[Senate Hearing 106-864]
[From the U.S. Government Publishing Office]





                                                        S. Hrg. 106-864
 
                      ALZHEIMER'S DISEASE, PART 2

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

                                HEARING

                                before a

                          SUBCOMMITTEE OF THE

            COMMITTEE ON APPROPRIATIONS UNITED STATES SENATE

                       ONE HUNDRED SIXTH CONGRESS

                             SECOND SESSION

                               __________

                            SPECIAL HEARING

                               __________

         Printed for the use of the Committee on Appropriations




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                      COMMITTEE ON APPROPRIATIONS

                     TED STEVENS, Alaska, Chairman
THAD COCHRAN, Mississippi            ROBERT C. BYRD, West Virginia
ARLEN SPECTER, Pennsylvania          DANIEL K. INOUYE, Hawaii
PETE V. DOMENICI, New Mexico         ERNEST F. HOLLINGS, South Carolina
CHRISTOPHER S. BOND, Missouri        PATRICK J. LEAHY, Vermont
SLADE GORTON, Washington             FRANK R. LAUTENBERG, New Jersey
MITCH McCONNELL, Kentucky            TOM HARKIN, Iowa
CONRAD BURNS, Montana                BARBARA A. MIKULSKI, Maryland
RICHARD C. SHELBY, Alabama           HARRY REID, Nevada
JUDD GREGG, New Hampshire            HERB KOHL, Wisconsin
ROBERT F. BENNETT, Utah              PATTY MURRAY, Washington
BEN NIGHTHORSE CAMPBELL, Colorado    BYRON L. DORGAN, North Dakota
LARRY CRAIG, Idaho                   DIANNE FEINSTEIN, California
KAY BAILEY HUTCHISON, Texas          RICHARD J. DURBIN, Illinois
JON KYL, Arizona
                   Steven J. Cortese, Staff Director
                 Lisa Sutherland, Deputy Staff Director
               James H. English, Minority Staff Director
                                 ------                                

 Subcommittee on Departments of Labor, Health and Human Services, and 
                    Education, and Related Agencies

                 ARLEN SPECTER, Pennsylvania, Chairman
THAD COCHRAN, Mississippi            TOM HARKIN, Iowa
SLADE GORTON, Washington             ERNEST F. HOLLINGS, South Carolina
JUDD GREGG, New Hampshire            DANIEL K. INOUYE, Hawaii
LARRY CRAIG, Idaho                   HARRY REID, Nevada
KAY BAILEY HUTCHISON, Texas          HERB KOHL, Wisconsin
TED STEVENS, Alaska                  PATTY MURRAY, Washington
JON KYL, Arizona                     DIANNE FEINSTEIN, California
                                     ROBERT C. BYRD, West Virginia
                                       (Ex officio)
                           Professional Staff
                            Bettilou Taylor
                             Mary Dietrich
                              Jim Sourwine
                        Ellen Murray (Minority)

                         Administrative Support
                             Kevin Johnson
                       Carole Geagley (Minority)




                            C O N T E N T S

                              ----------                              
                                                                   Page
Opening statement of Senator Arlen Specter.......................     1
Statement of Dr. Richard J. Hodes, Director, National Institute 
  on Aging, National Institutes of Health, Department of Health 
  and Human Services.............................................     2
    Prepared statement...........................................    13
Statement of Dr. Steven DeKosky, director, Alzheimer's Disease 
  Research Center, University of Pittsburgh Medical Center.......    20
    Prepared statement...........................................    22
Statement of Maureen Reagan, member, Alzheimer's Association 
  Board..........................................................    23
    Prepared statement...........................................    25
Opening statement of Senator Tom Harkin..........................    26
    Prepared statement...........................................    27
Statement of Orien Reid, chairman, Alzheimer's Association Board.    27
    Prepared statement...........................................    29
Statement of Frank Carlino, Alzheimer's patient..................    30
    Prepared statement...........................................    31
  


                      ALZHEIMER'S DISEASE, PART 2

                              ----------                              


                        TUESDAY, MARCH 21, 2000

                           U.S. Senate,    
    Subcommittee on Labor, Health and Human
     Services, and Education, and Related Agencies,
                               Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 9 a.m., in room 216, Hart Senate 
Office Building, Hon. Arlen Specter (chairman) presiding.
    Present: Senators Specter and Harkin.


