba for the prevention of AD in cognitively 
normal elders. Involving over 3,000 participants, the GEM study is the 
largest ongoing clinical trial of any botanical product. The NIA is 
also supporting a clinical trial of the effects of huperzine, a Chinese 
moss extract that may enhance memory and other cognitive functions by 
suppressing the activity of certain brain enzymes that are overactive 
in AD on progression of AD symptoms.
    Related research is ongoing to determine Ginkgo's mechanism of 
action. A recent trio of NCCAM-supported studies has suggested that a 
standardized Ginkgo extract could protect cells from oxidative stress 
and programmed cell death. These studies suggest that Ginkgo may 
provide protection to neural tissues, adding to the body of preliminary 
evidence from several small clinical studies that this botanical 
supplement could be beneficial in preventing the onset of dementia.
    In addition to these efforts, NCCAM supports a number of other AD-
related studies in model systems that are designed to understand the 
basic mechanisms by which dietary supplements may prevent or treat the 
symptoms of AD. For example, NCCAM is supporting investigations of the 
potential mechanisms of several traditional Asian medicines used to 
treat AD. Also, NCCAM is supporting a study on the use of high-
intensity light therapy for AD in patients in nursing homes to address 
the treatment of sleep/wake disorders, depressive symptoms, and 
agitation, among the most difficult long-term care management issues 
for people with AD.
    In the search for effective preventives and treatments for AD, 
animal models--particularly transgenic mice, but also flies, worms, 
dogs, and even nonhuman primates--are invaluable research resources for 
studying age-related and disease-related changes in the brain and for 
testing promising interventions. For example, investigators recently 
studied the effects of an enriched diet on age-related cognitive 
decline in dogs, a model that mimics the behavioral and brain 
pathological declines of older humans more closely than rodent models. 
Young and old dogs were given a series of baseline cognitive tests. 
Half of each age group then remained on a standard diet, while the 
other half of each age group was placed on a diet enriched with 
antioxidants and mitochondrial co-factors, which are thought to improve 
nerve cell energy and efficiency and decrease production of molecules 
that contribute to oxidative damage in the brain. Animals remained on 
their respective diets for 6 months and then were assessed again for 
cognitive performance on a variety of tasks. When tested, old dogs on 
the control diet learned more slowly than the young dogs and made 
significantly more errors; however, when compared to the old animals on 
the control diet, old animals on the enriched diet showed significantly 
better learning, although not to the level of the younger animals. The 
success of this simple, cost-effective intervention has significant 
implications for dietary interventions that might lessen or even 
prevent some of the cognitive decline seen with age and with disease; 
several clinical trials of antioxidants are currently underway.
    The NIA is currently supporting over 20 AD clinical trials, 
including large-scale prevention trials, which are testing agents such 
as hormones, anti-inflammatory drugs, statins, homocysteine-lowering 
vitamins, and anti-oxidants for their effects on slowing progress of 
the disease, delaying AD's onset, or preventing the disease altogether. 
Other intervention trials are assessing the effects of various 
compounds on the behavioral symptoms (agitation, aggression, and sleep 
disorders) of people with AD.

Caregiving

    Most of the over 4 million Americans with AD today are cared for 
outside the institutional setting by an adult child or in-law, a 
spouse, another relative, or a friend. Caregivers frequently experience 
significant emotional stress, physical strain, and financial burdens, 
yet they often do not receive adequate support for their remarkable 
efforts. Several recent studies have explored the problems faced by 
caregivers of AD patients, and have sought to design interventions to 
reduce their burdens. Although family caregiving has been extensively 
studied, there has been less research on the impact of end-of-patient-
life on caregivers who are family members of persons with dementia or 
to the caregivers' responses to the death of the patient. As part of 
the NIA's Resources for Enhancing Alzheimer's Caregiver Health (REACH) 
study, a multisite randomized clinical intervention of 1,222 caregiver 
and recipient dyads, investigators assessed the type and intensity of 
care provided by 217 family caregivers to persons with dementia during 
the year before the patient's death, as well as the caregivers' 
responses to the death. Additionally, this group was compared to the 
180 caregivers who institutionalized their family member. The 
researchers found that the in-home caregivers reported tremendous 
levels of stress in the year leading up to the care recipient's death, 
and that levels of caregiver depression ``spiked'' immediately 
following the care recipient death. However, the caregivers in this 
study demonstrated tremendous resilience: Within 15 weeks of the 
recipient's death, depression returned to pre-death levels, and within 
1 year, depression was significantly lower than prior to the care 
recipients' death. Importantly, caregiver depression for those placing 
their loved ones in an institution was slightly higher both pre- and 
postdeath than for those caring for the patient at home. These findings 
suggest that interventions for caregiver support are particularly 
critical in the periods immediately prior to and immediately after the 
patient's death.
    The NIA's REACH Project, a large, multisite intervention study of 
family caregivers of AD patients, was designed to characterize and test 
promising interventions for enhancing family caregiving. Nine different 
social and behavioral interventions were tested, and investigators 
found that the combined effect of certain interventions alleviated 
caregiver burden, and that certain specific interventions, such as 
structured family therapy, reduced depression. The second phase of the 
study, REACH II, combines elements of the most effective interventions 
tested in REACH into a single multicomponent psychosocial intervention 
and is ongoing.

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 Americans.
    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 Bond. Dr. Morris?
    Dr. Morris. Senator Bond, Senator Mikulski, thank you very 
much for the opportunity to appear here.
    I am a neurologist taking care of Alzheimer's patients and 
their families. I also direct the Alzheimer's Disease Research 
Center at Washington University in St. Louis, and I am a member 
of the national board of the Alzheimer's Association. So I have 
a variety of opportunities to interact with Alzheimer's on a 
daily basis.
    The Alzheimer's disease research centers were first funded 
in 1984, and in the past 20 years, the centers and related 
programs have learned a great deal about Alzheimer's disease.
    First, we now know that it is just that--it is a disease. 
It is not part of normal aging. As a disease, it can be 
diagnosed, and indeed we can diagnose Alzheimer's disease with 
high accuracy. We have learned even to extend the diagnosis to 
the initial symptomatic stages, sometimes even in the mild 
cognitive impairment stage.
    So it can be recognized and accurately diagnosed very 
early. Unfortunately, many people are unaware of this and still 
believe that Alzheimer's disease is inevitable with age, it is 
part of the aging process, and even though the diagnostic 
opportunities are there to recognize it, many physicians and 
many families are unaware of this.
    As a matter of fact, Alzheimer's disease is woefully 
underdiagnosed in the United States, even with our accurate 
diagnostic tools. The tragedy of that is that without 
recognizing it, it is woefully undertreated. We do have 
treatments available to help the symptoms of Alzheimer's 
disease. Alzheimer's disease is a treatable disorder. So we 
need to get the word out to better recognize it and to better 
treat the symptoms.
    Now, it is true that the current therapies only help the 
symptoms, and only for a limited time. So the vast majority of 
research is interested in looking at interventions that will 
help the very brain changes that cause the disease--
interventions to affect the disease process, to arrest it, and 
hopefully even to prevent it.
    But to do that, we need to understand the disease process 
even before symptoms appear. It is very likely--very likely--
that Alzheimer's disease changes begin in the brain years or 
even decades before any dementia appears. It is possible that 
the illness begins in middle age or even earlier. And if we 
ever want to prevent the disease, we have to recognize those 
brain changes at the asymptomatic stage and intervene there to 
prevent the occurrence of dementia symptoms from appearing.
    There are very exciting, very innovative medications that 
potentially have the promise of intervening at that early 
stage, and as Dr. Hodes indicated with his imaging work, in 
fact there may be opportunities to detect the disease in the 
pre-symptomatic stage.
    Much research is focused upon this effort. For example, at 
our Alzheimer's center, we have inaugurated an adult children 
study with children whose parents had Alzheimer's disease, who 
are participating in all of these research ventures to see what 
are the earliest changes that may occur so that when these 
disease-modifying therapies are available, we know with whom to 
intervene at the most opportune time.
    Unfortunately, with the budget slowdown, these and other 
research efforts are having to be truncated. It is a remarkable 
time in Alzheimer's disease research. The past 20 years have 
yielded remarkable advances, and in addition, they have 
provided us with the research infrastructure to test all of 
these new opportunities and new hypotheses. We have the 
investigators, we have the research participants, we have the 
drugs, we have the desire to see if we can arrest or cure 
Alzheimer's disease.
    So this is the time to take advantage of all the investment 
of the past 20 years. Unfortunately, some of these initiatives 
are going to have to be truncated if we do not continue to 
invest in trying to develop a world without Alzheimer's 
disease.
    Thank you very much.
    Senator Bond. Thank you, Dr. Morris.
    [The prepared statement of Dr. Morris follows:]
               Prepared Statement of John C. Morris, M.D.
    The rapidly growing older adult population has resulted in dramatic 
increases in age-associated illnesses, most notably the dementing 
disorders. Dementia affects 10 percent of all individuals 65 years or 
older, and its prevalence rises exponentially to approach 50 percent by 
age 85. Dementia is costly, both in terms of public health burden ($100 
billion annually in the U.S.) and in the personal toll extracted from 
patients and their families. As U.S. society continues to age, the 
already major impact of dementia soon will become overwhelming unless 
effective interventions become available.
    There have been remarkable clinical and research advances in 
dementia in the past 2 decades. It is now appreciated that dementia is 
not part of normal aging but instead represents a disease process. 
Although a diagnostic test or biomarker is lacking for most dementing 
disorders, clinical diagnosis can be surprisingly accurate. Most 
importantly, effective therapeutic options are now available for 
Alzheimer disease (AD), by far the most common cause of dementia--AD 
now is a treatable disorder! The availability of treatments has led to 
improved detection of dementia in its earliest stages and stimulated 
great interest in prodromal conditions, such as mild cognitive 
impairment.
    Currently approved drugs provide symptomatic benefit for AD. 
Although the effect size is modest, their benefit is appreciated by 
physicians and families and can be demonstrated for periods extending 
beyond 1 year. Many other agents are being tested in clinical trials. 
Recent drug development efforts are directed toward disease-modifying 
strategies. Should one or more of these approaches prove safe and 
effective, it may become possible to arrest the progression of AD or 
even to prevent its occurrence.
    The optimal time to initiate prevention strategies is in the latent 
or preclinical stages of AD, prior to the occurrence of any symptoms. 
It is possible that Alzheimer's begins in the brain years or even 
decades before sufficient damage occurs to allow dementia symptoms to 
be expressed. Because the diagnosis of AD currently depends on these 
symptoms, detection of the preclinical stages is not possible at 
present. However, highly promising new strategies, including 
identifying Alzheimer brain changes with imaging techniques in 
asymptomatic persons, now are under investigation. A very reasonable 
prediction is that, in the not too distant future, persons at risk for 
developing AD because of family history or other factors can be 
assessed before symptoms appear. If they have suggestive brain changes, 
ideally they would be offered therapies that prevent the development of 
dementia!
    This is a propitious time to pursue the tremendous opportunities 
for the effective treatment, prevention, and even cure of AD. The 
appropriate infrastructure is in place with ample numbers of patients, 
investigators, and assessment tools to test the many promising 
therapeutic agents now being developed. The only limiting factor is a 
lack of funds to carry out these innovative research studies that hold 
potentially enormous consequences for patients and for society.