               OPENING STATEMENT OF SENATOR ARLEN SPECTER


    Senator Specter. Good morning, ladies and gentlemen. The 
hour of 9:00 having arrived, the Appropriations Subcommittee on 
Labor, Health, Human Services and Education will now proceed.
    Our hearing this morning is on Alzheimer's disease. This 
subcommittee conducted the first hearing on Alzheimer's disease 
back in 1980, chaired at that time by Senator Tom Eagleton of 
Missouri. Today we continue the subcommittee tradition of 
focusing on this dreaded disease to consider the problems, to 
consider the prognosis, and to analyze ways to improve the 
condition of the some four million Americans who suffer from 
Alzheimer's, a dreaded disease which impacts the individual 
obviously, but the family and all those around him or her.
    The statistics are foreboding for the future. Where we now 
have approximately 4 million Americans suffering from 
Alzheimer's at an annual cost of some $100 billion, the 
projections are as the baby boom generation ages that there 
will be 6 million sufferers of Alzheimer's by the end of the 
decade and 14 million by mid-century, and the cost will have 
ballooned to something like $375 billion.
    The statistics are that 1 in 10 of individuals over 65 and 
50 percent of those over 85 have Alzheimer's disease, which 
takes some 10 to 20 years before the symptoms begin to appear. 
Scientists have developed a vaccine which has promising 
aspects, and there is very intensive work being conducted by 
the National Institutes of Health on the issue.
    Funding has risen consistently, starting in 1976 with $3.9 
million, and the projection this year with the President's 
budget would raise it to $491 million, but that, in the opinion 
of Senator Tom Harkin, my distinguished ranking member, and 
myself, is insufficient. We have allocated very substantial 
additional funds to research in the National Institutes of 
Health by taking a sharp pencil, candidly, to other items on 
the subcommittee's allocation.
    Three years ago we sought to raise the funding by a billion 
dollars, took the issue to the floor and lost 63-37, but we 
found $907 million by paring other accounts. Two years ago we 
decided that a billion was not enough and we decided to raise 
it $2 billion. Again, we lost on a floor vote, but again we 
made allocations from other accounts, because of our concern 
that NIH had that kind of priority, and added some $2 billion.
    Last year we added $2.3 billion, again after losing a floor 
fight and again after reallocating the funds. This year Senator 
Harkin and I have filed a resolution calling for $2.7 billion 
on increase, and the budget committees are now meeting and have 
established a figure of some $596 million for all discretionary 
accounts, which will not leave this subcommittee with enough 
money to continue this juggling act to find $2.7 billion.
    So one of the things that you, ladies and gentlemen, can do 
from all over the country is to identify those Senators who 
voted against increasing NIH and go to see them. We are going 
to make this a short hearing so you will have plenty of time to 
go see all the Senators on Capitol Hill and then to walk across 
the Rotunda and go visit all the House Members who have not 
been willing to provide that kind of funding.
    My personal opinion is that the National Institutes of 
Health are the crown jewel of the Federal Government. In fact, 
I think they are the only jewels of the Federal Government.
    One other item that I want to call to your attention, we 
are about to have a floor fight in the Senate on the use of 
stem cells for research. Stem cells are enormously helpful 
already in a number of ailments--on Parkinson's, on heart 
condition. They may be valuable for Alzheimer's. A stem cell 
replaces a cell in the body and is a veritable fountain of 
youth.
    The controversy has arisen as to whether you can use 
embryos to extract the stem cells. The general counsel for the 
Department of Health and Human Services has handed down a legal 
ruling that Federal funds may be used on the stem cells once 
they are extracted from the embryos, but that makes it very 
difficult for research, and a concern has been raised on 
ethical grounds about using the embryos, but the only kind of 
embryos which are used are discarded embryos, embryos which 
cannot be used to produce human life on in vitro fertilization. 
If there were an issue of morality or use of these embryos for 
human life, I would never agree with that under any 
circumstance.
    It is very similar to the battle we had over fetal tissue, 
on discarded fetal tissue, where for a long time that was not 
used medically, notwithstanding its great potential as a 
curative force. That battle has been won some time ago. When 
Senator Thurmond joined the forces in favor of use of discarded 
fetal tissue, the number of Senators who voted for it rose from 
about 40 to more than 80, and now we are going to have the 
battle over the stem cell issue, so I enlist your support on 
that as well.
STATEMENT OF DR. RICHARD J. HODES, DIRECTOR, NATIONAL 
            INSTITUTE ON AGING, NATIONAL INSTITUTES OF 
            HEALTH, DEPARTMENT OF HEALTH AND HUMAN 
            SERVICES
    Senator Specter. With those introductory remarks, we will 
now turn to our first witness, Dr. Richard J. Hodes, who is the 
Director of the National Institute on Aging. Since 1993 Dr. 
Hodes has served in that capacity. He has also held other posts 
in the National Institutes of Health, including work on the 
National Cancer Institute, a program coordinator for the U.S.-
Japan Cooperative Cancer Research Program and Deputy Chief of 
the Cancers Institute Immunology Branch, graduate of Yale 
University, and an M.D. from Harvard Medical School. It seems 
to me President Kennedy once had something to say about a 
person with degrees from both Harvard and Yale. You may 
proceed, Dr. Hodes.
    Dr. Hodes. Thank you, Mr. Specter, for this opportunity to 
appear with so many Alzheimer's disease advocates and to speak 
to you of the progress that researchers have made in 
understanding and developing interventions for Alzheimer's 
disease and to speak also to the urgency and opportunity for 
future research.
    Senator Specter. Dr. Hodes, as you know, you have been here 
many times, our practice is to limit the opening statements to 
5 minutes. Full statements will be made a part of the record. 
That will leave the maximum amount of time for questions and 
answers.
    Dr. Hodes. I will certainly do my best to meet with those 
time limitations. As you so adequately described, Alzheimer's 
disease is a progressive disease caused by abnormal changes in 
the brain which ultimately affect memory, cognitive function, 
personality, behavior, with devastating consequences for those 
afflicted as well as family members, loved ones, and society.
    Tragically some 4-million Americans are currently affected 
with the disease, a disease which has an enormous age 
dependence. That is illustrated in the first poster which 
describes, much as you have summarized, the results of studies 
showing that the prevalence of Alzheimer's disease increases so 
dramatically with age until in the group 85 and over, some 47 
percent or nearly half are afflicted.
    This, combined with census projections for an increase in 
this vulnerable population 85 and over to some 20-million 
Americans at that age group at risk by the middle of this next 
century, create a really impending public health threat to us 
all.
    In the face of that, NIA, NIH, the Alzheimer's Association 
are all committed to pursuing research aimed toward preventing 
these dire projected consequences. In the context of what we 
understand about Alzheimer's disease now, we can model its 
progression really into four stages. The first of these is that 
of the normal brain, with no symptoms and no lesions, which 
first progresses to presymptomatic Alzheimer's disease. That is 
the case in which there are no manifestations clinically but 
where we now understand there are changes in the brain.
    The next stage is that of mild cognitive impairment, still 
not dementia, not Alzheimer's disease, but one in which 
symptoms of memory loss can be determined and in which again 
there is progression of certain detectable lesions in the 
brain, and then finally, the fourth, last stage, that of 
diagnosed Alzheimer's disease.
    Until recently all interventions were directed exclusively 
at treating and attempting to slow the progression of already 
developed Alzheimer's disease. However, now armed with results 
of recent scientific discovery, we are for the first time able 
to attempt interventions prior to the onset of the disease in 
an effort to slow or prevent its progression.
    With the recognition of our current opportunities, Congress 
recently provided us with language encouraging NIH to launch an 
Alzheimer's disease prevention initiative. The NIA, as the lead 
agency, is working with other NIH institutes, other Federal 
agencies, and important public and private partners such as the 
Alzheimer's Association.
    This initiative has as its charge the intensification of 
basic research and the translation into interventions to 
prevent or slow the progression of Alzheimer's disease. In that 
effort, we recently last year were able to initiate the first 
large-scale prevention trial at NIA, one in which some 65 
institutions will recruit individuals with mild cognitive 
impairment, that is, without Alzheimer's disease but at high 
risk to develop it, and will attempt to test the interventions 
in this case of vitamin E and Donepezil to see if they can 
alter the progression of the disease.
    Similar studies will be undertaken looking at agents 
including nonsteroidal anti-inflammatories, estrogen, and a 
newly initiated study in collaboration with the National Center 
on Complementary and Alternative Medicine, a study to look at 
the effects of ginkgo biloba in that regard as well.
    The clues for further discovery in Alzheimer's disease come 
from basic science. An example of basic science discovery in 
the past year which has really revolutionized and opened our 
eyes to further opportunities is illustrated in this 
transparency.
    In contrast to what was the widely held belief until just 
the most recent years, it is possible in the human brain, and 
the brains of experimental animals as well, in adults, even 
older adults, for the brain to generate new cells. In the panel 
at the left, what the figure illustrates is that in young mice 
or in older mice there is a capability to generate new brain 
cells, and strikingly, as can be seen in the difference between 
those higher blue bars and the lower red bars, the rate of 
generating new brain cells, in fact, can be stimulated by in 
this case an enriched environment in which both physical and if 
you will intellectual challenges are posed to experimental 
animals, providing an intriguing model for the effect of such 
interventions in humans as well.
    The figure at the right illustrates in those cells that 
appear green that even in the human brain, in fact, in adults, 
the generation of new brain cells can occur. This ability to 
stimulate, to provoke the generation of brain cells provides a 
new approach that will be translated in the future into 
interventions designed to either arrest or reverse some of the 
effects of Alzheimer's disease.
    Similarly in other areas a convergence of both 
epidemiologic and basic science studies has provided us with 
new approaches to intervention. The next and last of the 
illustrations is the example for nonsteroidal anti-
inflammatories.
    On the left is an illustration from epidemiologic 
observations, indicating that those individuals who have a 
history of using nonsteroidal anti-inflammatories, such as 
Ibuprofen, for a variety of reasons have approximately a 50-
percent reduction in the rate of Alzheimer's disease. So far, a 
correlation not demonstrated to be due to the causal effects of 
those interventions.
    This observation is coupled, however, with what you can see 
on the right, a panel showing these networks of inflammatory 
cells surrounding Alzheimer's lesions. This convergence of 
evidence again will lead and has led to the initiation of 
studies to test the effects of such anti-inflammatories in 
preventing the development and progression of Alzheimer's 
disease.
    Senator Specter. Dr. Hodes, did you say that there has not 
been a causal connection established?
    Dr. Hodes. That is right. It is important to note that when 
epidemiologic studies are carried out, they identify 
correlations or associations, in this case a strong 
association.
    Senator Specter. Why do you not define an epidemiological 
study for our C-SPAN viewers?
    Dr. Hodes. I would be happy to. An epidemiologic study is 
one which examines in a population the behavior, the incidence 
of a given condition.
    Senator Specter. Everybody in the audience knows it, but C-
SPAN viewers may not.
    Dr. Hodes. What epidemiology is able to do is to track the 
correlations or associations--in this case to find whether 
there are particular factors which place individuals at greater 
or lower risk for Alzheimer's disease. Finding that people who 
have had a history of taking a drug such as anti-inflammatories 
had a lower risk of Alzheimer's disease means there is an 
association, but it does not prove that taking those drugs is 
what caused the decrease in Alzheimer's.
    Senator Specter. What is the statistical base or 
evidentiary base for finding a lower incidence of Alzheimer's 
from those who take these drugs?
    Dr. Hodes. Well, the data shown here result from 
observations in the Baltimore Longitudinal Study on Aging which 
followed individuals over decades of their lives.
    Senator Specter. Longitudinal study on aging?
    Dr. Hodes. That is right, in order to determine----
    Senator Specter. What is a longitudinal study on aging?
    Dr. Hodes. A longitudinal study is one which follows the 
same individuals successively over time. That is the 
longitudinal dimension. So in this case some hundreds, now 
thousands of individuals have been followed for many years, in 
some cases many decades, so that it is possible to observe not 
just a cross-section, a snapshot of their condition, but 
changes that occur over time. In this case, including changes 
in cognitive function and in some the development of 
Alzheimer's disease.
    Senator Specter. And by cognitive function you mean?
    Dr. Hodes. A variety of functions, the most commonly 
measured of which is memory in its various subtypes. The 
ability to recall, the ability to use recalled information as 
well.
    Senator Specter. And you find from the observation of those 
people that there is an effect from the drugs?
    Dr. Hodes. Again there is a correlation, yes, which is----
    Senator Specter. And correlation to what extent?
    Dr. Hodes. It means that if you take a look at people who 
have had a history of using these drugs and those who have not, 
that those individuals who have used the drugs, in this case, 
have only half the rate of Alzheimer's disease compared to the 
individuals who have not had any such history of drug use.
    Senator Specter. But that is not sufficient for you to come 
to a scientific conclusion of a causal connection?
    Dr. Hodes. It is not. It is suggestive and compelling data 
which has provoked the institution of direct, controlled 
clinical trials. In these trials, a group of individuals who do 
not have Alzheimer's disease but are at high risk to develop it 
are divided into two groups.
    Senator Specter. What do you look for before you would move 
from suggestive and compelling to a causal connection, 
conclusion?
    Dr. Hodes. Well, the first step is to identify the 
correlative and basic science information, determine whether it 
has reached a critical mass so that it is sufficiently 
suggestive to warrant a clinical trial.
    Senator Specter. A relative and critical mass. And by that 
you mean?
    Dr. Hodes. I mean that the judgment of expert scientists is 
applied to look at in this case epidemiological studies as well 
as basic science studies and determine whether they together 
are sufficiently compelling of a likely effect of the drug to 
warrant a direct test of that effect in clinical trial.
    Senator Specter. So how much evidence do you need to come 
to a conclusion that there is a causal connection between the 
drug and the beneficial effect?
    Dr. Hodes. Well, to this point the gold standard, the most 
rigorous test that we can apply to that question is the 
controlled clinical trial. In a study such as this, a group of 
individuals who are at risk for disease are divided into two 
groups, groups that either receive the treatment being tested 
or some alternative--in this case a placebo, a sugar pill. The 
individuals do not know which group they are in, the physicians 
taking care of those individuals do not know which group they 
are in, and at the conclusion of the study, which involves 
following these individuals for months and years, there is a 
determination made of how many of those individuals have had a 
loss in cognitive function, how many have developed Alzheimer's 
disease, and only then does one uncode the results to see 
whether, in fact, the group that is involved in the active 
treatment, in this case anti-inflammatories, has had a reduced 
rate of development of Alzheimer's disease compared to the 
control group.
    Senator Specter. Well, what are you looking for, again, 
before you would say that there is a causal connection? What 
level of proof?
    Dr. Hodes. Well, any differences that might arise from a 
clinical trial such as this are presumably due to the 
difference in what the subjects took--the drug or the control. 
Whether that test is a definitive one depends upon some very 
complex and austere statistical calculations, to make certain 
that at the level of high probability, that the difference in 
any groups that is seen is not due to chance but truly could 
have come only from the difference in the treatments for those 
individuals.
    Senator Specter. I will try one more time. How high does 
the probability have to be before you say it is causal?
    Dr. Hodes. Well, I apologize for ourselves, scientists and 
statisticians, who answer those questions rather 
quantitatively. Traditionally if we can find----
    Senator Specter. If you do that, I will apologize for us 
lawyers who ask the questions.