    Senator Bond. Dr. Rabins?
    Dr. Rabins. Thank you, Senator Bond, Senator Mikulski.
    I would like to address the currently available treatments, 
the potential for prevention, and where I see the future in 
Alzheimer's disease research.
    Right now, there are two classes of medicines that are used 
to treat Alzheimer's disease, and both of these classes 
actually depend on breakthroughs that were made back in the 
1970's. In the early 1970's in this country and in England, it 
was discovered that individuals dying with Alzheimer's disease 
have a deficiency of a particular chemical called acetylcholine 
in their brains. Three of the medicines that are widely used 
now to treat Alzheimer's disease all work by increasing the 
amount of that chemical.
    The second class of medicines that is now used to treat 
Alzheimer's disease also derives from breakthroughs in the 
1970's, both at Washington University and Johns Hopkins. This 
research showed that when the cells that make chemicals like 
acetylcholine do not make enough, the receiving cells send a 
message back saying: Send more, send more. That is, they excite 
the other cell. Unfortunately, when they do not get enough, 
they overexcite the cell to the point where they actually cause 
death. So the body's attempt to recover from a lack of this 
acetylcholine chemical actually causes overexcitement of these 
remaining cells and then leads to death. So the second class of 
medicines, the first one of which was just recently approved by 
the FDA, works by dampening how the body tries to restimulate 
it.
    So those are the two classes of medications, both depending 
on research breakthroughs from the 1970's.
    I think what is exciting, as Dr. Hodes said, is that what 
has happened in the last 20 years is that we now understand, we 
think, what is actually happening inside the brains of people 
with Alzheimer's disease. The leading theory of the cause is 
that abnormal proteins are being deposited in the brain. And I 
think what is very exciting now--and I would like to take Dr. 
Morris' use of the word ``remarkable''--is that the 
opportunities that we have now are to interfere with the 
deposition of these abnormal proteins in such a way that 
perhaps they could be removed from the brain or at least the 
deposition could be slowed down or prevented. We are at a point 
in time when there are many different opportunities, and a 
number of biotech companies, pharmaceutical companies, but a 
lot of this work is so basic that it really depends on NIH 
funding, and I think we are at a crucial point where many of 
these new opportunities will not be followed through, such as 
chelation therapy for some of the ions and metals that may be 
involved--that we will lose those opportunities for developing 
treatments.
    As far as prevention, we are also at an exciting time, and 
I would just like to very briefly highlight four potential 
prevention strategies.
    The first, as Dr. Hodes mentioned, it is clear now that the 
risk factors for cardiovascular disease--that is, high blood 
pressure, high cholesterol, obesity, and diabetes--when those 
appear to be aggressively treated, it appears that we can 
actually decrease the likelihood of developing Alzheimer's 
disease. So in that way, we have opportunities now to begin 
with prevention.
    A second intriguing area is that many studies have 
suggested that drugs like Motrin, nonsteroidal anti-
inflammatory drugs, may be preventive, and there is a very 
large trial funded by the National Institute on Aging that is 
looking at whether taking several of these medications might 
actually delay the onset of Alzheimer's disease. So we will 
have an answer to that in several years.
    I think, as Dr. Hodes also mentioned, the area of genetics 
is extremely important. People tend to think of genetics as 
something that we will not be able to change, but with a 
disease like Alzheimer's disease that does not begin for 50, 
60, or 70 years, if we could understand the genetics of this 
illness, that would offer us actual opportunities to develop 
drugs and other preventive strategies even if you carry a 
genetic risk factor. So I think that is very exciting.
    Then, the fourth area, which builds on something that 
Senator Mikulski mentioned, is the whole issue of whether 
exercise, physical exercise, and mental activity might be able 
to delay the onset of Alzheimer's disease, and there are a 
number of studies that suggest that possibility. I think the 
need for further trials in that area is important.
    I think we are at the crucial point now in the development 
of treatments and preventions, and I think that with further 
funding, the possibility of a breakthrough that will diminish 
both the burden of family and this tremendous financial burden 
is great.
    Senator Bond. Thank you very much, Dr. Rabins.
    [The prepared statement of Dr. Rabins follows:]
              Prepared Statement of Peter V. Rabins, M.D.
    Honorable Senators and other attendees. In my testimony I will 
address the availability and adequacy of current treatments for 
Alzheimer disease, the potential for preventing Alzheimer disease and 
the importance of continued support for research and care into this 
devastating, common illness.
    Descriptions of Alzheimer disease are contained in the earliest 
medical writings that are 3,000 years old. However, the brain changes 
characteristic of Alzheimer disease were described only 100 years ago 
and it has only been in the past 35 years that clinicians, scientists 
and the public have appreciated the fact that what used to be called 
``senility'' is a group of diseases referred to medically as dementias. 
Today we recognize that two-thirds of all cases of late life dementing 
is caused by Alzheimer disease.
                     currently available treatments
    The recognition that ``senility'' is most commonly caused by 
Alzheimer disease led to the discovery in the mid-1970s by researchers 
in Europe and the United States that a chemical called acetylcholine is 
deficient in the brains of individuals dying from the illness. Three of 
the treatments that are available today, donepezil (Aricept), 
galantamine (Reminyl) and rivastigmine (Excelon) work by increasing the 
amount of this chemical in the brain. These medications are all 
modestly effective in treating patients with Alzheimer disease; this 
benefit translates into improved function, behavior and cognition 
(thinking). On average, these drugs bring about a 6-9 month improvement 
in the disease. However, they do not modify the underlying biology; the 
death of brain cells due to the disorder continues in spite of 
treatment. It is important to emphasize that the modest benefit 
provided by these medications translates into meaningful improvement 
and, equally importantly, demonstrates that the symptoms of the disease 
are amenable to biological therapies.
    A second class of medications builds upon the discovery made at 
Washington University, St. Louis and Johns Hopkins that the brain 
responds to loss of acetylcholine by stimulating or ``exciting'' the 
remaining cells with the neurotransmitter glutamate. Unfortunately, 
this results in ``excito-toxicity'' due to overstimulation of these 
remaining cells. The first example of this class of medications, 
memantine, (Namenda) was developed in Germany and recently approved by 
the FDA for the treatment of individuals with moderate-severe 
Alzheimer. It is hoped that disease progression might be slowed by 
blocking glutamate but this has not yet been proven.
                          POTENTIAL TREATMENTS
    Tremendous strides have been made in the past 25 years in 
understanding the basic biology of memory and other thinking processes. 
Drugs are under development that seek to enhance these processes. In 
addition, an extensive body of research has focused on the function and 
metabolism of the proteins thought to be involved in the genesis of 
Alzheimer disease. Studies funded by the NIA, NINDS and NIMH suggest 
that the deposition of abnormal proteins may be the initiating and/or 
perpetuating cause of Alzheimer disease. Many pharmaceutical companies, 
biotech companies and publicly funded researchers are studying 
compounds that potentially interfere with the formation or deposition 
of these abnormal proteins, or might increase their removal from the 
brain. Studies of the effectiveness of these therapies has begun only 
recently, but the quality of research being performed now is quite 
extraordinary and many scientists believe that therapies that target 
the biology of the disease and slow its development, stop its 
development or reverse the abnormalities are a possibility. NIH-
sponsored research has played a major role in the development of many 
of these approaches.
                               TREATMENT
    Extensive nondrug research demonstrates the benefit of 
interventions that provide information and emotional support to 
caregivers. Intriguingly, these interventions have been shown to have 3 
benefits, improving the psychological well-being of the caregiver, 
diminishing the prevalence of behavioral and psychiatric symptoms in 
the patient and delaying placement in a long-term care facility, a goal 
of many family members and patients. Much of this research has been 
supported by the NIH.
                               PREVENTION
    At present, the best supported preventive strategy for Alzheimer 
disease is treating the risk factors for brain vascular disease--
controlling high blood pressure, elevated cholesterol, elevated low 
density level lipoprotein (LDL) levels, diabetes and obesity. The 
contribution of these to the development of Alzheimer disease may be 
modest but they could have a meaningful impact because so many people 
are affected.
    A second potential prevention strategy is the use of nonsteroidal 
anti-inflammatory drugs (NSAIDS) such as ibuprofen (Motrin, Advil and 
generic). At present, the studies supporting the preventive actions of 
the drugs in this class are all retrospective. That is, they depend on 
data collected from individuals who do have Alzheimer disease and do 
not have Alzheimer disease. A prospective trial (funded by the NIA) 
called ADAPT should tell us in several years whether drugs in this 
class can delay the onset or prevent Alzheimer disease. It now appears 
that women who take hormone replacement therapy after age 64 are at 
increased risk of developing Alzheimer disease. However, some research 
suggests that estrogen taken at the time of menopause may be 
preventive. More research is needed on this topic.
    A third area of research that has potential for prevention is the 
study of genetic risk factors. This may reveal targets for medication 
that can prevent or delay the onset of disease.
    A fourth area of intense interest and scrutiny is whether mental 
and/or physical activity lowers the risk of developing Alzheimer 
disease. To date, studies supporting this are all retrospective and 
thus can only suggest the possibility of such a benefit. Some research 
also suggests that more years of education offers some protection and 
some individuals raise the possibility that this may work by increasing 
connections among brain cells.
                            FUTURE PROSPECTS
    In my opinion we are at a crucial point in the development of 
therapies aimed at altering the biology of Alzheimer disease. Whether 
such a treatment will be available in 5 years or 50 years cannot be 
foreseen, but the pace of research and the advances already made 
increase the likelihood that a disease-altering or preventing therapy 
will be identified. In my opinion, the need or continued research in 
this area should remain a high priority, given the devastation wrought 
by this illness on individual Americans and their family members as 
well as the economic costs of the disease. In many States, Medicaid 
nursing home benefits are one of the largest individual budget items 
and Alzheimer disease is the single greatest contributor to nursing 
home placement in the U.S.
    Research should also continue to look for better strategies to 
diminish the emotional, financial and behavioral burdens wrought by the 
dementias until cures and preventions are available. This important 
work complements research into the basic biology of the disease and the 
development of more biological effects therapies.
    As a clinician and clinical researcher for 30 years, I have watched 
Alzheimer disease change from a condition known to a handful of experts 
to a disorder that is feared universally. Only through continued 
research can these fears and burdens be relieved. The need for such 
research is shown in a study that I have just completed which 
demonstrates that fewer than \1/3\ of people with Alzheimer disease who 
live at home are recognized by their doctor as having dementia.

    Senator Bond. Mr. McConnell?
    Mr. McConnell. Senator Bond, Senator Mikulski, thank you 
for inviting the Alzheimer's Association to this hearing.
    This is a very important topic that comes at a critical 
time. You both pointed out this epidemic, really, of 4.5 
million now, growing to as many as 16 million. There is a new 
Neurology Journal study coming out today showing the increases 
by State, an 18 percent increase in the next 20 years in 
Missouri and a 25 percent increase in Maryland during that 
period of time.
    The impact on Medicaid and Medicare is enormous. The cost 
for just treating Alzheimer's disease in Medicare will go up 55 
percent in this decade to $50 billion, and for Medicaid, an 
increase of 80 percent to $33 billion. That is just for 
treating Alzheimer's disease. So this is not just a matter of a 
science question; it is a matter of public health and huge 
impact on Federal programs.
    Having said that, there is an enormous amount of hope. You 
have heard that from the scientists to my left. And we are 
trying to get that message out to the public. The Alzheimer's 
Association has launched a Maintain Your Brain Campaign--I have 
a brochure here; the ink is still drying on it--taking what we 
have learned in science and trying to get it out to, for one 
thing, the 78 million baby boomers who are living in denial. 
That is my age cohort, and the baby boomers say this is an 
issue that we cannot do anything about, it is inevitable, and 
we are going to turn off to it.
    So we are trying to say no--there is an enormous amount 
that can be done. Dr. Rabins has talked about it; all of the 
scientists here have talked about it.
    No. 1, we say manage your numbers. As Dr. Rabins pointed 
out, the linkage between cardiovascular disease and Alzheimer's 
disease is becoming clearer. Keep your blood pressure under 
control, your cholesterol, your blood sugar, your body weight. 
We do not know that those will prevent Alzheimer's disease, but 
they cannot hurt, and there is some evidence that it may help 
in preventing Alzheimer's.
    Second, feed your brain--a multivitamin with folic acid, 
vitamin E, vitamin C. Eat foods right in Omega-3 fatty acids.
    Third, exercise your body and brain by working out, taking 
a class, reading, playing cards. I love the study that came out 
recently that shows that dancing may actually be preventive--
and I suspect that is only if you are a good dancer--but 
nonetheless, these are simple things that are about keeping 
your heart and your body healthy that may keep your brain 
healthy.
    But the public does not understand this and still thinks 
there is not much that can be done.
    All of this progress has been made because of your efforts 
to double the NIH funding, which has also doubled research 
funding for Alzheimer's disease. That is now starting to taper 
off, and we are already starting to see a tapering off in what 
NIA can fund. They can fund fewer grants; they have to fund 
them at a smaller level. There are research projects at UC-San 
Diego on combination therapies that will not go forward because 
there is not enough funding.
    So the Alzheimer's Association is asking for a modest 
increase of $40 million to the $670 million a year that is 
being spent on Alzheimer's disease so we can keep this progress 
going. Otherwise, our investment will be for naught.
    I do want to point out the second part of our mission and 
also of this hearing is on caregiving. The Alzheimer's 
Association is committed to helping families and people with 
this disease through our chapters. We have a 24/7 contact 
center; people can call in the middle of the night if they are 
having a crisis and get help. We have clinical social workers 
on that line, and that is also being supported in part by your 
efforts and appropriations.
    We know that caregiving particularly for people with 
Alzheimer's disease is enormously stressful. There are greater 
stress-related illnesses and even higher mortality rates 
because of caregiving for Alzheimer's disease. So we need to 
help families, and I particularly want to acknowledge, Senator 
Mikulski, your bill, the Family Caregiver Relief Act of 2003, 
the $5,000 tax credit. That not only will help people by 
providing them with resources, but it legitimizes caregiving. 
People are out there struggling with this stuff by themselves, 
and in this case, if there is a tax credit, it says, you know, 
this is an important enough issue that the Government cares 
enough about it to give us a tax credit, it helps people 
psychologically and otherwise.
    The Alzheimer's Disease Research, Prevention, and Care Act 
of 2003, the Alzheimer's Demonstration Grants, which are 
leading the way in finding ways to deliver services, 
particularly respite and home and community-based services, to 
underserved communities. There is a project in Missouri, and 
there is a project in Maryland under this grant, and it is 
producing terrific results.
    So we have to keep going forward on the research front. We 
need to make sure that the information gets out to the public, 
and hearings like this can help educate people on what needs to 
be done. But if we do not have the funding to keep this 
progress moving--just for example, the ginkgo biloba trial that 
was mentioned by Dr. Hodes is $30 million to do that one trial. 
So if we can only do one trial at a time and wait to see the 
results, we will not get this problem taken care of before that 
baby boom population hits the age of highest risk.
    So again, there is enormous hope, more and more help for 
caregivers, but we are still on the cusp of those major 
breakthroughs, and the Alzheimer's Association is very 
optimistic. We do our part--we have committed $150 million to 
this research effort--and we thank you for all that you are 
doing.
    [The prepared statement of Mr. McConnell follows:]
                Prepared Statement of Stephen McConnell
    Good morning Senator Bond and Senator Mikulski. Thank you for 
inviting me to discuss the Alzheimer's Association's legislative 
priorities as well as our exciting new ``Maintain Your Brain'' 
initiative. I want to acknowledge the outstanding leadership that both 
of you have provided in the fight against Alzheimer's disease. The 
Alzheimer's Association especially appreciates your commitment and 
dedication to improving care and services for individuals with 
Alzheimer's disease and their caregivers. We thank you for introducing 
S. 566, the Alzheimer's Disease Research, Prevention & Care Act, 
legislation to renew a highly successful program that is providing 
Federal grants to States to develop innovative models of care for 
persons with Alzheimer's disease. In addition, we are indebted to 
Senator Mikulski and other Members of this Subcommittee who are 
cosponsoring S. 538, the Lifespan Respite Care Act, and S. 1214, the 
Family Caregiver Relief Act, proposals to increase the availability of 
respite care services and create a tax credit for family caregivers.
    Since our founding in 1980, the Alzheimer's Association has 
provided more than $150 million to support research into the 
prevention, treatment and eventual cure for Alzheimer's. Our nationwide 
network of chapters offer frontline support to individuals affected by 
Alzheimer's with services that include 24/7 information and referral, 
safety services, and education and support groups. In addition, we are 
partnering with over 150 local, State and national organizations 
representing more than 50 million Americans on our ``Coalition of 
Hope'', the largest Coalition ever formed in support of research to 
find new treatments for individuals with Alzheimer's disease. The 
Coalition of Hope includes groups well known in the aging field, 
including AARP, the Older Women's League and the National Association 
of Retired Federal Employees. It also includes other organizations like 
the Urban League, the Polish American Congress, the NAACP and the Sons 
of Italy, who know that Alzheimer's touches so many families and 
communities, in small towns and big cities all across the country.
    The mission of the Alzheimer's Association, working in partnership 
with government and private industry, is to eradicate this disease and 
to provide support to improve quality of life for those facing the 
disease now. Through the combined efforts of the Association, the 
National Institutes of Health, and the pharmaceutical industry, 
advances in medical treatment have surged forward in recent years. The 
Alzheimer's Association's goal of delaying the disabling symptoms of 
Alzheimer's disease, and eventually preventing the disease now appears 
possible. For the first time, creating ``A World Without Alzheimer's'' 
is within reach. We can go to the American people now with a new 
message of hope. We can--we will--have a future where Alzheimer's 
disease is only a memory.
    This hearing comes at a critical time. With the aging of the baby 
boomers, the number of people with Alzheimer's will grow from 4.5 
million today to an astounding 11 to 16 million by the middle of the 
century. Today's issue of Neurology features a new study estimating 
state-specific projections of the prevalence of Alzheimer's disease 
through 2025. Although the study found that the greatest rates of 
growth in the number of cases of Alzheimer's disease will be seen in 
the Southern and Western regions of the country, few States will be 
spared from the impact of Alzheimer's disease. Missouri will see an 18 
percent increase in the number of cases of Alzheimer's disease. 
Maryland faces an even greater rate of growth--28 percent by 2025. Left 
unchecked, Alzheimer's will undermine our families, communities, and 
basic economic security. It will overwhelm our health care system, 
bankrupt Medicare and Medicaid, drain billions of dollars from American 
business, and destroy retirement security for tens of millions of 
families. The cost to Medicare will go up 55 percent to $50 billion in 
less than 10 years and the cost to Medicaid will soar by 80 percent to 
$33 billion. The costs to families and caregivers will go even higher.
    We can treat Alzheimer's and some day we may be able to prevent 
this disease, but not without more funds for research and greater help 
from Congress. If the current pace and momentum of research is 
maintained we may be able to delay the onset and progression of 
Alzheimer's, saving not only billions of dollars to our health care 
system but also saving millions of lives. This is not the time to tell 
the scientists to slow down. But this is exactly what will happen 
unless we continue to expand the public investment in Alzheimer 
research.
News You Can Use: The Maintain Your Brain TM Campaign
    The title of this hearing, ``Breakthroughs in Alzheimer's Research: 
News You Can Use'' is particularly relevant to an effort underway to 
change the way Americans think about Alzheimer's disease. Thanks to the 
rapid progress being made in understanding, diagnosing and treating 
Alzheimer's disease, we can share the news that Alzheimer's disease is 
not an inevitable part of aging. Earlier this year, the Alzheimer's 
Association launched a new Maintain Your Brain TM campaign to let the 
public know that a world without Alzheimer's disease can be a reality, 
to encourage Americans to take steps now to take care of their brain 
and to engage more people in advocacy for research, new treatments and 
improved care.
    The Maintain Your Brain TM campaign is targeted to the 77 million 
American baby boomers to encourage them--I should say ``us''--to get 
involved. To date, baby boomers have largely ignored Alzheimer's 
disease because they don't think there is anything you can do about it. 
Our campaign is designed to change that before we enter the age of 
greatest risk for dementia. If we are successful, we may be able to 
avoid some of the devastating problems that are looming on the horizon.
    Our Maintain Your Brain Campaign is based on the mounting evidence 
that we can manage certain risk factors and maintain optimal brain 
functions. Just as we can take steps to preserve a healthy heart, we 
can manage certain risk factors to maintain a healthy brain. Manage 
your numbers--blood pressure, cholesterol, blood sugar and body 
weight--to stay healthy as you age. Feed your brain by taking a 
multivitamin that includes folic acid, vitamins E and C and eat foods 
rich in omega-3 fatty acids. Exercise both your body and brain by 
working out, taking a class, reading, playing cards or working on 
crossword puzzles. Know that the joint efforts of government agencies, 
research centers and pharmaceutical companies have uncovered many of 
the secrets of Alzheimer's disease and that there are many reasons to 
be hopeful. And, perhaps most importantly, get involved in advocacy for 
more research, improved treatments, and better care.
The Alzheimer Research Agenda
    Most scientists believe that discovering effective methods and 
treatments that will delay the onset and progression of Alzheimer's as 
well as prevent the disease are well within reach in the foreseeable 
future if the current pace and momentum of research is maintained. 
Research supported by the National Institutes of Health needs $40 
million in additional funding this fiscal year alone to carry out large 
scale, controlled, clinical trials that will identify therapies and 
treatments capable of slowing or halting the onset and progression of 
Alzheimer's. Basic research has produced positive discoveries, but we 
need to know whether the discoveries will actually work. Clinical 
trials are the only way to translate--and verify--the findings of basic 
research into real-world treatments. A single large-scale clinical 
trial could cost as much as $25 million and take 3 to 5 years. The 
Alzheimer's Association is asking Congress to increase funding for 
Alzheimer research by $40 million for fiscal year 2005 to fund large-
scale clinical trials to test the effectiveness of vitamins and other 
treatments that would slow or delay the progression of Alzheimer's.
    While we maintain hope about our ability to slow the progression of 
and 1 day prevent Alzheimer's disease, we must also invest in research 
that will speed the discovery of risk factor genes for late-onset 
Alzheimer's, the most common form of the disease. Discovery of risk 
factor genes will help illuminate the underlying disease processes of 
Alzheimer's disease, open up novel areas of research and identify new 
targets for drug therapy. The National Institute on Aging (NIA) and the 
Alzheimer's Association are in the process of recruiting at least 1,000 
families over the next 3 years to create the Nation's largest 
repository of genetic material from families affected by late-onset 
Alzheimer's disease.
    The National Institute on Aging, in partnership with the 
pharmaceutical industry, the Alzheimer's Association and the FDA, is 
also engaged in a new initiative using imaging technologies to monitor 
changes in the brain that indicate progression of Alzheimer's disease 
and to provide accurate, earlier diagnosis. We are hopeful that this 
initiative will lead to better diagnostic techniques. More importantly, 
the imaging initiative may help speed up the process of discovering 
new, more effective treatments and preventive agents for Alzheimer's 
disease by allowing scientists to detect the effects of interventions 
on brain function much more quickly than traditional clinical trials 
without the use of imaging. The full participation of the 
pharmaceutical industry and the FDA will ensure that we gain maximum 
effect from this important initiative.
Supporting A Public/Private Partnership
    The Alzheimer's Association is the largest private funder of 
Alzheimer research, next to the pharmaceutical industry. As our 
commitment to research has grown, we have expanded the program to 
support Alzheimer researchers at every stage in their career. Projects 
supported by the Alzheimer's Association research program now explore 
the broadest possible spectrum of biological approaches to 
understanding, preventing, and treating Alzheimer's. In addition to our 
support of medical research, the Association also invests in improving 
care, with research grants supporting efforts to develop innovative 
social and behavioral strategies for managing the symptoms of the 
disease and improving quality of life, approaches to caregiving and 
improved understanding of caregiver issues.
    Our goal is to support research that complements the programs of 
the National Institute on Aging (NIA) and other centers of the National 
Institutes of Health (NIH). Our research program is designed to serve 
as an incubator for innovative ideas that can be further enhanced by 
the tremendous resources only available through NIH and its national 
network of Alzheimer's Disease Centers.
    Many of this country's premier Alzheimer researchers got their 
start with funds from the Alzheimer's Association. Alzheimer 
researchers funded by the Association have gone on to acquire major 
Federal funding, originate and advocate for important areas of 
research, train the next generation of scientists, establish many of 
the Alzheimer's Disease Research Centers and direct key programs at 
NIA. These researchers include brilliant scientists such as Dennis 
Selkoe, whose early work on amyloid proteins helped define our current 
understanding of Alzheimer's disease, Caleb Finch, who is the director 
of the Alzheimer's Disease Research Center at the University of 
Southern California, Gary Small, a leader in the imaging field and 
Marcelle Morrison Bogorad, who as an integral part of Dr. Hodes' team, 
directs the Neuroscience and Neuropsychology of Aging Program at NIA.
    In addition to partnering with NIA and other centers at NIH, the 
Alzheimer's Association also plays a major role in bringing the 
Alzheimer research community together for scientific meetings. In July 
we will present the ninth annual International Conference on 
Alzheimer's Disease and Related Disorders, the world's leading forum on 
dementia research. The International Conference serves as a catalyst 
for generating new knowledge about dementia and fostering a vital, 
collegial research community. Approximately 4,500 researchers, double 
the number who attended the July 2000 meeting in Washington, will 
gather in Philadelphia to share groundbreaking information and 
resources on the etiology, pathology and treatment of Alzheimer's 
disease and related disorders. The program will include 135 invited 
speakers, who are respected leaders and new voices in their 
disciplines, and more than 2,000 oral and poster presentations on 
current research. The conference also provides a significant 
opportunity to educate the public about breakthroughs in Alzheimer 
treatment and care.
A Roadblock to Progress
    All of the hope we have for a future without Alzheimer's disease 
will come to a crashing halt if we cannot maintain the current pace and 
momentum of funding for Alzheimer research. Only Congress and the 
President, through a significant addition of new funding, can assure 
that we realize the unprecedented opportunities in Alzheimer research. 
Minimal increases in funding for the NIH are not enough to support 
additional clinical trials and maintain the pipeline of basic 
scientific discovery. Failure to provide the funding increases that 
will help keep pace with inflation will destroy the momentum gained 
over the past 5 years. Inadequate funding increases mean that less 
money will be available to support new research grants and clinical 
trials, delaying scientific discoveries and resulting in lost 
opportunities.
    Although I am not a scientist, I have spent a lot of time talking 
with scientists. Let me give you just a few examples of the 
opportunities we will miss if we stick with current and proposed 
funding levels:
     Thanks to Congress' investment in NIH, the best scientists 
in the world are chomping at the Alzheimer bit--and that means NIA is 
receiving record numbers of applications. But at current budgets, they 
will be able to fund only about 15 percent of those proposals--far less 
than the 20--25 percent of past years. And they can only do that much 
by cutting one of every five dollars out of the successful grants. 
Think about how many scientific opportunities we are missing.
     What about the large scale clinical trials in which 
Congress has invested billions of dollars? After all, research doesn't 
mean a lot in the real world until we are successful in getting science 
from the bench to the bedside.
     Scientists at the University of California in San Diego 
are poised to start the next big trial of combinations of anti-
oxidants. This offers one of the most exciting possibilities for a safe 
and relatively inexpensive way to protect against Alzheimer's. But NIA 
does not have the money to get it started.
     Even trials that are well underway--like the ginko biloba 
trial being conducted through a collaborative effort between NIA and 
NCCAM--will have to be slowed down. There may be no money to analyze 
the data that has already been collected on the hundreds of volunteers 
who have participated in this trial.
     NIA currently funds 29 Alzheimer's Disease Research 
Centers, a program that has created the infrastructure for 
multidisciplinary collaborative research on the disease. NIA has seen 
an increasing number of applications from academic institutions seeking 
to create such centers and there are still parts of the country where 
Centers do not exist. Limited funding will make the competition for 
center grants especially tough this year. At the same time, we have 
heard that existing centers are increasingly strapped for funds to 
carry out their broad mission.
    This is a travesty. We cannot let it happen. We know that Congress 
faces many competing priorities, with very little discretionary money 
in the budget. We understand that, after doubling the NIH budget, there 
are those who are ready to say, ``we've done enough.'' But if we slow 
down now, we will be throwing away much of the investment the American 
taxpayers have already made in Alzheimer research. We must continue, 
and build on, the progress of the last 20 years. That is why we are 
asking you to increase funding for Alzheimer research by $40 million 
for fiscal year 2005. This is a modest request, given the urgency of 
the Alzheimer crisis and the enormity of the scientific opportunities. 
But it would be enough to sustain the momentum in tough budget times. 
The Neurology study on the growth in the prevalence of Alzheimer's 
disease by State that I cited earlier provides further evidence of the 
need to invest in the research that will help prevent or delay the 
onset of Alzheimer's disease. The study found that five States (Utah, 
Alaska, Colorado, Wyoming and Nevada) will see their total number of 
cases of Alzheimer's disease more than double between 2000 and 2025. 
The three largest States will also experience big increases in the 
number of cases of Alzheimer's disease--California faces a 50 percent 
increase, Florida a 64 percent increase and Texas a 74 percent 
increase. The best way to ensure that these estimates do not come true 
is to find an effective method of preventing Alzheimer's disease.
Taking Care of People With Alzheimer's & Their Caregivers: Social & 
        Behavioral Research
    One of the greatest challenges in Alzheimer's disease research is 
the translation of knowledge and technology from laboratory and 
research settings into everyday practical care situations with the goal 
of improving the quality of life for affected people, their families 
and care providers. Often, lack of knowledge about what constitutes the 
most important or ``active'' ingredient in a successful intervention 
hinders transporting the technique to usual care settings. There is a 
huge range of questions in the social and behavioral arenas that are 
ripe for research. The answers to these questions, if broadly applied, 
would improve the daily lives of millions of people with Alzheimer's 
disease and their families.
    The Alzheimer's Association has made improving the quality of care 
for persons with Alzheimer's disease and expanding access to home and 
community based services top priorities. In addition, we must find ways 
to support family caregivers who continue to be the backbone of the 
long-term care system in this country. Seven in ten people with 
Alzheimer's disease live at home. The estimated annual value of the 
informal caregiving system is $257 billion, far more than the $32 
billion cost of paid home health care and the $92 billion cost of 
nursing home care. The Association has endorsed several pieces of 
pending legislation that will help us achieve these goals including:
     S. 566, the Alzheimer's Disease Research, Prevention, and 
Care Act of 2003--cosponsored by the Chair and Ranking Member as well 
as several Members of this Subcommittee, this bill would reauthorize 
the highly successful Administration on Aging Alzheimer's Disease 
Demonstration Grants to the States Program. Thirty-nine States, 
including both Maryland and Missouri are participating in this unique 
program that is fostering the development of innovative models of care 
for persons with Alzheimer's disease and their caregivers, especially 
those in rural and low-income communities.
     S. 1214, the Family Caregiver Relief Act of 2003--
sponsored by Senator Mikulski, as well as other Members of this 
Subcommittee, this bill would provide a $3,000 tax credit to help 
family caregivers with long-term care expenses such as adult day care 
and respite care.
     S. 538, the Lifespan Respite Care Act of 2003--introduced 
by Senator Clinton of this subcommittee and co-sponsored by Senators 
Mikulski, Warner and Murray, this bill would increase the availability 
of respite care services and provide training for respite care workers 
and volunteers.
Conclusion
    There is now real hope for a future without Alzheimer's disease. 
Greater understanding of the disease, improved care and treatment, and 
unprecedented scientific opportunities for delaying onset and 
preventing the disease can all lead to a future where Alzheimer's is 
just a memory. Imagine the billions in savings to Medicare and Medicaid 
if scientists were able to develop a presymptomatic diagnostic 
technique and a preventive therapy that did not allow the disease to 
occur. But none of this will happen if we do not take action. Research 
supported by the National Institutes of Health needs $40 million in 
additional funding in this fiscal year alone to carry out large scale, 
controlled, clinical trials that will identify therapies and treatments 
capable of slowing or halting the onset and progression of Alzheimer's. 
Basic research has produced breakthroughs in our understanding of 
Alzheimer's disease, but we need to know whether the discoveries will 
actually work. Clinical trials are the only way to translate--and 
verify--the findings of basic research into real-world treatments.