    Dr. Hodes. The results of studies can be analyzed. In a 
typical finding of a study to be interpreted to be positive, we 
say there is no more than a 100-to-1 chance that such a result 
could have occurred by coincidence alone, so the level of 
certainty in that case is at least 100 times that of a chance 
and coincidental observation.
    Senator Specter. Dr. Hodes, when you run these tests and 
you give some people the real McCoy, and you give some people 
the placebos, by which you mean a sugar-coated tablet, so they 
think they may be getting something psychologically but they 
are really not, there is obviously a benefit for that group 
which receives the medicine. And I am sure you tell or perhaps 
I should ask you the question, do you tell everybody in the 
group that some will be receiving the medicine and some will be 
receiving placebos, so that they know that they may not be 
getting a medicine which would benefit them, but are just part 
of a test group getting a placebo which will probably do them 
no good?
    Dr. Hodes. You have addressed some extremely important 
points. And quite absolutely, it is ethically imperative that 
subjects who enter such a study understand precisely what the 
circumstance is and understand that they have a chance of 
receiving either the test medication or the placebo.
    What I need to point out, however, is that somewhat in 
contrast to your remarks, that it is obviously to the advantage 
of those taking the drug to be in that group. The very 
rationale for carrying out these studies is one in which we 
simply do not know if the drug is effective or not. If we 
believe that we were withholding an agent that was known to be 
effective from one group, ethics would simply prevent us from 
conducting the trial. But generally as these trials are carried 
out we do not know if a drug will be effective. We even have to 
be open to the possibility it will have a negative or adverse 
effect, so the ethics are very important.
    The patients are well informed. In the case of patients 
involved in studies such as these, both A, their families, 
their surrogates are also well informed of the nature of the 
study's design and are kept informed during the study of its 
outcomes as well.
    I should add that we also monitor the trials, and as soon 
as it becomes evident, if it were to, that a given treatment is 
effective at a sufficient level of certainty, the study is then 
terminated. Certainly we would not continue to treat people in 
such a way as to withhold an agent of known effectiveness.
    Senator Specter. How long does that customarily take? It 
can be a very protracted period of time, can it not?
    Dr. Hodes. It can. The length of clinical trials, of 
course, depends upon how quickly people who are not being 
treated develop the disease. In the case of Alzheimer's trials, 
the length of treatment is typically in the range of 1, 2, or 3 
years depending upon the group and the rate of progression of 
disease.
    Senator Specter. Dr. Hodes, is it possible to make a 
determination through gene testing as to whether an individual 
has an inclination or the risk of Alzheimer's?
    Dr. Hodes. In the past decade we have learned a great deal 
about the genetic influences on Alzheimer's disease, and it is 
important to distinguish there are a relatively small 
subpopulation of Alzheimer's cases, perhaps 10 to 15 percent, 
with what has been termed familial early onset Alzheimer's 
disease. In the case of that group there is a rather clear 
correlation between having a particular gene disposing disease 
and developing Alzheimer's. Again, I emphasize this is a very 
small subset, typically people who know they have a strong 
family history of the disease with early onset. In those cases 
genetic testing can identify individuals who are likely if not 
destined to develop the disease. However, for the great 
majority of cases, some 85 percent or so, there is no clear 
causal association.
    There are, however, certain genetic types, alleles, ApoE4 
is one that has received a lot of attention, which can increase 
the risk of an individual to developing disease, but the 
presence or absence in that case of that gene is not any 
guarantee that an individual either will or will not have the 
disease.
    Senator Specter. Well, since there are some steps which can 
be taken, as you have described them, to treat Alzheimer's at 
an early stage, would you recommend that an individual undergo 
genetic testing to see if there is a proclivity for it, to get 
some help in advance to try to prevent it or slow it down?
    Dr. Hodes. This is a challenging, complex question that has 
received a good deal of attention and deliberation. In the 
instance of the nonfamilial Alzheimer's disease, current 
recommendations do not support the use of genetic testing, 
except in a research setting or in the hands of a physician as 
an adjunct to other diagnostic tests, but the simple 
determination that one does or does not have, for example, an 
ApoE4 allele in and of itself does not have sufficiently strong 
implications----
    Senator Specter. ApoE4 allele?
    Dr. Hodes. Yes.
    Senator Specter. Well, there are some people even in this 
audience who do not know what that means.
    Dr. Hodes. Yes.
    Senator Specter. Would you define it?
    Dr. Hodes. Yes. ApoE is an abbreviation for, this will not 
help you a lot, I apologize, Mr. Specter, apolipoprotein E, 
which is a substance that was first identified to be important 
in carrying lipids, fats in the blood. Individuals, different 
individuals in the population have a different form or 
variation of this ApoE gene. One of those forms, ApoE4, is 
correlated with an increased risk of Alzheimer's disease. 
Individuals who carry that type compared to those who do not 
have in various studies a two- or three- or so-fold increase in 
the likelihood of developing the disease.
    Senator Specter. Can you quantify the increased likelihood 
for developing Alzheimer's disease with ApoE4 allele?
    Dr. Hodes. Yes. If a series of individuals are typed to see 
whether they do or do not have the ApoE4 and then are studied 
for the likelihood of developing Alzheimer's disease, in 
certain populations--and it really does vary, it appears now, 
with which population one is concerned with--in certain 
populations there is a severalfold, in the range of 3- or 4-
fold increase in the likelihood----
    Senator Specter. Three or four times?
    Dr. Hodes. Yes.
    Senator Specter. So why not test people? That is a fairly 
high incidence. If 1 person out of 10 over 65 gets it and if 
you find a three or four times likelihood--the whole field of 
genetic testing is scary, really. People test like they are 
getting their exams all at once, to find out what you have a 
risk of getting, and it is really in the beginning stages, but 
if there is a material chance of helping people not develop the 
disease or retard it, it seems to me that is something that 
people ought to be told about and at least have the option of 
doing. The recommendation may or may not be determinative, but 
that is a factor which I think could really stand some 
publicity.
    What efforts are being made to publicize the availability 
of this kind of genetic testing to militate or to work against 
developing Alzheimer's disease?
    Dr. Hodes. Well, in fact, as I had mentioned, the 
particular issue of genetic testing and Alzheimer's disease was 
the subject of an extensive conference involving scientists, 
ethicists, which led to the recommendation that at the present 
time, given the incomplete state of our understanding of what 
causes the disease and what can be done to prevent disease, 
that the use of this genetic testing is appropriate only in the 
context of clinical trials or in association with other 
diagnostic measures being employed by a physician or caregiver. 
This is a situation which we clearly need to revisit 
constantly.
    If we were, for example, to arrive at the point of having 
clearly demonstrable effective treatments to prevent the 
advance of Alzheimer's disease, then the imperative, the 
appropriateness for genetic testing to find out who was at a 
greater risk would certainly be reassessed.
    Senator Specter. Dr. Hodes, when this subcommittee takes 
the lead in increasing the funding for the National Institutes 
of Health, we are constantly being questioned about how 
effective this increase in funding is. Are we increasing the 
funding too fast?
    The funding for Alzheimer's has gone up in the last 5 
years. In 1997 it was $329 million; in 1998, $356 million; 
1999, $406 million--big jump there. And a bigger jump in 2000, 
$466 million. What has been the effect of this increase in 
funding? Is it worth it? What has been determined? What can you 
say which will persuade my colleagues in the Senate and the 
House that these substantial increases are producing some 
tangible results or the prospects of tangible results?
    Dr. Hodes. These increases, in the case of Alzheimer's 
disease research, have occurred at a time when scientific 
opportunities are expanding and have expanded at an 
unprecedented rate. Not only has basic science and discovery 
led to opportunities for interventions to treat and prevent, 
but it has now produced a generation of clinical trials which 
are exciting and are also extremely expensive. The kinds of 
trials that I have mentioned--that you will hear further 
commented upon this morning, designed to test the ability of 
agents to prevent the development of Alzheimer's disease--
require large numbers of individuals, trials that are expensive 
to conduct, but are the most critical hope for our finding a 
way to prevent or delay the onset of Alzheimer's disease.
    Senator Specter. Well, scientists have developed a vaccine 
which appears to stop in the brains of mice the formation of 
these plaques. The enzyme has been identified implicated in the 
formation of the plaques. Can you give us any other specific 
results which have been achieved from this increase in funding?
    Dr. Hodes. Yes, I can certainly comment on those 
discoveries which you have mentioned. As you have said, in mice 
there is now an intriguing model in which immunizing against 
amyloid, the material that occurs in the plaques of Alzheimer's 
disease, can reduce those lesions in mice.
    Now the process begins of looking to see whether those 
interventions will work and are safe in other animal models 
before ultimately considering their application to humans. As 
you have mentioned, some of the basic biology of what is 
responsible for causing amyloid plaques has been uncovered, so 
these two new enzymes that you alluded to, secretases, have now 
been shown to affect the production of amyloid in tissue 
culture or in vitro.
    Now the critical determination is whether there are ways 
that one can intervene to block those enzymes and determine 
whether that will have an effect, both first in experimental 
animal model systems and ultimately whether they can be 
translated into clinical studies or interventions.
    Senator Specter. Besides those items, can you specify other 
advances as a result of this increased funding?
    Dr. Hodes. The other major lesion that occurs in the brains 
of those individuals with Alzheimer's disease are the so-called 
Tau lesions or tangles. Only in the past year to two has it 
been identified both that mutations in Tau can be associated 
with disease in humans and that animal models can be generated 
to reproduce the effect of expressing abnormal Tau upon, 
generating a potential additional animal model for Alzheimer's 
disease.
    In addition to this basic science, as we talked about 
prevention, the discovery of new ways to diagnose disease early 
has been critical. One of the areas in which progress has been 
made in recent years has been that of brain imaging. It is 
possible now in individuals who are not yet symptomatic with 
Alzheimer's disease to analyze the both function and structure 
of parts of the brain with now, suggestions being provided of 
changes in the brain of as-yet-asymptomatic patients which are 
predictive of a higher risk for developing Alzheimer's disease. 
That is critical both for understanding the process and for 
identifying individuals who are at the highest risk for 
Alzheimer's disease and who are candidates for interventions.
    Senator Specter. May the stem cell research ultimately have 
some impact on Alzheimer's disease, in your opinion?
    Dr. Hodes. I think that the promise of stem cell research 
is extremely high, and there are many kinds of stem cells, as 
you alluded to earlier. The slides which I used to illustrate 
the generation of new brain cells in adults in effect are 
indicating the potential for stem cells already within the 
body, within the brain, to be used, to be mobilized to generate 
additional and new functional brain cells. In addition, 
techniques for transplanting stem cells, neural stem cells, 
stem cells of other origin, are under intense experimental 
application at present as well.
    Senator Specter. So stem cell research is being applied to 
Alzheimer's as well as other ailments?
    Dr. Hodes. It is.
    Senator Specter. The Alzheimer's Association is looking for 
a $100 million increase. They would like to bring the figure up 
to $566 million. It is well known from the large group here 
attending, this is--this hearing coincides--this hearing was 
scheduled really to coincide with the 12th Alzheimer's 
Association public policy forum. We scheduled it for this 
purpose because everybody is in town today.
    Give me your best reasoning why their request for $100 
million would have a significant impact over and above what the 
President has recommended, which is only $491 million, $75 
million less than the Association is looking for.
    Dr. Hodes. Well, we have clearly been able to make 
substantial progress with the budget allocations of past years, 
but I think it is also clear that the scientific opportunities 
are such that we have not been able to fund all of the 
meritorious and promising research that has been proposed to us 
by the scientific community. This includes the kinds of 
research which could be expanded with a yet additional budget 
increase, both in the basic science, where it is important to 
continue to discover the underlying causes, and to take 
advantage of those discoveries by funding additional what we 
call translational activities that involves ways to find better 
diagnostics early in the case of the disease to be able with 
techniques such as imaging to be able to uncover the disease.
    It involves the ability to carry out more than one, two, or 
three clinical trials concurrently. At a time when the 
epidemiology and the demography point to the real threat of a 
burgeoning population with this devastating disease, we do feel 
this urgency to carry out clinical trials on as many fronts as 
are promising concurrently, simultaneously, to increase the 
probability that one or more of these will be successful in 
time to arrest disease for many of those at risk today.
    Senator Specter. Five years ago we were told that about 28 
to 34 percent of the grant applications were receiving awards, 
and even though we have increased the funding enormously, right 
at $18 billion now from less than $13 billion, we are told that 
still only about a third of the grant applications receive 
awards. That is because with the increased funding there are 
more people out there who are submitting grant applications, 
and that is good, but we have three doors, and we are only 
opening one of them on the grant applications.
    Should we be giving awards to more? They are probably not 
all meritorious, but probably more than one out of three is 
meritorious. What would be the real funding level that you 
would like to see to make awards to all of the worthy grant 
applications?
    Dr. Hodes. Mr. Specter, to reinforce what you said, I can 
comment that last year the success rate at the National 
Institute on Aging was approximately 28 percent. This year, 
despite the substantial budget increases, it is estimated to be 
about 22 percent. At the level of the President's budget----
    Senator Specter. You are making more grants, though?
    Dr. Hodes. Yes.
    Senator Specter. There are more applications?
    Dr. Hodes. Well, yes. But both this downward trend and the 
projected decrease to 17 percent with the President's budget 
reflect both an increase in the number of applications, but at 
least as importantly, the increased average cost of these 
research projects. As I have mentioned, as we have the 
opportunities, the exciting opportunities to turn to clinical 
interventions, the cost of these studies also increases and has 
an influence on the proportion of grants that can be funded.
    Senator Specter. How much money would you like to have for 
Alzheimer's research, Dr. Hodes?
    Dr. Hodes. Our professional judgment budget as expressed 
has proposed an increase in the range of some 15 percent, which 
is a range we would most appropriately like to see continue 
with continuity from year to year.
    As I know you have heard in previous testimony, what is 
extremely difficult for the pursuit of science is to have an 
unstable base, an increase one year and none the next, and the 
fostering of productive science is certainly best accomplished 
with a consistent and reliable expectation of increase.
    Senator Specter. Well, as long as Senator Harkin and I are 
here to make it bipartisan, you will get the increases.
    Dr. Hodes. Thank you, sir.
    Senator Specter. If I had known that was going to be an 
applause line, I would have said it a lot earlier. Well, that 
is the question. You talk about 15 percent, and 15--I know your 
point on consistency, and I agree with it. We talk about 15 
percent, all this goes through the Office of Management and 
Budget. So it is all pared down. The scientific views do not 
really come through OMB. Almost nothing comes through OMB. That 
is why we probe beyond that.
    The current budget, Senator Taylor tells me, is $17.8 
million. That is a lot of money but not necessarily a lot of 
money on a budget of $1,850,000,000,000. So the question comes 
back as to how many of those doors would you like to open. When 
you are dealing with a life and death, those are very high 
stakes. So we would appreciate your supplemental evaluation as 
to how many of those grants--you are now awarding only 22 
percent, so 78 doors out of 100 are not being opened.