    Senator Bond. Thank you very much, Mr. McConnell. I regret 
to tell you that you come before us at a time of very stretched 
budgets. Senator Mikulski and I are responsible for funding the 
veterans' health fund, EPA, National Science Foundation, and 
the initial numbers we have for those are definitely 
underfunded, and the National Science Foundation, which I 
believe supports some of the work at NIH.
    Mr. McConnell. That is why we are asking for a modest $40 
million increase.
    Senator Bond. Well, that is good. I appreciate that. Thank 
you for that. We would love to be able to fund this and the 
other things, but we do have a tight budget.
    Let me phrase a question just generally. We are very 
interested on the committee in seeing how we can get quality 
care for our Nation's elderly. If there is one thing that we 
can do immediately for the patients and the families who have 
family members with Alzheimer's--let us start with you, Dr. 
Hodes--is there one thing we can suggest to a family with a 
patient with Alzheimer's? What can we do?
    Dr. Hodes. I think most immediately, as you have heard from 
Dr. Morris and Dr. Rabins, we have an enormous commitment to 
educate, while emphasizing at the same time--and I should again 
repeat our gratitude to Congress for its support and for the 
enormously effective partnership that Alzheimer's research has 
had with the Association.
    In addition to our long-term goals of finding the ways and 
means to improve upon our ability to diagnose, treat, and 
prevent, our most proximal or immediate goal is that of 
educating and informing. We have to inform the public of the 
ability to accurately diagnose disease so it can be diagnosed, 
and we have to inform the public of the opportunities there are 
to treat, albeit they are still imperfect and temporary 
solutions which nonetheless do translate in a fraction of 
individuals to a longer time in touch with their families and 
loved ones, at home and out of institutional settings.
    So this is I think going to be a part of the mission, we 
appreciate, together with academic institutions and the 
Alzheimer's Association, informing the public about what is 
available. This is a constant balance we have, to be doing the 
research now so that 20 years from now, we will have better 
interventions, hopefully the definitive ones, but at the same 
time to translate what is now effective into practice by the 
largest possible community in this country and around the 
world.
    Senator Bond. OK. So the first thing would be if there is a 
question, get an accurate diagnosis, and then some immediate 
things can flow from that.
    Dr. Morris, would you like to respond?
    Dr. Morris. I would just augment Dr. Hodes' remarks to 
emphasize that early recognition can benefit both the patient 
and the family. Too often, families bring patients in for 
diagnosis when there is a crisis--someone living alone no 
longer is safe to live alone, someone driving gets into a car 
accident, problems with financial mismanagement--all sorts of 
difficulties that occur in the more moderate or advanced stages 
of the disease.
    Earlier recognition, when patients are still relatively 
functioning, can allow not only treatments to help maintain 
that relatively good functioning longer than would occur 
without the treatment, but it also allows the patient, family, 
and physician to begin planning for future years to avoid these 
crises, so driving cessation can occur before there is a crash; 
assisted living can occur or home health can occur before the 
individual living alone leaves on the stove burner, forgets to 
turn it off, starts a fire.
    So earlier recognition, earlier treatment, earlier planning 
to protect assets, to determine who should have durable power 
of attorney to be in charge of decisionmaking when the 
individual no longer can do that, I think would go a long way 
to alleviating some of the very difficult crises that patients 
and families go through if they wait to get the diagnosis and 
treatment.
    Senator Bond. Thank you.
    Dr. Rabins?
    Dr. Rabins. I would just build upon those remarks by 
mentioning that I included in my testimony a study that I have 
just completed in Maryland, actually, where we looked at a 
random sample of older people living in the State, and we found 
that of all the people with Alzheimer's disease, only one-third 
were known to their doctor to have any problem with memory. So 
that two-thirds of people with Alzheimer's disease are not even 
recognized by their doctor.
    So the treatments that we do have, the education, the 
medications, all these early important activities that Dr. 
Morris mentioned, cannot happen when the doctor has not even 
noted that there is a problem.
    So I think that if we could do one thing, as Dr. Morris 
said, it would be improving recognition by families and doctors 
that there is a problem, because then that gets people the help 
they need earlier.
    Senator Bond. Mr. McConnell?
    Mr. McConnell. There are simple caregiver supports that can 
make a huge difference. Respite care is the number one thing 
that people ask for. Most of the care is being provided by 
family members, and they do it 24, 36 hours a day, and some 
respite care, some simple counseling, can make a difference.
    There was a recent study that came out of NYU about some 
simple counseling procedures that appear to reduce depression 
among caregivers. We funded a study in Cleveland that provided 
some simple training for caregivers that not only helped them 
provide better care but significantly reduced emergency room 
use and unnecessary hospitalization. So there is a cost saving 
as well as a benefit to the caregivers.
    But the problem is that we have those supports, and 
certainly a tax credit and the Lifespan Respite Care Act can 
all be very helpful, but people are not getting diagnosed, they 
are not being told by physicians that there is an Alzheimer's 
Association that can provide them with information and support, 
and until we have the medical community better trained and 
better educated about what is possible, and more knowledgeable 
about this, people will not get access even to the services 
that are available now.
    Senator Bond. I guess one thing that people need to know is 
the telltale signs, and I gather that memory loss, forgetting 
recently learned information, difficulty performing familiar 
tasks like how to prepare a meal, using a household appliance, 
and participating in a hobby, problems with language, 
disorientation in time and place--these are the kinds of things 
that you look for first, and I assume--there were several 
references to materials--I gather those are in the materials 
that the Alzheimer's Association and Dr. Rabins and others have 
available?
    Mr. McConnell. We have something called ``The 10 Warning 
Signs'' that we have tried to publicize so the public can ask 
those questions, or more likely a family member recognizes some 
of those symptoms and gets a person to a physician to get a 
diagnosis.
    Senator Bond. Thank you.
    I will turn it over now to Senator Mikulski.
    Senator Mikulski. Thank you very much, Mr. Chairman.
    I am going to jump around a little bit. Mr. McConnell, how 
much did you say the Alzheimer's Association spends every year 
on research?
    Mr. McConnell. This year, we will fund about $17 million in 
research grants, and since our founding in 1980, we have 
committed $150 million to research.
    Senator Mikulski. That is really stunning when you think 
that this was done on Alzheimer's walks and all kinds of very 
grassroots fundraising. And really, you and all the members of 
the Association should be complimented on that.
    I am going to come back with some ideas on that, but Dr. 
Hodes, obviously, the doubling of the budget has had a great 
impact. When I embarked upon this topic 20 years ago, the 
progression in our family was all the 10 signs that you have 
indicated, Mr. McConnell, and others began to appear in 1982, 
and 1984 is when we turned to Dr. John Burton at Hopkins for 
geriatric evaluation and then went into a specialized day care 
program that provided 3 mornings a week for Dad; Mother could 
take a break, and Dad was in these memory stimulation and other 
groups. In 1986, we had to turn to long-term care, and in 1988, 
my father passed away.
    But every hearing I held was so gloomy and doomy and 
fatalistic and so on. This has so much energy. This has so much 
possibility--and also, it is comprehensive, from the family to 
basic themes like cholesterol and diabetes management that will 
have an impact to really enormously sophisticated drugs and 
genetic therapies.
    So it shows that truly, money could make a difference in 
this case.
    Is this right, Dr. Hodes? And Mr. McConnell has talked 
about $40 million, and Senator Bond is right about the $40 
million, but could you tell us what an increase in funding 
could lead to, or the amplification of a study?
    Dr. Hodes. To begin with, I can certainly point to how 
important the doubling just accomplished has been. It has been 
true at the level of the most stunning, as you characterized 
them, basic science studies which are really probing at 
molecular genetic levels the underpinnings of the disease. It 
is also quite evident in the list that I provided of some of 
the prevention and treatment trials that are ongoing the fact 
that we have now opened a number of potential targets which we 
can, with adequate funding, approach in parallel rather than in 
sequence is critically important.
    The nature of science, and particularly biological 
investigation, is that we do not know whether it is going to be 
the trial of statins or of ginkgo biloba or of anti-
inflammatories or of the other agents that we are testing, 
which will be the most effective. And our best opportunity to 
find an effective treatment or treatments before the crisis is 
upon us is to be able to pursue these multiple outstanding 
opportunities created by past and present basic science.
    As noted, the increase in budget has now leveled off, and 
we at NIA and all of NIH will continue, of course, to do our 
very best to fund the best science at best judgment with this 
limitation on funding. You have heard some of the numbers 
expressed, and I can certainly validate what they are.
    We have characteristically been able to fund approximately 
25 to 30 percent of the most outstanding grants over the past 
several years. This year, our estimate is that that number will 
be approximately 15 to 17 percent. And as was alluded to by 
Steve McConnell, in order to accomplish this, we have actually 
had to make reductions in those awards that we do make, the 
alternative being to fund even fewer.
    This is not a case where of course we are going to say the 
most promising studies will not happen. That would be 
irresponsible, and that is not what we would do. But we would 
not be able to carry out the number of studies at the pace 
which is optimal and could be driven by basic discovery.
    In that case, simply put, there is now an unprecedented 
richness of opportunities and proposals.
    Senator Mikulski. I got it. And I think what I would like 
to do--and I want to acknowledge what Senator Bond said; it is 
a tight time--but is to reach out to Senators Specter and 
Harkin to just say what $40 million would mean, because they 
have a lot of pondering to do--and we do not want to get into 
earmarking research, but the idea that this Institute in the 
scheme of doubling the NIH budget for really, in many ways, a 
modest increase, the possibilities here, because the 
consequences again to family and budget and other issues are so 
enormous. So we will come back to that.
    I want to go to, while we are looking for cures and the 
genetic underpinnings, all of which we want to continue to 
support, the ability for cognitive stretchout.
    Dr. Rabins, could you fill us in or summarize some of the 
promising ideas? I note that there is a drug called Memantine--
how do you say that----
    Dr. Rabins. Memantine.
    Senator Mikulski [continuing]. Memantine--and then also, 
this whole idea of chelation. What is going on--because the 
delay of onset would be really enormous.
    Dr. Rabins. I think what we know now is that these 
medicines that we have, at least the way I present it to 
families, can improve a person by approximately 6 to 9 months. 
About two-thirds of people have some response to these 
medicines, so the average person would get somewhat better, but 
that is a modest improvement.
    As far as we know, these medicines do not really slow down 
the progression of the disease. Some people think that they 
might, but that has not been demonstrated. So the medicines 
work, they work very modestly. But that does tell us that it is 
possible to change what is going on in the brain. I think if 
nothing else, what we have already tells us that we can change 
the disease, so we know we can do a lot better.
    Senator Mikulski. But, Doctor, what slows down? I will wait 
for a second round to go into chelation and this ginkgo biloba 
study and so on. But if we say there is modest improvement, but 
it does not slow down, what is the nature of the improvement?
    Dr. Rabins. Well, the improvements seem to be in the area 
of thinking, so all the thinking problems--and Senator Bond 
mentioned a number of them--memory, judgment, doing everyday 
activities--people show improvements in all of those areas, 
modestly. And second, people do become somewhat more 
functional, so they are a little bit more able to function in 
everyday life. They are a little better able to dress 
themselves, bathe themselves--and although these things do not 
sound so major, when you are a family care provider----
    Senator Mikulski. No--they are major.
    Dr. Rabins [continuing]. If someone can get dressed when 
they needed help before, that is a tremendous change.
    So it is both in the area of memory and thinking and in the 
area of everyday functioning that people improve.
    Senator Mikulski. Thank you.
    Senator Bond. Thank you very much, Senator Mikulski.
    I am going to ask unanimous consent that a statement by Mr. 
Eric Hall, CEO of the Alzheimer's Foundation of America, be 
included in the record as if read. Without objection, it will 
be.
    [The prepared statement of Mr. Hall follows:]
                    Prepared Statement Of Eric Hall

                 THE ALZHEIMER'S FOUNDATION OF AMERICA
    Chairman Bond, Ranking Member Mikulski, and distinguished 
Subcommittee Members, on behalf of the Alzheimer's Foundation of 
America (AFA), thank you for holding this important hearing on 
Alzheimer's disease and recent breakthroughs in medical research. Your 
leadership on these issues is vital to the success of ongoing work to 
find a cure for Alzheimer's disease.
    I appreciate the opportunity to provide information about AFA 
members' related efforts to meet the educational, social and emotional 
needs of individuals with Alzheimer's disease and their families and 
caregivers, while raising public awareness about the disease and 
lending expertise to healthcare professionals. I also want to highlight 
an important initiative launched by AFA to promote memory screening 
with the goal of early diagnosis of Alzheimer's disease and related 
dementias.