                           PREPARED STATEMENT


    I would like to have the answer to specific questions. One 
is, how many of those other 78 doors ought to be opened, and 
what would it cost? Anything further, Dr. Hodes?
    Dr. Hodes. No. Thank you very much for this opportunity.
    Senator Specter. OK, thank you.
    [The statement follows:]
                 Prepared Statement of Richard J. Hodes
     Mr. Chairman and Members of the Committee: Thank you for inviting 
me to appear before you today on an issue of mutual interest and 
concern, Alzheimer's disease. I am Dr. Richard Hodes, Director of the 
National Institute on Aging (NIA), the lead federal agency for 
Alzheimer's disease (AD) research. It is an honor to share with you 
information about the progress researchers are making to understand, 
treat, and prevent Alzheimer's disease.
    If this hearing were being held ten years ago, the message would 
not be as promising. While there is still significant work to be done, 
the unprecedented pace of recent discoveries holds great promise for 
conquering this devastating disease. In the last decade, researchers 
have made tremendous strides toward solving the mystery of Alzheimer's 
disease, improving understanding of its underlying molecular processes, 
developing innovative diagnostic tools, devising effective treatments, 
and testing prevention strategies.

                    ALZHEIMER'S DISEASE: AN OVERVIEW
    Alzheimer's disease, the most common cause of dementia among older 
persons, is the result of abnormal changes in the brain that lead to a 
devastating decline in intellectual abilities and changes in behavior 
and personality. AD eventually leaves patients unable to perform even 
the most basic tasks, with devastating consequences to individuals, 
families, and society. Scientists do not yet fully understand what 
causes AD, but it is clear that AD develops as a result of a complex 
cascade of events, influenced by genetic and non-genetic factors, 
taking place over time inside the brain with age being the most 
prominent risk factor. These events cause the brain to develop beta 
amyloid plaques and neurofibrillary tangles and lose nerve cells and 
the connections between them in a process that eventually interferes 
with normal brain function.
    Tragically, as many as four million Americans \1\ \2\ now suffer 
from Alzheimer's disease, and an estimated 360,000 new cases will occur 
each year.\3\ Research has revealed that the prevalence of AD doubles 
every five years beyond the age of 65, meaning dramatic increases in 
the number of new cases as the population ages. Being able to 
articulate the magnitude of Alzheimer's disease is a fairly recent 
development. In 1989, researchers working in East Boston completed a 
landmark epidemiologic study, which concluded that approximately ten 
percent of those over 65 and almost fifty percent of the community-
based population aged 85 and older have possible Alzheimer's disease 
(Chart #1). This finding, coupled with current Census Bureau 
projections that indicate there will be 20 million people in the United 
States aged 85 or older by 2050 \4\ at risk for AD, makes Alzheimer's 
disease a very serious, impending public health threat. The NIH 
recognizes the urgency of this threat and is committed to supporting 
critical bench to bedside research, including basic, clinical, and 
behavioral research, to improve AD diagnosis, treatment, and patient 
care, and to delay, and eventually prevent, the onset of this 
devastating disease.
---------------------------------------------------------------------------
    \1\ Evans, D.A., Estimated prevalence of Alzheimer's disease in the 
U.S. Milbank Q. 1990;68:267-289.
    \2\ Advisory Panel on Alzheimer's Disease. Alzheimer's Disease and 
Related Dementias: Acute and Long-term Care Services. Washington, DC: 
U.S. Dept. Of Health and Human Services; 1996. NIH publication. 96-
4136.
    \3\ Brookmeyer, R, Gray, S, Kawas, C., Projections of Alzheimer's 
Disease n the United States and the Public Health Impact of Delaying 
Disease Onset, AJPH, 88(9), 1337-1342, 1998.
    \4\ Bureau of the Census, Middle Series Projections, 1996.
---------------------------------------------------------------------------

           THE NIH ALZHEIMER'S DISEASE PREVENTION INITIATIVE
    Advances in our understanding of AD in recent years have been 
substantial, including an enhanced understanding of the ways in which 
Alzheimer's disease develops. We can model the progression from normal 
function to clinically diagnosed AD through four distinct phases: (1) 
normal (no disease or symptoms); (2) pre-symptomatic (early brain 
changes, no symptoms); (3) mild cognitive impairment (memory deficit 
without dementia); and (4) diagnosed AD (mild, moderate to severe 
(Chart #2). Earlier clinical research efforts on AD focused on slowing 
worsening of symptoms among patients who had been diagnosed with AD. 
Armed with new knowledge, researchers, for the first time, are now 
developing and testing potential interventions to prevent the disease 
among persons with mild cognitive impairment and among those with no 
symptoms.
    Capitalizing on scientific opportunity, Congress supported language 
in the fiscal year 2000 NIH appropriations report, encouraging the NIH 
to establish an Alzheimer's Disease Prevention Initiative. NIA, on 
behalf of the NIH, was asked to lead this initiative and to collaborate 
with other Federal agencies, including other NIH Institutes (most 
notably, the National Institute of Mental Health, National Institute of 
Neurological Disorders and Stroke, and National Institute of Nursing 
Research) and the private sector in its implementation. Later this 
month, the NIA once again will be chairing a meeting of the Ad Hoc 
Interagency Committee on Research on Aging, an organization comprised 
of almost 40 federal agencies interested in various aspects of aging 
research, to further discuss how the NIA may expand interagency 
collaboration of this important initiative.
    The goals of the NIH AD Prevention Initiative are to: invigorate 
discovery of new treatments, identify risk and preventative factors, 
enhance methods of early detection and diagnosis, advance basic science 
to understand AD, improve patient care strategies, and alleviate 
caregiver burdens. The initiative is also focused on accelerating 
movement of promising new treatments and prevention strategies into 
clinical trials and improving understanding of normal brain function.
    The NIA kicked off a major component of the AD Prevention 
Initiative last year by launching the first large-scale AD prevention 
clinical trial supported by the NIH, the Memory Impairment Study (MIS). 
The trial, which is being conducted at more than 65 medical research 
institutions in North America, including the 28 NIA-supported 
Alzheimer's Disease Centers, is evaluating vitamin E and donepezil 
(Aricept) over a three-year period for their effectiveness in slowing 
or stopping the conversion from mild cognitive impairment (MCI), a 
condition characterized by a memory deficit without dementia, to AD. 
Other ongoing or upcoming AD prevention trials will examine the 
effectiveness of naproxen and celecoxib, a Cox-2 inhibitor, (anti-
inflammatory drugs), in reducing the development of AD, and whether 
treatment with a variety of agents, such as aspirin, vitamin E, 
antioxidants, or combined folate/B6/B12 supplementation can prevent AD. 
The effects of each of these agents on normal age-related decline will 
also be evaluated. In addition, the NIA is co-funding a new clinical 
trial with the National Center on Complementary and Alternative 
Medicine that is testing the effects of ginkgo biloba, a readily 
available natural product, to determine whether it can delay or prevent 
dementia in older individuals. Information about ongoing clinical 
trials and recruitment opportunities is available to the public through 
the NIA-supported Alzheimer's Disease Education and Referral Center web 
site (www.alzheimers.org) and toll-free number (1-800-438-4380).

                       IMPROVING DIAGNOSTIC TOOLS
    Clinicians use a variety of tools to diagnose AD in patients 
experiencing difficulties with memory or other mental functions. These 
tools include patient history, physical exam, laboratory tests, brain 
scans, and a series of tests that measure memory, language skills, and 
other abilities related to brain function. However, at this time, AD 
can be diagnosed conclusively only by examining the brain post-mortem. 
Yet, the tremendous progress that researchers have made in developing 
accurate diagnostic tests and techniques is making it increasingly 
possible for probable AD to be diagnosed at earlier stages. In 
specialized research facilities, including the NIA-supported 
Alzheimer's Disease Research Centers, clinicians can now diagnose AD 
with up to 90 percent accuracy.
    The ability to assess the effectiveness of early treatments or 
interventions, such as those being tested in the AD Prevention 
Initiative, will be enhanced by our ability to observe brain function 
using new imaging techniques. In a recent study, investigators used 
magnetic resonance imaging (MRI) to determine volume measurements of 
the hippocampus, one of the regions of the brain responsible for memory 
function, in individuals diagnosed with mild cognitive impairment 
(Chart #3). Based on three years of observations, researchers found 
that in older people with MCI, the smaller the hippocampus at the 
beginning of the study, the greater the risk of developing AD later. 
This imaging study illustrates how abnormal cerebral function or 
anatomy could be used to aid in detecting the onset of AD before 
clinical diagnosis of AD, and how diagnostic advances can help ensure 
the effective application of emerging early interventions. Advances in 
imaging techniques also have important diagnostic implications for 
other neurodegenerative diseases, such as Parkinson's disease.

       BENCH TO BEDSIDE: THE PATH FROM BASIC SCIENCE TO TREATMENT
    Developing effective treatments for AD based on advances in basic 
research is a major focus of NIA-supported studies. The ability of 
researchers to conceptualize effective treatments was enhanced by the 
discovery of enzymes called secretases that are involved in the 
clipping of a normal cell surface protein to produce the amyloid 
peptide that forms the senile plaques found in the brains of AD 
patients. Identifying and understanding how these enzymes work will 
accelerate the development of interventions to specifically block their 
action and stop the development of AD plaques. NIA will also support 
research to evaluate the potential of an immunization approach recently 
developed by researchers in the private sector, which, in mice, 
prevented the formation of amyloid plaques associated with AD.
    Tau is a protein that is associated with the development of the 
neurofibrillary tangles characteristic of AD. A transgenic mouse strain 
that expresses a human tau gene and develops AD-like tau tangles has 
been developed. This model will help scientists understand how tau 
produces AD in the brain, and together with other AD models, will move 
researchers closer to developing effective preventive or treatment 
interventions. In another study, researchers demonstrated that 
shrinkage and dysfunction of certain brain cells that occur with age 
might be reversible. Researchers inserted into skin cells a gene that 
makes human nerve growth factor (NGF) and then injected the modified 
cells into the brains of experimental animals. After three months, the 
older animals injected with NGF-expressing cells had brain cells that 
resembled those of younger animals. Such gene transfer approaches to 
recovering cellular function could eventually have important 
implications for the treatment of AD and other chronic age-related 
neurodegenerative disorders in humans.
    Another exciting advance with great promise has overturned long-
held beliefs that cells of the adult brain cannot reproduce (Chart #4). 
Investigators have shown that rodents, non-human primates, and humans 
make new, mature brain cells, even in older adults, in the hippocampus, 
an important area of the brain for learning and memory. Intriguingly, 
the studies also showed that more new brain cells survived in mice 
exposed to stimulus-enriched environments than in those housed in a 
conventional laboratory environment for both young and old mice. Other 
research shows that stress can substantially reduce the production of 
new brain cells. These findings are major steps forward, opening the 
way to enhancing nerve cell development and to the possibility of 
replacing nerve cells lost through age, trauma, or disease.
    The convergence of evidence from basic laboratory science and 
epidemiology studies has also led to the identification of candidate 
interventions that may treat or prevent AD. Chart #5 illustrates 
findings from an epidemiologic study in which it was observed that 
individuals who reported taking nonsterodial anti-inflammatory drugs 
(NSAIDS), such as ibuprofen, had a decreased risk of AD (Chart #5). In 
basic research studies, investigators have uncovered evidence that 
inflammation occurs in association with the lesions found in the brains 
of patients with AD, suggesting a possible role for anti-inflammatory 
agents in the treatment of AD. Similarly, both basic and epidemiologic 
studies have suggested a possible role for estrogen in protecting 
against development or progression of AD. Basic science investigators 
have observed the effect that estrogen can have on stimulating neuronal 
growth, and epidemiologists have observed an association of estrogen 
replacement use in post-menopausal women with a decreased risk of AD 
and enhanced cognitive function (Chart #6). As a result of these 
observations, the NIA is supporting studies to test NSAIDs and estrogen 
as potential treatments and preventative agents against Alzheimer's 
disease. These investigations include a multi-site study launched in 
2000 to determine whether treatment with certain NSAIDs will slow 
cognitive and clinical decline in AD patients, and an ongoing study 
launched in 1999 to determine the effect of estrogen replacement 
therapy in preventing AD in women with a family history of the disease. 
The NIA looks forward to sharing the results of these studies with 
Congress and the public and, most importantly, to playing a role in 
helping translate the results of any promising basic and epidemiologic 
studies into effective, safe treatments for testing in clinical trials.

                PROMOTING DRUG DISCOVERY AND DEVELOPMENT
    The only currently FDA-approved treatments for AD are tacrine and 
donepezil. However, there are currently 50 to 60 drugs in the pipeline 
in various stages of testing that have shown promise in either treating 
the symptoms associated with AD or slowing the progression of the 
disease. The National Institute on Aging has developed ongoing programs 
to promote the discovery, development, and testing of compounds to 
alter (by reducing, slowing, or reversing) the cognitive and behavioral 
manifestations of Alzheimer's disease and eventually to delay the onset 
or prevent Alzheimer's disease entirely.
    The NIA-supported Drug Discovery for the Treatment of Alzheimer's 
Disease initiative focuses on the preclinical discovery and development 
of novel compounds for the treatment of the cognitive impairment and 
behavioral symptoms associated with Alzheimer's disease. Potential 
therapeutic compounds require testing for safety in animals before 
moving into human studies. The NIA maintains a contract for funding 
investigators or small companies who have potentially interesting 
candidate drugs but lack the means to begin the formal drug testing 
process to conduct animal studies to evaluate drugs for toxicity. If 
the toxicology screening is successful, the data generated can be used 
to file a request to the Food and Drug Administration (FDA) for 
approval to carry out initial tests for safety and efficacy in humans 
(Phase I trials).
    Mechanisms have also been developed to facilitate human testing as 
illustrated by two recent program announcements issued by the NIA. The 
Alzheimer's Disease Pilot Clinical Trials Announcement supports smaller 
pilot clinical drug trials to evaluate dose, duration, recruitment 
strategies, and other related issues. The Alzheimer's Disease Clinical 
Trial Planning Grant supports planning for the development of larger 
multi-site studies once pilot data are available. Multi-site studies 
can be funded through regular research grants or through the clinical 
trials consortium supported by the NIA known as the Alzheimer's Disease 
Cooperative Study (ADCS).
    The ADCS was established to support clinical trials on compounds 
which large pharmaceutical companies generally would not test. This 
category of compounds includes drugs which are off patent, or were 
patented and marketed for another use (but might be useful for 
treatment of Alzheimer's disease), or novel compounds from individual 
investigators or from small companies without adequate resources to 
underwrite clinical trials. The types of drugs that could potentially 
ameliorate symptoms and modify the disease process are varied but 
include, for example, anti-oxidants, anti-inflammatories, and compounds 
affecting estrogenic, neurotrophic, and neurotransmitter processes. The 
ADCS has stimulated numerous AD clinical trials, addressing treatments 
for both cognitive and behavioral symptoms. As a mechanism for 
translation of preclinical drug discovery results into clinical trials, 
the ADCS has, for example, done a Phase I safety study of a compound 
that stimulates the production of neurotrophins in the brain, which NIA 
supported through a grant awarded through the Small Business Innovative 
Research program and through preclinical toxicity testing supported 
through an NIA contract. The ADCS also conducts Phase II and III 
clinical trials (both treatment and prevention) of other compounds such 
as vitamin E, steroidal and non-steroidal anti-inflammatory drugs, 
estrogen, and melatonin for alleviating sleep disturbances. The ADCS 
has expanded the selection of drugs to go into clinical trials by 
calling on all neuroscience investigators supported by the NIA to 
identify drugs that may be tested in future ADCS clinical trials.
  alleviating caregiver burden and identifying patient care strategies
    Perhaps one of the greatest costs of Alzheimer's disease is the 
physical and emotional toll it takes on family, friends, and other 
caregivers. According to a recent study that analyzed data obtained 
through the 1996 National Caregiver Survey, dementia caregivers spend 
significantly more time on caregiving tasks than do people caring for 
those with other types of illnesses and experience greater difficulties 
in terms of employment complications, mental and physical health 
problems, and caregiver strain than do people engaged in other types of 
caregiving activities.\5\ While research on treating the root causes of 
AD is progressing rapidly, there is clearly a critical need to develop 
more effective behavioral and pharmacologic strategies to treat and 
manage problem symptoms in people who have AD and to alleviate 
caregiver burden. In response to this need, the NIH has made 
identifying patient care strategies and alleviating caregiver burden 
major goals of the NIH Alzheimer's Prevention Initiative.
---------------------------------------------------------------------------
    \5\ Ory, M.G., Hoffman, R.R., Yee, J.L., Tennstedt, S., Schulz, R. 
Prevalence and Impact of Caregiving: A Detailed Comparison Between 
Dementia and NonDementia Caregivers, The Gerontologist, 39(2), 177-185, 
1999.
---------------------------------------------------------------------------
    As part of the AD Prevention Initiative, the NIA, in collaboration 
with the National Institute of Nursing Research, is supporting the 
Resources for Enhancing Alzheimer's Caregiver Health (REACH) 
initiative. This five-year, six-site intervention trial is testing the 
effectiveness of different culturally sensitive home and community-
based interventions for families providing care to loved ones with mild 
and moderate dementia. These interventions include psychoeducational 
support groups, behavioral skills training programs, family-based 
interventions, environmental modifications, and computer-based 
information and communication services. Over 1,000 families are 
enrolled in the REACH study and approximately fifty percent are 
ethnically diverse (African-American or Hispanic). Recruitment for the 
first five sites was completed in 1999 and six-month outcome data will 
be available later this year.
    In addition to the REACH initiative, NIA is also supporting 
research on special care units (SCUs), which are separate sections of 
nursing homes for residents with dementia. The idea behind SCUs is that 
people with dementia might benefit from specially designed programs or 
environments that differ from those in the traditional nursing home 
setting. The NIA has established a ten-site initiative that is 
examining the nature and effectiveness of SCU care in institutional 
settings, using cutting edge research methods. Best practices and 
effective interventions derived from the SCU and REACH initiatives, as 
well as other caregiving research activities, will be disseminated to 
the public through the NIA-supported Alzheimer's Disease Education and 
Referral Center, in collaboration with other federal, state, and local 
agencies involved in caregiving initiatives and the network of 
Alzheimer's Association chapters in communities across the nation.
    The pace of scientific discovery in the area of Alzheimer's disease 
research, together with the energy generated by the Alzheimer's Disease 
Prevention Initiative, are grounds for excitement and optimism. The NIA 
recognizes that only through continued research will we thwart the 
inconceivable demands that unchecked growth of the population afflicted 
with AD would place on individuals, families, and society. Once again, 
thank you for your attention. I am happy to answer any questions you 
may have at this time. 













STATEMENT OF DR. STEVEN DeKOSKY, DIRECTOR, ALZHEIMER'S 
            DISEASE RESEARCH CENTER, UNIVERSITY OF 
            PITTSBURGH MEDICAL CENTER
    Senator Specter. We will turn now to Dr. Steven T. DeKosky, 
a neurologist, Director of the National Aging Institute's 
funded Alzheimer's Disease Research Center, and director of the 
Division of Geriatrics and Neuropsychiatry at the University of 
Pittsburgh.
    He chairs the National Medical and Scientific Advisory 
Council for the board of directors of the Alzheimer's 
Association. He also chairs the professional advisory board of 
the Greater Pittsburgh Chapter of the Alzheimer's Association, 
an M.D. from the University of Florida College of Medicine, an 
A.B. from Bucknell, and his number one credential is that he is 
the father of Allie DeKosky on my staff.
    Thank you for joining us, Dr. DeKosky. We look forward to 
your testimony.
    Dr. DeKosky. Thank you, Senator. Thank you for maintaining 
full employment in my household. It is a pleasure to be back 
before this committee. I was here 2 years ago to testify. I 
told you at that time that I was hopeful that we were getting 
answers that were going to be helpful in beating back 
Alzheimer's disease, hopefully in time for stopping what we see 
as a clear problem to come in the next several decades.
    Based on what has occurred over the past 2 years, I am much 
more confident that we will get answers to how to slow down or 
stop this disorder. You have reviewed a number of the issues 
that I was going to present in my formal testimony. You have a 
copy of it, so I do not wish to go through it again other than 
to make a couple of points about issues that you covered with 
Dr. Hodes, and also a couple which I think may be useful for 
the committee's deliberation.
    We have developed a number of animal models which the 
scientists, of course, all love, and that we said we thought 
would be highly effective in letting us explain what happens as 
far as trying to stop the disease. Indeed, they have been very 
useful. The vaccination or immunization with beta amyloid of 
mice that shows what many people thought could not be done at 
all, that you could not only stop the lesions from forming in 
these mice but also actually have them regress, is clear 
evidence. And the phase one trials, the first trials for safety 
in humans using that immunization technique actually are 
beginning now at three different institutions around the 
country.
    The chemicals or drugs that will suppress or stop the 
secretases, the biochemical scissors that cut this molecule in 
the wrong place and let amyloid form in the brain, are also 
about to enter phase one trials at several places around the 
country. And therefore although these are only safety trials, 
and that is first with respect to any of the drugs that we 
would use, it is pretty clear that we are at a point where even 
2 years ago we thought was speculative.
    The difference I think in why we would ask for additional 
funding now actually changes a bit. The kinds of studies that 
we will do for Alzheimer's disease and the reason that you are 
hearing about mild cognitive impairment or MCI, which is what 
we would describe as a recent memory function change in the 
absence of other changes of cognition, is because people who 
have that particular memory problem move to Alzheimer's disease 
at a rate--the number of people who have it per year--which is 
much higher than the rate of the normal elderly.
    Somewhere between 12 and 15 percent of people will develop 
this disorder--if you identify it, they will develop 
Alzheimer's disease subsequently. What that means from the 
standpoint of how fast we can do studies, how quickly we can 
determine whether a medication works in slowing that 
progression down, represents an economic advantage and of 
course an immense advantage to our patients.
    When we do studies, and I will use the ginkgo biloba study, 
which is the National Center for Complementary and Alternative 
Medicine plus NIA collaborative study, I am directing that 
study. That study will involve 3,000 normal elderly people who 
we will follow for 5\1/2\ years, to see whether ginkgo biloba 
will suppress the transition of people into either MCI or into 
Alzheimer's disease. That will take us 5\1/2\ years to get a 
yes or no, unless at 3 years when we do an interval analysis 
there is so clearly an effect of the ginkgo that we would stop 
the trial.
    Now, the citizens of the United States pay approximately 
$100 million for ginkgo-related products. The Government wanted 
to know, is this helpful, and there are a number of scientific 
reasons why ginkgo itself might be helpful, but that study will 
take good volunteer, altruistic citizens of the United States 
who will agree to take either a placebo or this pill for 5\1/2\ 
years. They are all over 75, there are going to be difficulties 
getting them all into the clinic. These studies are going to 
take us time.
    If we string them together 5 years at a time, based on our 
current restrictions of budget, by the time we string together 
two or three studies per year with respect to trying to slow 
the advent of Alzheimer's disease, we will already be into the 
middle of what is a huge demographic jump in the population at 
risk.