The Foundation's Mission

    The Alzheimer's Foundation of America (AFA) is a nonprofit 
501(c)(3) organization founded to fill a gap that existed on the 
national front for advocacy of ``care. . . in addition to cure'' for 
individuals affected by Alzheimer's disease and related dementias. Our 
goals include improving quality of life for all those affected and 
raising standards for quality of care.
    AFA operates a national resource and referral network with a toll-
free hotline, develops and replicates cutting-edge programs, hosts 
educational conferences and training for caregivers and professionals, 
provides grants to member organizations for hands-on support services 
in their local areas, and advocates for funding for social services. It 
annually sponsors two national initiatives, National Memory Screening 
Day and National Commemorative Candle Lighting.
    Founded in February 2002, AFA now represents organizations in 
nearly all 50 States. The majority of AFA members provide direct, 
hands-on educational and social services in their local communities 
that help individuals and their families cope with this devastating 
disease. AFA has also established collaborative partnerships with other 
national groups, including The Leeza Gibbons Memory Foundation, Project 
Lifesaver and Sunrise Senior Living.

The Importance of Memory Screening

    AFA launched National Memory Screening Day in 2003 as a 
collaborative effort by organizations and health care professionals 
across the country to promote awareness and early detection of memory 
impairments. AFA initiated this effort in direct response to 
breakthroughs in Alzheimer's research that shows the benefits of early 
medical treatment for individuals with Alzheimer's disease, as well as 
the benefits of counseling and other support services for their 
caregivers. AFA's National Memory Screening Day underscores the 
importance of early diagnosis, so that individuals can obtain proper 
medical treatment, social services and other resources related to their 
condition. With no cure currently available for Alzheimer's disease, it 
is essential to provide individuals with these types of interventions 
that can improve their quality of life while suffering with the 
disease.
    During National Memory Screening Day, healthcare professionals 
administer free memory screenings at hundreds of sites throughout the 
United States. A memory screening is used as an indicator of whether a 
person might benefit from more extensive testing to determine whether a 
memory and/or cognitive impairment may exist. While a memory screening 
is helpful in identifying people who can benefit from medical 
attention, it is not used to diagnose any illness and in no way 
replaces examination by a qualified physician.
    The benefits of an early diagnosis of a memory disorder are 
enormous. Early diagnosis can go a long way toward improving quality of 
life. National Memory Screening Day represents a giant step toward 
leading individuals up the right path.
    Our goal is for individuals to follow up with the next steps--
further medical testing and consultation with a physician, if the 
testing raises concerns. The latest research shows that several 
medications can slow the symptoms of Alzheimer's disease and that 
individuals begin to benefit most when they are taken in the early 
stages of memory disorder. This intervention may extend the time that 
patients can be cared for at home, thereby dramatically reducing the 
costs of institutional care.
    With early diagnosis, patients and their families can also take 
advantage of support services, such as those offered by AFA member 
organizations, which can lighten the burden of the disease. According 
to several research studies, such care and support can reduce caregiver 
depression and other health problems, and delay institutionalization of 
their loved one--again reducing the economic burden of this disease on 
society.
    In addition, with early diagnosis, individuals can participate in 
their care by letting family members and caregivers know their wishes. 
Thus, memory screenings are an important tool to empower people with 
knowledge and support. Just as importantly, the screenings should help 
allay fears of those who do not have a problem.
    AFA holds National Memory Screening Day on the 3rd Tuesday of 
November in recognition of National Alzheimer's Disease Month. AFA 
sponsors it in collaboration with The Leeza Gibbons Memory Foundation. 
Ms. Gibbons founded The Leeza Gibbons Memory Foundation in response to 
her own family's trial with Alzheimer's. She lost her grandmother to 
the disease, and her mother now battles with the final stages of 
Alzheimer's.
    This year, National Memory Screening Day will be held on November 
16, 2004. Individuals concerned about memory problems will be able to 
take advantage of free, confidential screenings at hundreds of sites 
across the country with the goal of early diagnosis of Alzheimer's 
disease or related dementias. Early diagnosis is critical, because as 
Ms. Gibbons has noted, ``This is not a disease that will wait for you 
to be ready.''

The Need for Federal Leadership

    As promising research continues in the search for a cure, 
additional resources are also needed in support of efforts to delay the 
progression of Alzheimer's disease and related dementias. The Federal 
Government can play a critical role in that regard by providing 
resources for a public health campaign designed to increase awareness 
of the importance of memory screening and to promote screening 
initiatives.
    Federal support is essential to expand the scope of ongoing efforts 
in the private sector. Working in partnership with AFA and other 
participating organizations, the Federal Government can leverage its 
resources cost-effectively to help overcome fear and misunderstanding 
about Alzheimer's disease and related dementias, to promote public 
awareness of the importance of memory screening, to expand options for 
screening nationwide, and to direct Americans to the support services 
and care available in their local communities.
    AFA appreciates the subcommittee's leadership on these issues and 
welcomes the opportunity to work together to improve the quality of 
life for Alzheimer's patients, their families and caregivers. (322 8th 
Ave., 6th Fl, New York, NY 10001, Tel 866-232-8484, Fax 646-638-1546). 
(www.alzfdn.org).

    Senator Bond. I would like to turn to Dr. Morris. We heard 
earlier about the imaging and the clinical trials. Can you give 
us an idea why imaging is so important in clinical trials?
    Dr. Morris. Yes, thank you.
    Let me begin by indicating now that the treatments that Dr. 
Rabins just discussed help people modestly. A reason for that 
is that we initiate treatments when we diagnose the disease. We 
diagnose the disease when dementia occurs--memory loss, other 
problems. By the time memory loss has occurred, we know already 
that there is substantial brain damage. In some vulnerable 
areas of the brain, already 60 percent of nerve cells have died 
by the time the diagnosis is made. In some sense, if we wait 
until dementia appears so that we can make the diagnosis, it is 
too late to have any major therapeutic effect. The brain is 
already substantively damaged. Hence, in order to optimize 
treatment, we have to recognize the illness at stages before 
that substantial brain damage occurs, when it is just beginning 
in the brain.
    Dr. Hodes mentioned this very exciting imaging study where 
we can now introduce a tracer into the bloodstream of a 
patient, it gets into the brain, and it attaches to the 
beginning brain changes of Alzheimer's disease at a stage 
before many nerve cells are lost.
    So the value of imaging is early detection, detection 
before the stage of dementia, and will give us an opportunity 
to evaluate interventions to fix that abnormal brain stage. So 
we can not only use imaging as a potential tool for 
presymptomatic recognition of the disease before substantial 
brain damage has occurred, but also monitor the effective 
treatments that attack the actual underpinnings of the 
disease--not the symptoms, but the causes that result in nerve 
cell death.
    What we are talking about is prevention of Alzheimer's 
disease.
    Senator Bond. Normally, what would you say are the 
symptoms, what are the indicators that would merit such an 
intervention? If you tell me that half of 85-year-olds have 
Alzheimer's disease, it would seem to me that 100 percent 
testing when you are going to get 50 percent hits would make 
sense. What would be either the age or the early indicators 
before the loss of brain cells occurs that would warrant 
widespread use of these tests?
    Dr. Morris. Well, that is an excellent point, because we 
cannot do a brain image in every 60-year-old or 50-year-old. It 
is just too expensive and too difficult. So we have to narrow 
it down to people who already seem to be at increased risk.
    One way that there is increased risk is we know that if 
there is a family member--a parent or a brother or a sister--
with the disease, the genetic inheritance puts individuals at 
greater risk.
    Hence, I think we need to look at these high-risk 
individuals to see if they are beginning to develop the 
illness, and when we get these new interventions that attack 
the disease process, that is the target group for the 
interventions, rather than to give it to everybody.
    Senator Bond. Would things like diabetes and high blood 
pressure be indicators as well, so that diabetics should be 
included, or is that too broad a category?
    Dr. Morris. Actually, I think there are many possible risk 
factors. Diabetes is one. But I would say that we can do even 
better than just broad risk factors. I think we can look at 
individuals who are specifically at risk for Alzheimer's 
disease.
    There is no question that anything that damages the heart--
high blood pressure, high cholesterol, diabetes--is bad for the 
brain. There is no question about that. But we are talking 
about specific causes of Alzheimer's disease, and we can look 
at the specific risk factors for that.
    Dr. Rabins. Could I add something to that, Senator?
    Senator Bond. Sure.
    Dr. Rabins. You are actually thinking like a scientist, and 
all the questions you are asking are the kinds of questions 
that a scientist would ask. And only with study will we know 
that there is a given age at which it is worth doing, or 
particular conditions. So it is those kinds of studies that 
will build upon this imaging initiative that will answer the 
kinds of important questions you are asking.
    Senator Bond. Dr. Hodes?
    Dr. Hodes. I think we all have the same thought, that we 
probably ought to recruit you to some of our study sections, 
because you are really asking precisely the correct questions.
    But as examples of some of the instances in which imaging 
abnormalities have been seen in populations at high risk and 
may begin to answer the question that you have posed, they 
include studies that have been done on individuals with genetic 
high risk of disease--either carrying the APOE allyl or even in 
early onset--and are quite striking, and it remains to be seen 
what the final implications will be of these studies. In 
individuals with APOE-4, a risk factor for increased likelihood 
of Alzheimer's disease, it has been shown that individuals in 
their middle years, and most recently in one report, even in 
their twenties and thirties, begin to show some of the brain 
changes in imaging that are characteristic of patients with 
Alzheimer's. This is a clue that some of the early changes may 
be detectable in a population that is at genetic high risk and 
begins to address the very important questions that you are 
asking--what are the populations that we should target for this 
kind of diagnostic intervention, and from a research point of 
view, which of the populations we should target for 
experimental treatments to prevent progression of disease.
    Senator Bond. Thank you.
    My apologies to my colleagues. Just one last question--and 
I might ask if Mr. McConnell has anything he wants to add on 
that.
    Mr. McConnell. There is a question right now about whether 
this PET scan technology which is getting a huge amount of 
attention should be covered by Medicare, and the general sense 
is that it is not ready in a general population for that 
purpose, but as a research tool, it is very important, and I 
think there is huge hope for imaging being both a diagnostic 
tool and to help move treatments more quickly to the market.
    But we do not support broad-scale screening, because you 
can create mass hysteria out there. A lot of us are worried 
about our memories, and I think it is important that we target 
those people right now who are showing some significant deficit 
and not try to scare the whole population by massive screening.
    Senator Bond. One final thought--you are telling us it is 
cardiovascular, it is blood-related, and you talked about 
elements in the brain. Do any of these show up--because almost 
all of us from time to time should be having blood tests to 
check our cholesterol that would indicate the need for imaging?
    Dr. Hodes. I think any of the experts here can address this 
question, but the short answer to your question is that there 
certainly are risk factors determined by blood tests which 
identify individuals at a higher risk. These include such 
things as high cholesterol or high homocysteine levels.
    What remains as an important link is to prove that 
treatment of those risk factors will actually affect the risk 
of disease, and those are studies ongoing. So if one affects 
cholesterol with drugs like statin, which has many effects, or 
with folic acid, which can reduce homocysteine, the clinical 
studies now in progress will help to identify whether these are 
risk factors which when modified will actually translate into a 
prevention or slowing of disease.
    Senator Bond. Thank you very much.
    We have been joined by the senior Senator from Connecticut.
    Senator Dodd, would you care to make a statement or ask 
some questions?