                           PREPARED STATEMENT

    Our data suggests that if you take any one of those bars of 
millions and take 50 percent of it, those are the people, 
because this is the group at 85 and above, who will have 
Alzheimer's disease, and if you look at that target, which is 
ours for 2020 and 2040, those are the people that we have to be 
ready to address.
    Senator Specter. Thank you very much, Dr. DeKosky.
    [The statement follows:]
                Prepared Statement of Steven T. DeKosky
    Chairman Specter, Senator Harkin, Members of the Committee. It is a 
pleasure to be back. It was only two years ago that I came before you 
for the first time. I was hopeful then. I am confident now that we are 
getting the important answers we must have to effectively treat 
Alzheimer's disease.
    We know a lot more than we did two years ago about the basic 
mechanisms of the disease and potential methods to treat or delay or 
prevent it. We have great momentum and synergy between the scientific 
and medical communities, which we must continue to support.
  --We have a vaccine that appears to stop amyloid deposition in a 
        mouse model of Alzheimer's disease, and safety trials of this 
        vaccine in humans are underway.
  --We have identified one of the two enzymes which initiate the 
        formation of the characteristic plaques of Alzheimer's disease 
        and are preparing to test inhibitors of this enzyme.
  --We now have several animal models to model different aspects of 
        Alzheimer's, including new ones that allow us to study the 
        neurofibrillary tangles that are the other major hallmark of 
        the disease.
  --We have discovered that the brain has its own system for generating 
        new neurons, leading to a novel potential therapy for 
        Alzheimer's as well as other brain diseases.
  --We have identified ``mild cognitive impairment''--a defect in 
        recent memory function, which is not yet Alzheimer's disease 
        but has an increased probability of developing into Alzheimer's 
        disease--a prime target for prevention.
    We must maintain the current level of investment in Alzheimer 
research just to continue the basic science that will complete our 
understanding of the disease. But that will not be enough. Because we 
are in a race against time.
    An estimated 14 million babyboomers are living with a sentence of 
Alzheimer's disease today. They will begin to turn 65 in 2010 and will 
enter the age of highest risk for AD about 2020. But we do not have 
that much time to find a way to prevent Alzheimer's disease. We know 
now that the disease process starts at least 10 years before these 
symptoms of the disease appear. Among those with mild cognitive 
impairment (MCI), 12 percent to 15 percent will convert to Alzheimer's 
disease each year. Within 5 years, half of those who now have MCI will 
actually develop full Alzheimer's disease. By that time, so much 
irreversible change in brain will have occurred that we will probably 
be able to do little about the further progress of the disease.
    This means that our window of time to prevent Alzheimer's is very 
short. We have to find answers within the next 10 years, before the 
babyboomers start turning 65 and enter the age of risk. That is why we 
need an additional $100 million this year, just for Alzheimer research.
    If Congress sticks with its commitment to double funding at the 
National Institutes of Health, and approves the $2.7 billion increase 
that you, Senators Specter and Harkin, are seeking this year, then we 
will have the money we need.

             THE ALZHEIMER'S DISEASE PREVENTION INITIATIVE
    Thanks to your additional investment in Alzheimer research over the 
past two years, the NIH--under the leadership of Dr. Hodes and the 
National Institute on Aging--has initiated the Alzheimer's Disease 
Prevention Initiative. Now, at least four large scale prevention trials 
are underway. They are testing various promising compounds anti-
inflammatory drugs, vitamin E, a current Alzheimer treatment drug, 
Ginkgo biloba, and estrogen to find out whether they can actually 
prevent or delay disease in people with mild cognitive impairment, or 
in those who have a family history of Alzheimer's but do not yet have 
any cognitive impairment.
    These trials are expensive. They can cost as much as $15-25 million 
each. They take time--at least 4 to 5 years--to find out if the 
intervention makes a difference. And findings need to be replicated by 
at least one additional study before we can implement them in the 
population at risk.
    If we spread out the money and do these studies one at a time, we 
will not find the answers in time. We must make the up-front investment 
in simultaneous trials now.

              A MINORITY INITIATIVE ON ALZHEIMER'S DISEASE
    Alzheimer's disease presents itself differently in particular 
ethnic and cultural populations. There are differences in risk factors, 
prevalence, family and community response; and the higher prevalence of 
diabetes and hypertension in some of these populations complicates 
evaluation and treatment. The Alzheimer's Disease Centers funded by the 
National Institute on Aging have opened satellite clinics to recruit a 
more diverse group of patients for our current research. But we need to 
do separate large-scale studies in minority populations to understand 
the impact of the disease and to discover novel, effective 
interventions.
    One of the most promising areas for new research is the 
relationship between vascular disease and dementia. Vascular disease is 
the most common comorbidity in Alzheimer's. There is intriguing 
evidence that vascular factors may influence the clinical expression of 
Alzheimer's, and that hypertension may increase the risk of dementia. 
We need to pursue that evidence, but this too will take large-scale 
clinical and pathological studies in community-based populations, for 
which we do not now have the resources.
    There is no area of scientific inquiry that holds more excitement 
or promise than the field of neuroscience, and Alzheimer research in 
particular. And there is no field that promises a bigger return on your 
investment. But we must act now. Time is running out.
    On behalf of the entire scientific community, and the patients for 
whom we are trying to find answers, thank you for your continued 
leadership and commitment.

    Senator Specter. Before going to questions, I am going to 
ask our other three panelists to join us at this time for their 
opening statements, and we will question them. Ms. Maureen 
Reagan, Mr. Frank Carlino, and Ms. Orien Reid. Would you join 
us, please.
STATEMENT OF MAUREEN REAGAN, MEMBER, ALZHEIMER'S 
            ASSOCIATION BOARD
    Senator Specter. We will begin with Ms. Reagan. Since 1999 
she has served as a member of the board of the Alzheimer's 
Association, a well-known political analyst and radio and TV 
talk show host, an accomplished author. In her book ``First 
Father/First Daughter'' memoir, she outlined never-before-
published anecdotes about her father, President Reagan. She has 
had several posts with the Republican Women, Republican 
National Committee, including cochair and special consultant to 
the chairperson for women's campaign activities. She also 
chaired a 36-member United States delegation to the 1985 World 
Conference of the United Nations Decade for Women. It is worth 
noting that in 1983 President Reagan signed a proclamation 
proclaiming the month of November 1983 as National Alzheimer's 
Disease Month.
    Ms. Reagan, we thank you for joining us. We look forward to 
your testimony. And this may begin a little unusually, but I 
know this is a question on everybody's mind. How is President 
Reagan?
    Ms. Reagan. Well, thank you, Senator. He is doing very 
well, but the disease gets worse, and that is about the best 
that I can say about it. I know that there is great concern on 
your part and many people's part when they ask that question, 
but I think there is also a little bit of glimmer of hope that 
perhaps we have been spared some of the ravages of this 
disease, but it is an equal opportunity disease, and it does 
not make special arrangements for former presidents or first 
ladies.
    Senator Specter. Thank you for that comment and the 
insights into how he is feeling. Now we look forward to your 
testimony.
    Ms. Reagan. Well, thank you. As I said, Alzheimer's disease 
does not make special arrangements. We have over 500 family 
members here today on the Hill who are very anxious to tell 
their individual stories, and I speak for them as well as for 
my family. This disease is a thief that sneaks into the brain 
and robs a family of everything that is dear as it takes the 
loved one.
    I am very grateful for Nancy Reagan. She is a model for 
caregivers throughout the country, and with the help of our 
good friend and nurse extraordinaire Diane, they make my 
father's days as stimulating and as fun as is possible to do.
    It is very hard work for caregivers. I have talked with 
hundreds of them as I travel around the country. The emotional 
toll of losing a loved one and the 24 hours a day that it takes 
to care for them is really quite devastating when you realize 
that most caregivers are older themselves, and they have their 
own health problems, which are many times left uncared for 
because of what they are doing for their Alzheimer's patients. 
And that is why it is very important, in addition to research, 
that we look at ways to provide more support for caregivers 
with the caregiver tax credit and with grants to states and 
communities for respite care and day care that can help the 
patient as well as the caregiver.
    As you said, in 1983, my father offered his proclamation, 
and he did it because this is a relatively unknown disease. It 
has stricken millions of people, and he felt it was time to pay 
attention to that. But even more important, in 1994, when he 
wrote his letter to the American people, told them that he had 
this disease and that he knew what was coming, he made it all 
right to talk about it.
    He brought it out into the open, and he caused light to 
shine in the lives of families who had dealt quietly and very 
much alone, and between his letter and the fact that the 
Alzheimer's Association over the last 20 years has worked so 
hard to bring attention to this disease, I think he has always 
been my hero, but never more so than when he did that.
    If he were sitting here today, Mr. Chairman, I know that my 
father would commend you and the members of this subcommittee 
for going beyond talk and increasing substantially the 
investment in research. Because of that investment, scientists 
are able to unlock the basic mechanisms of Alzheimer's disease 
and to offer hope to generations in the future. I encourage you 
to continue this support. I hope that our arguments today will 
benefit you as you go forward to talk to the rest of your 
colleagues because even if we were to come up with a way to end 
this disease today, there would still be four million--or to 
prevent it, there would still be over four million Americans 
like my father who would still need care. So we need to examine 
both sides, not only how we prevent the disease but how we deal 
with those people who are suffering.

                           PREPARED STATEMENT

    So for my father and for Nancy and for all the individuals 
and caregivers across America who are praying for help, I plead 
with you to redouble our efforts. We must be the last 
generation of American families to deal without hope. Thank 
you, Senator.
    Senator Specter. Thank you very much, Ms. Reagan. We 
obviously wish your father the very, very best.
    Ms. Reagan. Thank you.
    [The statement follows:]
                  Prepared Statement of Maureen Reagan
    Mr. Chairman and members of the Subcommittee: My name is Maureen 
Reagan and I am here to speak for my family and for millions of 
families who are struggling with Alzheimer's disease.
    The first question on your mind is, ``How's my dad doing?'' I am 
asked that question wherever I go. I suspect out of a sincere concern 
for my father, but also, I think, out of some heartfelt hope that maybe 
he and Nancy are being spared in some small way from the ravages of 
this terrible disease.
    Well, I have to report to you that Alzheimer's disease doesn't make 
special arrangements for President's or first ladies or anyone else for 
that matter. When it takes hold it follows its own course of 
destruction, frequently ravaging not only its direct victim, but also 
the caregivers and loved ones along with it.
    This disease is a thief that sneaks into the brain and robs its 
victims of so much of what is precious about life our memories and our 
experiences, ultimately life itself.
    I thank God for Nancy and the wonderful care she gives my dad. And, 
I thank God again for sending Diane, a nurse-extraordinaire. They are 
quite a team and he couldn't be better cared for. They, like millions 
of caregivers, make sure his days are as stimulating and fun as 
possible.
    But, it is hard work for caregivers. I've talked with hundreds of 
them as I travel around the country. The emotional toll of losing a 
loved one to this disease is wrenching. And, most caregivers are 
themselves older and, therefore, have their own physical limitations 
that are compounded by the enormous stresses of caregiving. We are 
fortunate in my family that we can afford help. Without it, this 
disease would be truly overwhelming. But, many families, for financial 
and other reasons, attempt to do it alone, or help simply isn't 
available. That's why you must enact some relief for caregivers this 
year.
    My father has always been viewed as a person with vision; someone 
who has the uncanny ability to see, in an unfiltered way, where we as a 
nation are and where we ought to be. More than sixteen years ago on 
September 30, 1983 he issued a Presidential proclamation that for the 
first time drew national attention to Alzheimer's disease. He was moved 
to do this, in large part, because this relatively unknown disease had 
stricken millions of families; yet most Americans had never heard of 
it. In that proclamation he wrote that, ``The emotional, financial and 
social consequences of Alzheimer's disease are so devastating that it 
deserves special attention.''
    And then in 1994 when the disease found its way into his brain, he 
had the courage to issue another kind of proclamation in the form of a 
very personal letter to the American people. My father has always been 
my hero, but never more than when he took that courageous stand, 
thereby drawing attention to, and making it alright to talk about, this 
awful disease. But talk isn't enough. We must do something about it.
    If he were sitting here today, Mr. Chairman, I know that my father 
would want to commend you and this subcommittee for going beyond talk 
and increasing substantially the investment in research. Because of 
that investment, scientists have been able to unlock the basic 
mechanisms of Alzheimer's disease, offering hope to generations in the 
future. I encourage you to continue that support for research and to 
add to it support for caregivers. Because even if we were to come up 
with a way to prevent this disease tomorrow, more than 4 million 
Americans, like my dad, will still be in need of care.
    So, for my father and Nancy and all the individuals and caregivers 
across America who are praying for help, I plead with you to re-double 
your efforts this year. We need you to increase the research funding on 
Alzheimer's by $100 million. We need you to fund caregiver support 
programs. And, we need your courage and steadfastness, not only this 
year, but in years to come to help bring this disease to its knees. We 
must be the last generation of American families to live without hope! 
And with your help we will be.