                   Opening Statement Of Senator Dodd

    Senator Dodd. Thank you, Mr. Chairman, and I apologize for 
arriving a few minutes late.
    Let me thank you and Senator Mikulski for holding this 
hearing. I think it is tremendously worthwhile. I represent a 
small State of 3.5 million people, and 470,000 of my 
constituents are older Americans, and 100,000 of those 470,000 
are at one stage or another of Alzheimer's disease. I think our 
State ranks ninth in the country because we have an older 
population.
    I also wonder whether there are environmental implications 
to all of this--you may have talked about this before I 
arrived--in addition to the lifestyle issues.
    As a layman--and I am talking to a panel of professionals--
but watching what appears to be--maybe it is because there is 
better detection available today--but what seems to be an 
increase in the number of diseases, I am wondering if there are 
more environmental implications than we are willing to admit or 
look at that are provoking some of this increase in a number of 
related areas, Alzheimer's being one of them. I wonder if you 
might talk about that.
    Second, you may have addressed this already, and I know 
this is a subject of some controversy, but I want to express my 
admiration for Nancy Reagan and her comments the other day 
before the Juvenile Diabetes dinner in Los Angeles. I spoke at 
the dinner for the Northeastern Conference. I am very involved, 
and I have a godchild with juvenile diabetes, and every year, I 
am very much involved in their efforts in Connecticut and 
western Massachusetts. Obviously, the stem cell issue is an 
emotional one for a lot of people, but clearly, when you start 
talking about juvenile diabetes and Alzheimer's and Parkinson's 
disease and others, being able to access, particularly as there 
is an effort now with the frozen embryos that may be discarded 
shortly, it would be a great pity in my view if we did not take 
advantage of that existence to utilize the efforts that are 
being made to try to come up with ways to effectively deal with 
Alzheimer's.
    So I would like to ask the panel if you have not already 
addressed these questions about, one, the environmental issues 
generally speaking--and I realize it is a broad question, and 
again, I realize the question is coming from a layman, but 
nonetheless I have the feeling and sense that more is going on 
here than we are really willing even to admit at this 
juncture--and second, I wonder if all four of you would comment 
on the embryonic stem cell issue.
    Dr. Rabins. I think as far as environment and the large 
increase in the number of people with Alzheimer's disease, as 
far as we can tell--and the research only goes back about 50 
years--the percentage of people who develop Alzheimer's disease 
at any given age is not increasing. What has changed is that 
for the first time in human history, it is common for people to 
live into their seventies and eighties. The average woman now 
in the United States lives to age 80. So if somewhere between 
20 and 35 percent of 80-year-olds have Alzheimer's disease, 
that is a huge number. Again, the average woman lives to 80, so 
that means the average woman has between a 20 and 35 percent 
chance of getting the disease.
    So the reason we are hearing so much about it is because of 
this change in the way the population is distributed. There are 
many more older people at risk.
    My own personal opinion about stem cells is that it is very 
difficult to predict whether they could be beneficial in 
Alzheimer's disease. We will obviously never know unless that 
kind of research goes on. I think the opportunity if they were 
to help would be very, very early in the disease--if we could 
find that there were a focus of cell death that triggered the 
disease and possibly reverse that. But it is a disease that 
ultimately envelopes almost the whole brain, so it is hard to 
see--although one never can tell--how stem cell research might 
influence the disease. That is my personal opinion.
    Senator Bond. Dr. Morris?
    Dr. Morris. I would just like to echo Peter's comments 
about the real influence of the aging of the society as the 
major driver for the increased recognition of Alzheimer's 
disease. I think by far and away, it is this demographic 
revolution that makes us have this epidemic before us.
    But it is interesting that all of those things that we have 
heard about, about keeping good health, good cardiovascular 
health, physical health, mental health--the things that Steve 
McConnell talked about--are really excellent. As a matter of 
fact, Steve talked about dancing, but it is known that staying 
mentally engaged is actually associated with some decreased 
risk of developing Alzheimer's disease, and one of the major 
factors I think is testifying before a Senate subcommittee; I 
think that is very protective.
    Senator Dodd. Hopefully those who are up here are 
remembering what you are saying to us.
    Dr. Morris. And I would just like to mention one thing 
about Nancy Reagan, not on the stem cell issue. I think too 
many people still have a stigma, a negative stigma, attached to 
Alzheimer's disease. It is one of the barriers for coming 
forward for early recognition. And I think President and Nancy 
Reagan's statement that he did have Alzheimer's disease several 
years ago was very courageous and went a long way toward 
reducing that stigma.
    Mr. McConnell. Senator, if I could pick up on that, I think 
one of the things that is happening is that people are being 
diagnosed earlier. So in addition to the longevity question, 
you have more people with the disease, more people are being 
diagnosed earlier, and we are finding that the conversations 
that happen at any meeting of the Alzheimer's Association have 
shifted, because there are present always people with the 
disease. They speak, they represent themselves, they feel 
strongly about these issues, and it has changed the 
conversation.
    I think it contributes to that sense that there is an 
epidemic, and it is an epidemic in the sense that it is growing 
in huge numbers and having huge impact. It just is not the same 
kind of epidemic.
    Senator Dodd. Do you want to comment on the stem cell 
issue?
    Mr. McConnell. We took a position against the Federal ban. 
We have tended to focus on other areas of promising research to 
lend our support, and as you have just heard, there are 
questions in the science community about this issue, but we 
felt that there should not be a Federal ban against stem cell 
research, because there may be some opportunities to explore 
understanding of how they work.
    Senator Dodd. Dr. Morris, did you want to comment on that 
as well, stem cells?
    Dr. Morris. I would have to say specifically for 
Alzheimer's disease that I think stem cell research is not 
likely to have an immediate impact. There are other neurologic 
diseases such as Parkinson's disease which affect a very 
discrete area of the brain for which the potential therapeutic 
impact of stem cell research I think will have much more 
immediacy than for Alzheimer's disease.
    So from a scientific standpoint, I think brain diseases, in 
particular those that affect only a local, discrete area of the 
brain, will potentially benefit more from stem cell research. 
Perhaps down the road, Alzheimer's disease may benefit also.
    Senator Dodd. Can I glean from that, then, that you would 
be opposed to a total ban on the stem cell research?
    Dr. Morris. Well, I have to tell you I am a scientist, so 
as a scientist, we like to be able to follow promising leads 
wherever they go.
    Senator Dodd. Thank you.
    Dr. Hodes?
    Dr. Hodes. In terms of the question of risk factors and 
environment, I would certainly reinforce what you have heard. 
Such issues as life style risk factors are part of environment. 
But Senator Dodd, you make an important point I think all of us 
would agree upon. We have to have appropriate humility about 
what we know and what we do not know, and I would stress that 
we are constantly looking in studies of the epidemiology and 
risk factors for any possible environmental or other factors 
which may play a role which we do not yet appreciate. I think 
we would all reinforce that most strongly.
    Senator Dodd. And on the stem cell issue?
    Dr. Hodes. In terms of stem cells, again I would emphasize 
that there is a broad spectrum of stem cell research that is 
being carried out in brain research, in Alzheimer's research in 
particular. It includes embryonic stem cells, adult stem cells, 
the demonstrated ability of cells within the brain itself to be 
potentially mobilized with differentiation.
    Clearly, our responsibility at the National Institutes of 
Health is to support all of that research which is consistent 
with policy set by the Federal Government.
    Senator Dodd. Thank you all very much.
    Mr. Chairman, thank you. I would note just in closing that 
years ago, when I first got involved, it was because of Yasmine 
Kahn's mother who had begun to talk about it. And in fact, Sil 
Conte, one of the early Members of Congress in the House really 
got involved in this issue.
    So we have come a long way, and I thank you very much.
    Thank you, Mr. Chairman.
    Senator Bond. Thank you very much, Senator Dodd.
    Senator Mikulski?
    Senator Mikulski. Thank you, Mr. Chairman.
    While we are talking about breakthroughs, I am going to 
return to the conversation of the more ordinary that came up. 
What I found so interesting were the issues about Motrin and 
Advil, issues of possible vitamin intervention, all of which is 
good health, the role that diabetes and cardiovascular is 
playing and the telltale signs.
    So, Dr. Rabins, in your newsletter, the Hopkins newsletter, 
you talk about the concept of metal chelation. I believe in the 
Archives of Neurology, you reported that there was a drug that 
worked on the chelation idea. Could you elaborate on that? We 
know that in lead paint poisoning, chelation really helped 
restore the cognitive ability of children, and you know that 
our City of Baltimore is one of the lead paint areas. Could you 
tell us what that means, and does this offer some promise to 
this, and is this something that should be explored more 
readily?
    Dr. Rabins. I think it is certainly something that should 
be explored. As we study the biology of these proteins that are 
being deposited in the brains of people with Alzheimer's 
disease, we are discovering all kinds of unsuspected things, 
and one of those is the fact that within these clumps of 
protein, there are these metal ions that are part of the 
deposition of these proteins. So, theoretically, it might be 
possible if one could remove some of those metallic ions that 
one might actually be able to remove some of the proteins that 
are being deposited.
    I think this preliminary study is very preliminary, and 
whether we can really change the course of the illness I think 
has not yet been demonstrated. But it is one of so many leads 
that we really need to study in a proper way.
    Senator Mikulski. And it is really a technique that has now 
been around for a while because of the issues like in lead 
paint; am I correct?
    Dr. Rabins. That is true. One needs to find particular 
medications for each different ion, so the question would be 
specifically what is happening in Alzheimer's disease, and are 
there drugs that can remove these ions, and then, does that 
really make a difference regarding disease progression. So it 
is an open question.
    Senator Mikulski. Dr. Hodes, and then I want to go to the 
vitamin approach and hear from the Center on Complementary 
Medicine about their ginkgo research.
    Dr. Hodes. Senator Mikulski, I was precisely going to 
suggest that the area of chelation, in addition to the topics 
you mentioned, Dr. Straus can speak to clinical studies that 
are currently ongoing.
    Senator Mikulski. Dr. Straus, maybe you could come up.
    Gentlemen, colleagues, this is Dr. Peter Straus, who is at 
the National Center for Complementary Medicine at NIH. Senator 
Harkin has been the prime mover in establishing this Center, 
and I supported him for two reasons. One, we wanted to be sure 
that as the whole information of complementary medicine 
exploded, the American people were prevented from quackery, to 
make sure they were not just on a fool's journey or even being 
victimized, and at the same time, lessons learned from other 
countries, particularly England, which uses complementary 
medicine, from acupuncture to botanical remedies and so on.
    Dr. Straus, it is good to see you. We have heard a lot 
about this ginkgo research, and you talked about stigma. There 
is a lot to joke about it, but you know, this is where our 
public is. You can pick up any vitamin book, and it says take 
this, and you do not have to take that; or this is going to 
lower your blood pressure and revitalize your relationship with 
your spouse, and all that.
    So people are doing it. The question is how can we ensure 
that we prevent them from going on a fool's journey and at the 
same time maybe embark upon a journey that is a breakthrough?
    Senator Bond. Before you start, I would say I hope it is 
not a total dead end, because I planted ginkgo trees along with 
my nut trees in Missouri.
    Dr. Straus. Mr. Chairman, Senator Mikulski, Senator Dodd, 
it is a pleasure to join my distinguished colleagues. As part 
of the NIH doubling, our Center was created at the NIH, and our 
purpose is to really help inform the public and practitioners 
about things that we may choose to do today, wise or not, while 
waiting for the genetic and diagnostic and biological and 
therapeutic interventions to come from our research 
laboratories.
    About half of my budget goes to aging-related research, 
because over one-quarter of Americans over age 60 are moving to 
use dietary supplements and various manipulative and exercise 
approaches and meditative approaches. These are hugely 
important.
    We are supporting in partnership with the Aging Institute a 
number of studies of antioxidant vitamins, micronutrients, the 
vitamin E and selenium study and the like. But I take 
particular pride in the studies that we have been doing with 
ginkgo biloba.
    As Dr. Hodes mentioned in his testimony, this is the 
largest study ever done of herbal medicine. There are 3,073 
patients, otherwise healthy Americans, age 75 and up, who have 
volunteered for a multicenter trial around the country. And we 
are asking whether the kinds of preliminary observations that 
emerged from Europe with ginkgo biloba were correct, whether it 
can prevent cognitive decline.
    To do a study like this and to do it right, to do justice 
to the over 3,000 volunteers for this study, requires all of 
the imaging and neurocognitive testing tools that we can bring 
to bear to diagnose the disorder, and that is what we are 
doing.
    We had believed initially that this study could be done 
with 2,000 patients. We had to enlarge it, and we will have to 
extend the study because the rate of----
    Senator Mikulski. Dr. Straus, where are you in this study? 
Are you just starting it, and what do you know about it 
already?
    Dr. Straus [continuing]. Senator, what we know is the 
following. This study is fully enrolled for the past year and a 
half. The rate of Alzheimer's events is less than we had 
predicted. We will have to extend this study longer to get its 
endpoint.
    But what we do know is that safety is always a concern with 
these agents, and we are tracking the patients carefully, and 
thus far there are no safety concerns whatsoever.
    Senator Mikulski. And what about the issues that others 
have talked about related to the antioxidants--you used those 
technical terms, but we know them out in the neighborhoods and 
communities as B12 and so on, vitamin E--because again, and I 
want my colleagues to know, we are using the standard Western 
medicine clinical methodologies--but Dr. Hodes, and maybe you 
want to elaborate on this, because these again go to the 
lifestyle issues that Mr. McConnell was talking about, and all 
of this in terms of things that can be used.
    Dr. Hodes. The general statement I think it is important to 
make is that we have a real responsibility in trying to weigh 
the potential gain versus potential risk of any intervention--
and interventions include such things as vitamins, so we do 
need to take great care.
    We have identified, as mentioned previously, risk factors 
such as, one example, homocysteine, that can be elevated as a 
risk factor and can be reduced by folic acid. Although there 
has been no proof, I should stress, that that will decrease the 
risk of Alzheimer's disease, the question is whether folic acid 
can be taken safely so there is little reason not to do it, or 
whether we need to be more careful of that.
    I think in the case of folic acid, in particular with 
dietary supplements, the decision has been made. Individuals 
are being exposed to folic acid. The folic acid content in a 
multivitamin has been so widely used there is little chance of 
it having an adverse effect.
    But I should point to examples where we have been sadly 
surprised in the past, such as high doses of antioxidant 
vitamins to prevent lung cancer in a study reported a number of 
years ago in a population of smokers. That study was stopped 
because there was, to everyone's surprise, an increase in the 
risk of lung cancer in individuals taking those vitamins.
    So I want to stress that the reason for carrying out 
careful studies, even if things that are called dietary 
supplements, can be critical both to identify what is effective 
but also to prevent terrible and tragic mistakes by taking 
treatments on the notion they could cause no harm when in fact 
the potential for harm is there.
    Therefore, as we have pointed out, for vitamin B, folic 
acid, vitamin E, these are all part of past and present 
rigorous clinical studies in which we will have the answers but 
do not yet, and until that time, I think we cannot in 
conscience make an evidence science-based recommendation about 
widespread use of materials that have not yet been shown to be 
without toxicity.
    Senator Mikulski. I see my time is up. I want to come back 
to Dr. Rabins' newsletter again, ``Health After 50.'' One thing 
it also talked about, while it talked about promising work in 
Alzheimer's, it says, ``Your dietary arsenal against eight 
serious disorders,'' and these are essentially tips for anyone 
who is looking for nutrition, exercise, etc. It goes through 
the kinds of programs you should follow if you have a 
propensity to diabetes and so on. After it goes through all 
that, it then says ``Action Steps,'' and it says to rely mostly 
on diet, that the best place to get vitamins is not out of a 
pill bottle but from a produce store. Then you go into ``Color 
Counts''--get enough vitamins C and E, and so on. I felt like 
Wonder Woman just reading it.
    But this takes me to another issue which is really the 
subject of another hearing, and that is that most doctors do 
not know about nutrition. There is so much confusing nutrition 
advice just as there is confusing vitamin research, gentlemen. 
There is so much confusion--should you be on ``sugarbusters''? 
Should you be on low-carb? Should you be on low-fat? Should 
you, should you, should you? America is really confused, and as 
a result, we are pursuing one fad after another--and maybe some 
of it has validity. We do not know that.
    What we also find, though, is that most physicians really 
do not offer advice. You get a little piece of paper that says 
why don't you follow this and so on. That is not a criticism of 
them. They are under tremendous stress. But I think we are 
going to have to also look at what goes on in clinical practice 
with very practical things in addition to very important drugs 
and surgical interventions.
    So I am not opposed to it, but everything that you have 
said here is that one of the best ways to begin to deal with 
this in yourself--you might not be able to beat genes, but you 
can delay the onset. And if you are managing your life in terms 
of other propensities you might have, you are also managing 
this.
    I think this is a subject of another whole hearing and 
discussion, but I want my friends at Hopkins to know that I 
really do read the newsletter.
    Dr. Rabins. Thank you, Senator.
    Senator Mikulski. I want to thank everybody, though, for 
all the work that you are doing, and we are so pleased that the 
complementary medicine is now integrated into sound research.
    Thank you, Dr. Straus. We could talk all day about this, 
but thank you.
    Senator Bond. Thank you, Senator Mikulski.
    I guess I will just get on your mailing list for the 
newsletter.
    Dr. Rabins. I will make sure you are, Senator Bond.
    Senator Bond. Thank you.
    I am on the Atkins diet, and it has kept the weight off me 
for a year and a half, so I hope the studies do not show it was 
a mistake.
    Let me come back generally to the subject at hand. Dr. 
Hodes, you mentioned the National Institute on Aging's REACH 
Project, that nine different social and behavioral 
interventions were tested for enhancing family caregiving. What 
were some of the more effective ones, and which interventions 
would you be including and combining in the second phase of 
your study?
    Dr. Hodes. The first stage was really a pilot that tested 
multiple interventions and multiple combinations in relatively 
small numbers, and I think the most rigorous answer is that 
none of the interventions actually achieved individually 
sufficient significance to be making recommendations on that 
basis.
    What this pilot study did, which is often the case with 
preliminary studies, is to suggest what might be most promising 
and combine them in a second stage, which is the study now in 
progress, that has more power in terms of numbers and specific 
protocols to provide an answer. We are about 2 years into that 
study, and my expectation is it will be 2 to 3 years more 
before we have the final answer that could potentially be 
translated into actual clinical recommendations.
    Senator Bond. Can you give us an idea of some of the things 
that are in this second-phase study?
    Dr. Hodes. They include such things are providing respite 
care, using World Wide Web and electronic access, networking--
multiple approaches that are designed to ease the burden and 
make it easier for caregivers to maintain loved ones in a 
noninstitutional setting.
    Senator Bond. I have been a long-time advocate of respite 
care for family members who are caregivers for adults with any 
kind of problem requiring assistance. I think that and in-home 
health care are extremely important and too often shortchanged 
in Medicare reimbursement. A few years ago, the unwise 
overreaching cuts in Medicare reimbursement for in-home health 
care shut down one-third of the home health agencies in my 
State, particularly in the rural areas, with devastating 
impact. That kind of care is so critically important, and we 
will continue to fight and to work on it.
    Mr. McConnell, just for the record, you might give us just 
a few of your ideas on the challenges faced by Alzheimer's 
caregivers, and what are some of the key factors that you see 
making caregiving for an AD patient so difficult?
    Mr. McConnell. If we break this up into people providing 
care in the community, the family caregivers and so forth, it 
is the constant stress. This is a disease where you have to 
keep track of somebody, and as Senator Mikulski knows, it is 
enormously stressful for caregivers and families. Many of these 
caregivers are themselves elderly, so they have their own 
conditions that they are dealing with; in many cases, they are 
frail and have their own health problems. The pressure of being 
a caregiver simply adds to those.
    And as you point out, by looking at just the long-term care 
side of this, we miss the fact that these are people who are 
using the health care system, and they are using Medicare, and 
the Medicare system is not set up to deal with people with 
chronic conditions, with Alzheimer's disease.
    Our research shows that Medicare spends three times as much 
if Alzheimer's is present with other chronic conditions, 
because Alzheimer's complicates the care; it is much more 
difficult to care for somebody.
    So those are the challenges. We have to make the health 
care system work better. We have to provide support for 
families. But I do want to mention that there are people, 
mostly in the later stages of the disease, who end up in an 
institution. And we talk about that nobody wants to be in a 
nursing home and so forth, but the fact of the matter is people 
need that kind of care when the family can no longer provide 
it, and many families keep caring for people too long. And we 
need to be sure that there is good quality care in those 
settings as well, and we have actually learned a fair amount 
about how to do that; we just need to get it implemented.
    Senator Bond. It seems to me that whenever I am home, the 
newspaper or the radio will report a tragic circumstance where 
an elderly person has disappeared, and sometimes it is from a 
good institution or an institution that thinks it is able to 
handle the patients, and they have just enough ability to slip 
out, or the tragic one is where the family is trying to give 
care, and it may be the middle of winter, and the AD patient 
goes out for a walk and never comes back.
    Mr. McConnell. The Alzheimer's Association has a Safe 
Return Program. It is a bracelet registry, so that if somebody 
wanders, the family can call an 800 number in Chicago, and 
immediately, emergency personnel are notified so they can look 
for this person. Police departments love this program because 
they struggle with these issues. If they find somebody with 
dementia, they do not know how to return them, or it costs a 
lot of money. If they have a bracelet, they can call an 800 
number when they find the person and return them home safely. 
It has been a very effective program.
    We are now looking at some of the new technologies, GPS and 
cell phone technology, that may be able to track people so that 
when they wander, you can find out right where that person is 
at any given time and retrieve them. This could be helpful.
    Senator Bond. You hate to think of using a GPS locator, 
normally a great invasion, but that might be the life saver for 
an Alzheimer's patient if that bracelet had a GPS chip that 
could be activated or was active. That is an interesting idea.
    I turn it back to Senator Mikulski.
    Dr. Rabins. Senator, if I may, could I add one thing?
    Senator Bond. Please.
    Dr. Rabins. It is about stress on caregiving. One thing 
that I think is often not appreciated is that about 60 percent 
of Alzheimer's patients have what has traditionally been called 
a psychiatric or behavioral symptom, and I think, as has 
already been mentioned, the greatest predictor of ending up in 
a nursing home is having Alzheimer's disease.
    If you have Alzheimer's disease, in fact, the greatest 
single predictor of going into a nursing home is having a 
behavioral symptom. So not only are there the physical burdens 
of caring for a very ill person, but many of these individuals 
have delusions, they think things to be true that are not true 
so they make accusations; they are fearful, afraid they may be 
poisoned; they hear things or see things that are not there; or 
they become depressed, and that further makes the disease 
worse.
    What is important about that is that in fact those symptoms 
often can be treated even when the disease itself cannot be 
changed. So one of the things that we have to help caregivers 
understand is that there are certain target symptoms that 
sometimes we can make a difference with, and hopefully, that 
will then improve the caregiver's quality of life.
    Senator Bond. Thank you very much.
    Senator Mikulski?
    Senator Mikulski. I think those comments were very 
insightful. From what we hear in the community, when the person 
with Alzheimer's begins to learn the ability to tell night from 
day, the so-called time reversal--waking up at 3 in the morning 
thinking it is 3 in the afternoon and wanting to live that 
way--the caregiver just starts to wear out, and then the 
children of the caregiver and the Alzheimer's family just get 
so frustrated and then move on to long-term care.
    This is where there is no real reimbursement for 
specialized day care--and I am not talking about babysitting 
here, I am talking about the kind that really offers ``maintain 
your brain'' activity, supervises medications for other 
situations, but also provides a breather.
    So I think we need to look at care in a continuum from 
prevention to early diagnosis to intermediate care--not only 
assisted living, but essentially assistance with living--and 
that is what some of these do.
    Mr. McConnell, can we come back to this idea of the 
Maintain Your Brain Campaign, which is really a robust 
grassroots effort, and could you tell us what that is composed 
of and essentially where did you get your ideas? Was it from 
the other research and so on?
    Mr. McConnell. Yes. There are a couple of things. I 
mentioned this brochure, and we are trying to get the word out, 
and it really comes from the scientists. We are very closely 
tied to the science community--we do not do things unless there 
is enough scientific evidence to support it--and we feel that 
there is. So there is a message that we can put out there, but 
getting the message out is part of the challenge.
    We created something called the Coalition of Hope. It is 
150 organizations now, from The Grange to minority groups; The 
Urban League is a part of this. It represents 50 million 
people, and these organizations are kind of the ``unusual 
suspects,'' we call them--they are not the ones that you 
ordinarily expect are going to care about this--but they are 
finding in their membership that they are confronting 
Alzheimer's disease--either their members have it or parents of 
their members have it--so they signed onto this Coalition of 
Hope to try to help us bring an end to this disease and make 
sure that there is support out there.
    Senator Mikulski. What are some of the tips that you give 
people?
    Mr. McConnell. The tips, as I mentioned, are to watch your 
numbers, to manage your cholesterol and your weight and so 
forth. There are vitamins that we think are useful to be sure 
your diet is good, and exercise.
    But some of it is to increase awareness. For example, in a 
week or so, we are going to release a report on the impact of 
Alzheimer's disease in the Hispanic community. There is not a 
lot of awareness out there in that community. We have not done 
a good job of reaching out. So we have to create awareness. 
Once there is some awareness, then people can be receptive to 
the messages about what they can do, and that is what our 
efforts are in Maintain Your Brain. Maintain Your Brain is a 
different message than has gone out there before. As you point 
out, this is a hopeful message. This is not depressing. There 
are actually things that can be done, and we think it will open 
people's minds up to dealing with this issue, whereas in the 
past, the curtain just came down when they heard ``Alzheimer's 
disease.''
    Senator Mikulski. What I find so interesting here is that 
when you go to page 2, it does talk about follow the numbers, 
feed your brain, etc, but there is also the issue that in 
certain ethnic groups, there seems to be a propensity toward 
certain risk factors. African American men are well-known for 
high blood pressure. There is the so-called barbershop 
outreach, where you get a haircut, and your blood pressure is 
taken, and we know in our own community that lives have 
actually been saved that way. Among Native American women and, 
again, African American women and Latino women, there seems to 
be a propensity toward Type 2 diabetes. This is a big deal 
because of consequences generally to health care and so on.
    Are you really focusing, then, through these practical 
things--because when you go around to the churches and 
community groups, you do not hear this kind of talk. You hear 
about access to health care--you hear about that a lot--and of 
course, access to jobs. Those are the two things that I hear. 
But then, there are the consequences. So how are you linking up 
to these communities?
    Mr. McConnell. As I said, the Coalition of Hope is a good 
start, because there are a number of organizations that have 
signed up for that that are saying exactly what you said, that 
we recognize these larger health problems, but the issue of 
Alzheimer's disease is something that we have not focused on.
    So we are trying to get information out, summarize the 
research on this, make sure there is better research showing 
the differences among ethnic groups. But it is a challenge. I 
think, exactly as you said, we need to go out through churches, 
through community groups--we need to stand at the WalMarts and 
get this message out there, which is what we are doing through 
our chapter network, to increase awareness, let people know 
there is something they can do and to engage them in dealing 
with this issue.
    Senator Mikulski. Well, this has been a wonderful hearing, 
Senator Bond. Thank you for providing the leadership for us to 
organize it.
    Each and everyone of you just offered such excellent ideas 
and hope, and it shows very clearly that our responsibility is 
to create the framework so these ideas can be explored.
    We could spend all day with each and every one of you, but 
you have your research and clinical practice to do, so we want 
to thank you. We particularly also want to thank the 
Alzheimer's Association. What a great, strong grassroots 
organization, and they just will not give up, and we are going 
to find those breakthroughs.
    So I want to thank you all for appearing today. You have 
given us a lot of things that we need to ponder and also some 
fiscal directions that we need to be looking at.
    Thank you.
    Senator Bond. Thank you, Senator Mikulski.
    It will challenge our minds to grasp the significance and 
the breadth of this problem. I had known about Alzheimer's 
anecdotally and through special areas where we have had 
problems, as I have mentioned, with providing the right kind of 
care in my State. But when you tell me that 85-year-olds have a 
50 percent chance of having Alzheimer's, that is something that 
we have to take seriously, and yet I think you have shown us 
that there are some promising avenues for us to pursue, and 
Senator Mikulski and I do not directly control it, but I think 
you can count on us being very strong supporters of the--what 
was it--you have squeezed it down to, what, $43 million?
    Mr. McConnell. Just a mere $40 million.
    Senator Bond. Just a mere $40 million, okay.
    Mr. McConnell. That is chump change up here, really, and it 
could do a huge amount.
    Senator Bond. Well, I know. Unfortunately, it is clear that 
there is some tremendous potential ahead, and we will not treat 
it as chump change. We will treat it and hope that our 
colleagues on the Labor-HHS Appropriations Subcommittee can 
find it.
    I really congratulate you, all the people with whom you 
work, and the organizations you represent, for your significant 
contributions.
    Dr. Straus, thank you very much for being here. I will have 
to check on some of the alternative medicines that I am taking 
after the hearing is over.
    With that, the hearing is adjourned.
    Thank you.
    [Additional material follows.]