    Senator Specter. We will do our best, as we said before, to 
keep the funding coming and to try to work for the future. 
There are many people who want to come in. If you come to the 
far wall on this side, you are welcome to come in, if you move 
around and those on this side can move farther up here. You can 
even take some of the chairs. We will not have all those chairs 
filled. Be senators for a morning. Come on up. We want 
everybody who is in the hallway to gain access to the room. We 
have been joined by our distinguished Ranking Member, Senator 
Harkin. Tom.

                Opening Statement of Senator Tom Harkin

    Senator Harkin. Thank you, Mr. Chairman. I apologize for 
being late. We always have 10,000 things to do around here, but 
I did want to be here because of my long-time interest in this 
issue and because of the need to continue our efforts together.
    I just said to our chairman when I walked in, I said I 
heard a lot of clapping when I came around that corner down 
there, and I wanted to know what that was all about.
    Senator Specter. I told him that I mentioned his name.
    Senator Harkin. So I learned that my friend and 
distinguished chairman had said that we are going to continue a 
very strong bipartisan effort to get a doubling in for the 
National Institutes of Health. I just wanted to let you all 
know that I am in lockstep with him on this, and we will do 
everything we can to ensure that that happens and to make sure 
that we keep up the funding.
    I just ask that my statement be made a part of the record. 
I, too, want to join in wishing your father the best. You know, 
it really, because of who he is and because of his great life 
and the leadership he gave to this country, it really has 
brought home that Alzheimer's can hit anyone. It is not just 
someone maybe that did not take care of themselves. Your father 
was always the picture of health, I mean always the picture of 
health. And so I think it just brings home that no one is 
immune, no one, not anyone is above it, and that we really have 
to focus on this.

                           PREPARED STATEMENT

    I just would just say, Mr. Chairman, again along with you, 
I thank you for your leadership in this area. There are great 
breakthroughs being made. I am convinced, as I have watched the 
progress in areas like stem cell research, that I really 
believe that in a very short period of time we are going to be 
able to have interventions that will put off the onset of 
Alzheimer's. If we could just put it off for 5 years, they 
would tell me we would save almost $50 billion a year, just by 
putting it off for 5 years, so hopefully within the next few 
years we will have those interventions, and the next step, of 
course, is reversing it and finding a cure. To that end, I am 
sure we are all committed, and again I thank you all for being 
here. Mr. Chairman, again thank you for your leadership.
    Senator Specter. Thank you very much, Senator Harkin. Your 
full statement will be made a part of the record.
    [The statement follows:]
                Prepared Statement of Senator Tom Harkin
    Mr. Chairman, I want to thank you for having this hearing today and 
thank our distinguished panel for sharing their testimony with us. I 
also want to welcome the many volunteers with the Alzheimer's 
Association who have come to Capitol Hill today to advocate for more 
funds for Alzheimer's research and care giver support--and, in 
particular, I want to welcome the delegation from Iowa. I know you have 
your hands more than full, so your willingness to travel here is even 
more admirable. I want you to know, you are making a difference.
    I have had the privilege of visiting with and listening to Iowa 
families struggling with Alzheimer's and the high costs of health care. 
This disease takes a tremendous and terrible toll on families--it also 
takes a tremendous and terrible toll on family budgets.
    I believe we can invest smarter to help ease the burden on families 
and save taxpayers at the same time. That's why Senator Specter and I 
are fighting so hard to increase our national investment in medical 
research. Nearly $100 billion a year is lost to the economy each year 
because of Alzheimer's. But if we were to just delay the onset of 
Alzheimer's's by five years, we could save as much as $50 billion a 
year.
    Today, about 15 percent of the Pentagon's budget goes to research & 
development. But less than 3 percent of our health dollars are invested 
in research. Pentagon research has paid off. It's time to invest in a 
smart bomb to wipe Alzheimer's off the face of the earth. By investing 
more in research we can save money and save lives. And in the meantime, 
we also need to do more to help care givers cope with the tremendous 
stresses and costs of Alzheimers.
    Thank you, Mr. Chairman and I look forward to hearing from our 
witnesses.
STATEMENT OF ORIEN REID, CHAIRMAN, ALZHEIMER'S 
            ASSOCIATION BOARD
    Senator Specter. We now turn to Miss Orien Reid, elected as 
chairman of the national board of directors of the Alzheimer's 
Association November of last year. She was a primary caregiver 
for her mother who died from Alzheimer's disease in 1992. She 
spent 26 years as a television and radio consumer reporter in 
Philadelphia, where I got to know Orien on a personal basis. 
Began at KYW news radio and most recently at WCAU-TV. Currently 
owns her own media consulting business. A master's from Atlanta 
University School of Social Work and her BA from Clark College. 
Thank you for joining us, Ms. Reid.
    There are still some more chairs up here for people who 
want to sit. We welcome you five ladies to the Senate panel.
    Ms. Reid, the floor is yours.
    Ms. Reid. Well, thank you, Senator Specter and Senator 
Harkin. A couple of years ago, as you mentioned, I came here as 
a caregiver to speak for my mother and my grandmother, my aunt, 
and my uncle, all of whom had Alzheimer's disease, and also to 
speak for my children, who are just simply terrified that this 
killer has just not let our family go yet, but today I am 
speaking as the chair of the Alzheimer's Association.
    I speak for our 200 chapters, for the 4 million people who 
have Alzheimer's disease now, and their families, and for the 
14 million baby boomers, of whom I am a part, who are going to 
get this disease if we do not do something very soon.
    We are here to thank you today for your commitment and your 
enormous effort in helping us to fund research to end this 
disease, and I also want to submit a copy of the Association's 
national public policy program to conquer Alzheimer's disease. 
Today you have 500 people who are here who are going to be 
taking this document personally to their Senators and 
Representatives to tell them about our program to end 
Alzheimer's disease.
    Our first priority is research. Your proposal is just 
outstanding for $2.7 billion to increase the NIH's budget so 
that we can get--we believe we need $100 million to fight 
Alzheimer's disease. I am not a scientist, and I would not 
presume to present even more evidence than has been presented 
by Dr. Hodes and Dr. DeKosky, but I can add for you a very 
personal note.
    For each of us in this room and for anyone who has ever 
been touched by Alzheimer's disease, Senators, we are simply in 
a race against time. Would you believe that today I am only 15 
years younger than my mother was when she received the sentence 
for Alzheimer's disease, and the researchers say that if I am 
going to get this disease when I reach her age, the molecular 
mischief has already begun in my brain. I just do not have any 
time to spare.
    In the 8 years that I have been involved with the 
Alzheimer's Association, I have heard scientists change their 
message from one of cautious optimism to, at best, to outright 
certainty that we can end this disease, but only if we have 
enough resources to do it.
    The agenda for research is very clear, as you have already 
heard from the experts. We need the additional $100 million to 
launch the kinds of prevention trials that Dr. DeKosky talked 
about. We also need to finally start a minority initiative on 
Alzheimer's disease. We need to make sure that we are 
developing the kinds of diagnostic tools and the kinds of 
interventions that work for everyone and not just for one 
particular population.
    We know we do not have to persuade you because you are 
already on our side, and you understand this, but our job is to 
convince your colleagues. We will be talking to some of the 
members of the other committees who are responsible for 
Medicaid and Medicare funding, and we will show them how the 
future of these two programs directly depends on our success to 
end Alzheimer's disease.
    Medicare spends 70 percent on average more for health care 
for a beneficiary with Alzheimer's. Medicaid spends 65 percent 
more, and 22 percent of the dual eligibles, those on Medicaid 
and Medicare, are folks with Alzheimer's disease. So our 
message to your colleagues is very simple. There is no way that 
you can save Medicare and Medicaid unless we bring Alzheimer's 
disease under control, and we can only do that through 
research, and for baby boomers like me, and like you, Senators, 
there is an increased sense of urgency.
    Briefly, there are two other important issues that we feel 
are so very important. We urge you to appropriate $25 million 
this year for Alzheimer's demonstration grants. I have already 
handed in my written testimony. It describes how effective this 
has been for 15 communities where actually they have changed 
the way they can deliver services to people with Alzheimer's 
disease.
    We are also asking for support for the family caregiver 
support program, and we are asking for funding this year.