                          ADDITIONAL MATERIAL

                      Academy Of Molecular Imaging
    Chairman Bond, Senator Mikulski and Members of the Subcommittee, I 
appreciate the opportunity to submit testimony on recent breakthroughs 
in Alzheimer's disease research and the importance of developments in 
molecular imaging for the early and accurate diagnosis and evaluation 
of Alzheimer's disease (AD) and related dementias. On behalf of the 
Academy of Molecular Imaging and of professionals involved in clinical 
care and research devoted to the welfare of patients with Alzheimer's 
disease and related dementias, we deeply appreciate the subcommittee's 
interest and scrutiny of the changes in scientific and clinical 
practice which promise to improve the outcomes and the quality of care 
for Alzheimer's and patients with other forms of dementia.
    As a health professional, it has been extremely exciting for me to 
observe and participate in the recent progress made in developing PET 
scans as a diagnostic and evaluative tool for these important diseases 
and disorders. Dementia is the most common cause of mental impairment 
in older persons, affecting 8 percent of those age 65 years and older 
and up to 47 percent of those in the age group 85 and above.
    Alzheimer's disease is the most common cause of late-life dementia, 
accounting for nearly 70 percent of cases. Other relatively common 
causes include vascular dementia, frontotemporal dementia, dementia 
with Lewy bodies, and depression.

Importance of PET Scans for Dementia

    PET scans, using 2-deoxy-2-[F-18] fluoro-D-glucose (FDG), provide 
measures of glucose metabolism that allow clinicians to make an early 
diagnosis of AD and other neurodegenerative disorders, predicting 
clinical progression and the autopsy diagnosis with superior 
sensitivity and accuracy, especially in the earliest stages of dementia 
when clinical impressions are least certain. PET determinations of 
glucose metabolism in AD show a specific pattern of decreased glucose 
metabolism beginning in certain regions and later spreading as the 
disease progresses. The extent of this hypometabolism correlates with 
the severity of cognitive impairment.
    A clinical evaluation that incorporates the use of FDG-PET is more 
accurate than clinical examination alone for the differential diagnosis 
and identification of various dementia causes. The improved diagnostic 
accuracy of PET early in the course of a dementia illness leads to more 
effective disease management. These conclusions are supported by 
studies showing greater diagnostic accuracy of FDG-PET using 
neuropathological confirmation of dementia type as the criterion 
standard of diagnostic accuracy and high predictive value of PET in 
studies including longitudinal clinical follow-up. Furthermore, the 
approval by the United States Food and Drug Administration (FDA) of 
several drugs proven efficacious for the treatment of early, mild 
Alzheimer's disease brings new urgency to the need for reliable 
differential diagnostic methods in patients with early symptoms of 
dementia.
    It is also the case that at the stage of mild dementia symptoms in 
the elderly, about 50 percent of these patients do not have Alzheimer's 
disease. The addition of PET to the clinical work up provides the most 
accurate means to separate those who have early Alzheimer's from those 
who do not. Both outcomes are important for the patient and their 
family to know.
    Finally, the safety of FDG is well established through studies by 
the FDA, under New Drug Application (NDA) #20-306, and the peer-
reviewed literature, representing approximately 2 decades of clinical 
use of the radiopharmaceutical. No significant adverse reactions 
attributable to FDG were identified by the FDA or in the general 
scientific literature involving the use of FDG, nor in a recent article 
reporting the results of a 5-year prospective study on radiotracers 
used in nuclear medicine at 18 collaborating institutions. Further, 
under the approved NDA, FDG has been shown to be safe and effective in 
brain imaging in patients with epilepsy, another condition in which 
hypometabolism may exist in specific areas of the brain associated with 
elliptogenic tissue in the absence of seizures, and there are no new 
factors introduced in this request to alter the safety profile of FDG.

Importance of Early Diagnosis

    The need for early and accurate diagnosis has become more urgent, 
now that several prescription medications for the treatment of mild to 
moderate AD are available, as patients with neurodegenerative disease 
have the most to gain from effective therapies that intervene as early 
as possible in the course of inexorably progressive irreversible damage 
to brain tissue. Controlled clinical trials have demonstrated that 
cholinesterase inhibitors can improve, or delay decline in, memory and 
other cognitive functions in AD patients. These treatments can cut by 
more than half the proportion of patients requiring nursing home 
placement over a given period of time.
    Those studies that have examined long-term effects of 
cholinesterase inhibitors indicate that drug treatment produces an 
average delay in cognitive decline in AD patients of 9 to 12 months, 
relative to the time-course of untreated patients, and a delay in the 
need for institutionalization of 18 months, which may represent a 
substantial portion of the patients' remaining life expectancy. 
Moreover, delaying the institution of therapy by as little as 6 
months--in addition to carrying the inherent adverse consequence of 
depriving the patient of the short-term advantages of potentially 
enhanced mental activity and diminished cognitive decline during that 
time--may have long-term disadvantages as well.
    Early detection and differentiation of AD offers several additional 
benefits. For example, many people wish to know about a poor prognosis 
while their memory losses are relatively mild, in order to better plan 
for their future. This knowledge allows physicians, patients and family 
members the opportunity to address safety issues, as well as to 
identify surrogate decision-makers and sources of caregiver support, 
early in the disease process when patients can participate in these 
decisions. Furthermore, such benefits have been shown to reduce the 
need for nursing home placement of patients with mild dementia by 82 
percent, to delay nursing home placement of all AD patients by an 
average of 11 months, and to generally enhance quality of life for 
patients and their families. Finally, early accurate diagnostic 
approaches may also help to avoid the costs, efforts, and frustrations 
associated with years of multiple diagnostic evaluations. As summarized 
by the U.S. Agency for Health Care Policy and Research, ``early 
recognition of the condition has important benefits,'' and yet, 
``early-stage dementia is often unrecognized or misdiagnosed.''

Accuracy of Conventional Work-up for Dementia in Patients With Early 
                    Symptoms of Cognitive Decline

    How accurate is the conventional diagnostic work-up in the context 
of evaluating early dementia? This is a difficult question to answer, 
for at least two reasons. First, clinical definitions of when dementia 
begins are necessarily arbitrary, as a long period of gradual 
neuropathologic changes in the brain typically precedes the appearance 
of cognitive symptoms by years before there are significant enough to 
clearly fall below the normal range, making disease onset quite 
insidious. Biochemical changes occur over many years and are more 
severe than one would perceive from assessments of cognitive decline 
due to compensatory responses in the brain that act to maintain normal 
cerebral function in the face of progressive degeneration.
    Second, remarkably few studies specifically addressed the question 
of clinical detection of very mild disease, particularly with 
comparison to the criterion standard of histopathologic diagnosis. In 
one investigation aimed at doing so, patients who initially appeared 
normal or minimally affected were followed with repeated examinations 
for an average of 4 years. Even by the end of this longitudinal follow-
up period of many repetitious examinations, a neurologist examiner 
detected AD in only 70 percent of the patients who were histologically 
positive.
    In the recent report of the Quality Standards Subcommittee of the 
American Academy of Neurology, the source of the most comprehensive 
guidelines and standards for the clinical evaluation of dementia in the 
last several years, three ``Class I'' studies were identified in which 
the diagnostic value of clinical assessment could be meaningfully 
measured. Class I indicates ``a well designed prospective study in a 
broad spectrum of persons with the suspected condition, using a ``gold 
standard'' for case definition, and enabling the assessment of 
appropriate tests of diagnostic accuracy.'' Only one of them focused 
upon evaluating dementia at a relatively early stage. To be included in 
that investigation, patients were required to have had onset of 
dementia symptoms within 1 year of entry. All of the 134 patients 
evaluated underwent a complete standardized diagnostic work-up 
comprised of a comprehensive medical history and physical, neurological 
examination, neuropsychologic testing, laboratory tests, and structural 
neuroimaging, and an average of 3 additional years of clinical follow-
up with repeated testing. Sensitivity of this assessment for AD was 83-
85 percent, while specificity was 50-55 percent. It should be 
emphasized that in the studies described above, and in most similar 
studies, the reported sensitivities and specificities represent not the 
diagnostic accuracy of initial clinical evaluation, but one that is 
reached at the end of an entire series of evaluations repeated over a 
period of years and at a time when AD patients have advanced to more 
severe stages of disease than when testing was initiated. It should 
also be emphasized that the accuracy reported with PET is for a single 
PET scan taken at the stage where the patient has mild disease.
    When neuroimaging is obtained in the evaluation of dementia, 
patients are usually referred for a structural imaging examination--
i.e., MRI or CT of the brain. Conventional MRI or CT of patients with 
symptoms of dementia may be useful for identifying unsuspected 
clinically significant lesions (e.g., strokes and tumors), present in 
approximately 5 percent of patients. However, in patients with AD 
(which is much more common), such scans are typically read as normal, 
or as demonstrating the nonspecific finding of cortical atrophy or, 
worse still, as revealing ischemic changes that are (mis) interpreted 
as pointing to cerebrovascular disease as the primary or sole process 
responsible for the patient's cognitive decline--in turn, leading to 
failure to institute appropriate pharmacotherapy (e.g., donepezil, 
rivastigmine, galantamine, all of which are FDA-approved only for the 
indication of ``mild to moderate dementia of the Alzheimer's type.'').
    It is unfortunately not rare for that type of misinterpretation to 
occur, even among expert clinicians. In a multicenter study involving 
seven university-affiliated Alzheimer's Disease Diagnostic and 
Treatment Centers, among patients diagnosed after clinical and 
structural neuroimaging evaluations as having ``vascular dementia,'' 
and in whom other dementia diagnoses were specifically thought to be 
absent, less than 30 percent of those patients actually had isolated 
cerebrovascular disease, and the majority (55 percent) had AD upon 
pathological diagnosis. This misdiagnosis can occur because structural 
imaging positively identified incidental infarcts but AD was 
transparent to the study.

Accuracy of Dementia Evaluation With use of PET

    Investigations into clinical applications of PET with dementia 
patients stem from numerous studies that have found that many dementing 
conditions are associated with characteristic alterations in brain 
detectable with molecular imaging of the biology of disease. PET has 
been used in research studies of AD and other forms of dementia since 
the early 1980's, and has been extensively reviewed.
    The best studied application of this type is the use of PET with 
FDG to evaluate AD. Because over 95 percent of the energy (ATP) for the 
brain to function is derived from metabolism of glucose, PET imaging of 
glucose metabolism with FDG provides an excellent way to evaluate 
diseases that disrupt the brain's capability to function normally. By 
the time patients meet clinical diagnostic criteria for AD, widespread 
cerebral metabolic dysfunction is usually already present. FDG-PET can 
thus reveal pathophysiologic alterations associated with AD that occur 
at the earliest stages of clinical dementia. In fact, the 
characteristic alterations in glucose metabolism associated with AD can 
be identified with FDG-PET even before those alterations lead to 
cognitive symptoms. PET studies published in the New England Journal of 
Medicine and Journal of the American Medical Association by different 
university scientists have identified metabolic abnormalities of AD at 
least 5 years before symptoms occur.
    Incorporating molecular imaging with PET into the clinical work-up 
for diagnostic evaluation of dementia could therefore be of 
considerable help in assisting physicians in meeting the challenge of 
diagnosing AD earlier and with greater accuracy. Positron emission 
tomography is of assistance to the clinician in differential diagnosis. 
Distinguishing among the dementias is critical in making decisions 
regarding treatment and management appropriate for Alzheimer's, as well 
as distinguishing which patients who have Alzheimer's from those who 
don't.
    With respect to incremental value of PET beyond clinical 
differential diagnosis, it was recently shown that among patients 
having clinical working diagnoses presuming nonprogressive etiologies 
for their cognitive complaints, those with PET patterns indicative of 
progressive dementia were more than 18 times likelier to experience 
progressive decline than those with nonprogressive PET patterns, 
indicating that the high sensitivity of PET could be used to identify 
the presence of a progressive dementia among those for whom suspicion 
of a progressive dementing illness was otherwise low, and thereby lead 
to earlier institution of appropriate therapy to delay decline.

Conclusion

    A higher rate of earlier and more accurate diagnoses of AD and 
related dementias could be achieved through incorporating PET into 
clinical management, leading to the most appropriate management for 
more patients, which in turn would be associated with substantial 
overall benefit for those patients. It is critically important for 
standard clinical practice to follow the recent advancements in 
clinical research identified by the subcommittee, and for health care 
payors like Medicare to assure that patients and their caregivers have 
access to these best available diagnostic and evaluative tools. We look 
forward to working closely with the subcommittee and the Congress on 
improving both the outcomes and the quality of care received by 
patients with AD and related dementias.

    [Whereupon, at 11:47 a.m., the subcommittee was adjourned.]

                                    

      
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