                           PREPARED STATEMENT

    Mr. Chairman, I know that you have lots of priorities that 
you have to balance, and we appreciate that, but when we look 
to the future, we must find a way to end this disease, so I 
thank you for all of your support, for all of your efforts. And 
for all of the people in the Association and for my children 
and my grandchildren, I thank you.
    Senator Specter. Thank you very much. Thank you very much 
for those very touching and profound remarks.
    [The statement follows:]
                    Prepared Statement of Orien Reid
    Thank you, Senator Specter and Senator Harkin for holding this 
hearing and inviting me today. Several years ago, I came here as a 
caregiver to speak for my mother, my aunt, my uncle, and my grandmother 
all of whom had Alzheimer's disease. And to speak for my children, who 
are terrified that this killer is not finished with our family yet.
    Today, I am here as Chair of the Board of Directors of the national 
Alzheimer's Association. I speak for our 200 chapters, the 4 million 
people who have the disease now and their families, and the 14 million 
babyboomers who will get Alzheimer's if we do not stop it soon.
    I would like to present to you the Association's National Public 
Policy Program to Conquer Alzheimer's Disease. Today, 500 Alzheimer 
advocates from across the country will deliver this National Program 
personally to their own Senators and Representatives.
    We are here to thank you for your constant leadership on issues 
that matter to the Alzheimer community, and to tell you that we are 
behind you in your continued efforts to increase funding for Alzheimer 
research and services.
    As you know, the Alzheimer's Association is the only national 
voluntary agency dedicated solely to this terrible disease. Our mission 
is to create a World Without Alzheimer's Disease while we support the 
families who must deal with it today. We know that you share those 
goals and, with your help, we will accomplish them.
    Our National Program calls on Congress to act in 3 areas: research, 
Medicare, and long term care. We know that some of these issues fall in 
the jurisdiction of other Committees. We are here to talk to you about 
those issues that are before this Subcommittee.
    Our first priority is adequate funding for Alzheimer research. Your 
proposal for a $2.7 billion increase in overall funding at NIH this 
year the next step in your efforts to double funding within 5 years is 
absolutely essential if we are to find the additional $100 million that 
we need for Alzheimer research.
    I am not a scientist and would not presume to add to the persuasive 
scientific arguments that the researchers are presenting at this 
hearing. But I can make a very personal plea, for each of us in this 
room and for every family that has been touched by Alzheimer's disease. 
We are all in a race against time. Right now, I am only 15 years 
younger than my mother was when she received her sentence of 
Alzheimer's disease.
    The researchers say that if I am going to get the disease by the 
time I am the age she was, the ``molecular mischief'' in my brain has 
probably already begun. I do not have any time to spare.
    In the 8 years I have been involved in the national Alzheimer's 
Association, researchers have changed their tune. They are no longer 
``cautiously optimistic.'' They are confident that we can master this 
disease--if we have the resources to do so. The agenda for research is 
clear, as you have already heard from the experts. The additional $100 
million will provide the resources for two urgent priorities.
  --First, for the Alzheimer Prevention Initiative to accelerate the 
        expensive large scale clinical trials that will prove which 
        treatments work to prevent the disease, and to develop the 
        techniques for early diagnosis to make sure that those 
        treatments get to the right people, in time to make a 
        difference.
  --Second, for a Minority Initiative on Alzheimer's Disease. By 2030, 
        25 percent of the aging population will be non-white. 
        Alzheimer's differs in these population groups, and a common 
        condition among minorities hypertension may increase the risk 
        of dementia. We must start the studies now to understand the 
        impact of the disease in diverse populations, to determine the 
        relationship between vascular disease and dementia, and to 
        discover effective interventions.
    For your colleagues on other Committees who are responsible for the 
future of Medicare and Medicaid, we will make the argument that the 
future of these programs will depend directly on our success in slowing 
the progress of Alzheimer's disease. We already know from the Health 
Care Financing Administration that Medicare spends 70 percent more on 
average, for a beneficiary with Alzheimer's disease. Now, a new study 
from Pennsylvania shows that Medicaid long term care costs 65 percent 
more for a beneficiary with Alzheimer's disease.
    There is no way to save Medicare and Medicaid if we do not bring 
Alzheimer's disease under control, and we can only do that through 
research.
    The second matter before your Committee is funding for Alzheimer 
services. Since 1992, you have funded small grants to states as little 
as $250,000 each--that are changing the way Alzheimer families receive 
the services they need. The projects focus on underserved ethnic and 
cultural minorities and rural communities. Let me give you a few 
examples of the innovations your investment has brought in the states 
that have been lucky enough to get the grants:
  --In Maine, dementia teams that are linked to university specialists 
        now go to the homes of people in isolated rural areas and 
        regularly consult with their family physicians.
  --Small towns in Georgia that cannot support a full time adult day 
        care center are now served by a mobile dementia day care 
        program.
  --Latino families in South Central Los Angeles now have a 
        comprehensive Alzheimer community services program, and the 
        initial seed money from the federal government has been totally 
        replaced with locally raised funds.
  --Oregon has trained all of the case managers in its long term care 
        system to understand the special needs of people with dementia 
        and, as a result, the entire system is more responsive to those 
        needs.
    Annual appropriations for this program has never exceeded $6 
million. That has been enough to fund only 15 projects, although more 
than 40 states applied for the money. This year, the Administration on 
Aging is seeking new competitive grant applications. We expect most 
states to submit proposals. We urge you to appropriate $25 million to 
allow these innovations to go forward in every state that submits a 
qualified proposal. As states and health care systems redefine their 
services to meet the needs of a growing aging population, this program 
will help assure that people with Alzheimer's disease do not fall 
through the cracks again.
    Finally, may I say just a word about the broader issue of caregiver 
support. I realize this is not the topic of today's hearing. But I want 
to make clear that the Association supports the proposals before 
Congress that would support all caregivers, whether they are dealing 
with Alzheimer's disease or another devastating illness or disability. 
A $3,000 tax credit and a $125 million appropriation for a family 
caregiver program--proposals that have strong bipartisan support--are 
important steps you can take now to shore up the families who are the 
invisible care system in our country.
    Mr. Chairman. We know there are competing priorities before this 
Subcommittee, and we understand the fiscal constraints under which you 
must try to balance those priorities. But as we look to the future, the 
case for a frontal assault on Alzheimer's disease is overwhelming. This 
hearing demonstrates your own concern about the looming crisis and your 
commitment to averting it. On behalf of everyone in the Alzheimer's 
Association, for every family dealing with Alzheimer's disease, and for 
our children and grandchildren, thank you.
STATEMENT OF FRANK CARLINO, ALZHEIMER'S PATIENT
    Senator Specter. We turn now to Mr. Frank Carlino, a 
resident of Cornwall, New York. In July of 1998, at the age of 
58, Mr. Carlino was diagnosed with early onset Alzheimer's 
disease.
    Prior to falling victim to Alzheimer's disease, he operated 
his own architectural consulting firm. Currently taking part in 
an early onset support group organized by the Mid Hudson 
Chapter of the Alzheimer's Association. Received his 
architectural degree from Pratt Institute in New York. Thank 
you for joining us, Mr. Carlino, to share with us your 
experiences.
    Mr. Carlino. Thank you very much, Senator Specter and 
Senator Harkin, for giving me the opportunity to be here and to 
represent my 4 million fellow Alzheimer's sufferers.
    You have my written testimony, so I would like to speak to 
you from my heart. Alzheimer's has taken a life, a pleasurable 
life. I have been married for 40 years to a most wonderful 
woman, my wife Elizabeth, who is the wind beneath my wings. I 
have 4 wonderful children and 13 grandchildren.
    We enjoyed a terrific life, and then the bottom fell out. I 
had my practice for close to 30 years, and I lost it because I 
was not able to think properly. Not knowing that I had early 
Alzheimer's, I was able to take a job with the consulting firm, 
the Archdiocese of New York, and I lost that because I could 
not perform. It was then that I found out that I had early 
Alzheimer's.
    In the meantime, between losing my business and so forth, I 
got into considerable debt, and my wife is now the principal 
breadwinner. Speaking through the eyes of someone with 
Alzheimer's, it is devastating, because I can no longer 
provide. To make matters worse, I get put in a Catch-22 
situation, Senators, where the Government tells me, well, you 
are 100 percent disabled, therefore you cannot work, you cannot 
earn any more than $200 a month, so sit on the couch and enjoy 
life, what is left of it.

                           PREPARED STATEMENT

    All this has been taken away. You asked the doctors before 
what you can do to justify the expenditure before your 
colleagues. Please, Senators, take them my message. My life is 
slipping away. They have the ability to save it. They are the 
life preserver. I am drowning. Save me, please. God bless you.
    [The statement follows:]
                  Prepared Statement of Frank Carlino
    Thank you very much Senator Specter and Senator Harkin for giving 
me the opportunity to testify. I am honored to be here.
    My name is Frank Carlino and I am from Cornwall, New York. I have 
been married to my wonderful wife, Elizabeth, for 40 years. We have 
been blessed with 4 terrific children and 13 amazing grandchildren.
    I was diagnosed with early onset Alzheimer's disease in July 1998. 
At the time, I was 58 years old. Although Alzheimer's disease primarily 
affects older people, an increasingly large number of early-onset 
patients are in their 40's and 50's.
    I am aware that on the outside, it does not appear that there is 
anything wrong with me. In fact, I may even look like someone you 
know--a friend or neighbor or even a colleague. But I have a disease 
that is slowly destroying my mind. I am here today to tell my story and 
to thank you for your steadfast leadership on Alzheimer issues.
    My story actually began almost a decade ago. In the early 1990's, I 
began to have trouble doing ordinary tasks and I started making 
mistakes at work. At the time, I had my own architectural firm. I 
employed 12 people full time but I was struggling because the economy 
was bad and the country was in a recession. As a result, there was very 
little work available in the community and I was worried that I would 
have to lay off some of my staff. I was under a tremendous amount of 
pressure and my mistakes became more frequent. I managed to come up 
with a variety of excuses for my poor performance--stress, anxiety 
about the future, concern for the welfare of my employees, etc. I 
figured that I was just going through a rough patch and that things 
would correct themselves over time.
    The recession ended, the economy turned around and my firm began to 
send out proposals and bid on jobs again. Although I would send out 25 
proposals a week and we were bidding on as many jobs as possible, we 
still weren't getting any work. It was only after I was diagnosed that 
I realized why almost all of our proposals were rejected. They were a 
mess! I had submitted poorly organized proposals and bids that were 
full of spelling errors and grammar mistakes.
    As my business continued to fail, I was approached by the 
Archdiocese of New York and offered a job as an architectural 
consultant, covering a 60 parish territory. I closed my practice and 
went to work for the Archdiocese. Although I was devastated by having 
to close my business, I was relieved to be getting out of that high-
pressure situation.
    At first, I was doing well in the new job but then I began having 
trouble. I missed appointments, couldn't finish assignments and began 
getting lost in communities that were familiar to me. My supervisor 
became aware of my missed appointments and poor performance and about 
18 months after I started, he called me into his office and suggested 
that I see a doctor about my problems. He told me that if I had a 
medical problem I could go on disability but that if I didn't get 
checked out, he would have to let me go because I couldn't handle the 
job.
    I saw my family doctor immediately who referred me to a 
neurologist. I had a complete medical work-up including an MRI, many 
blood tests and a memory test. Within 3-4 months the diagnosis was 
complete--early onset Alzheimer's disease.
    Overnight, my life was turned upside down. I lost my job and went 
on disability. I was declining very rapidly so my neurologist suggested 
that I begin taking Aricept. I noticed an almost immediate improvement 
after I began taking the medication. I could function again and 
complete tasks. I felt like I was starting to get my life back. I am 
still on Aricept and I honestly believe that it has slowed the 
progression of my disease. But I know it won't stop the inevitable.
    As an architect, I could do algebra and geometry in my head and 
calculate complicated dimensions for high rise buildings with ease. In 
high school, I got an almost perfect score on the New York state math 
exam. Today, I can't balance my checkbook. After high school, I spent 
three years in the Army in a Special Operations unit. Everything had to 
be committed to memory. I can't memorize five items on a shopping list 
now.
    Alzheimer's disease prematurely ended my career and destroyed my 
financial security. It will steal my memories and eventually it will 
rob me of my independence but I will not let it take my spirit. Instead 
of dwelling on what I have lost, I am focusing my attention on the 
activities I can still enjoy. I am a deacon in my church. I participate 
in a wonderful early-onset support group organized by the Alzheimer's 
Association Mid-Hudson Chapter. There are 5 of us in the support group 
and we have become great friends. The support group has also been a 
great resource for my wife. I still drive although I have an agreement 
with my doctor that I will not drive anywhere that is more than 25 
miles from my home. I keep maps of places I go on a regular basis, like 
the doctor's office or the hardware store, in my car. I am perhaps one 
of the few men in this room who will not hesitate to ask for 
directions! I am also in the process of converting a New York City 
transit bus into a motor home that my wife and I are planning to take 
on weekend camping trips. The project is nearly completed and it has 
given me a tremendous sense of satisfaction.
    While I am still able, I want to do whatever I can to speak out 
about Alzheimer's disease. I have traveled to Washington to meet with 
my Senators and Representatives and I am testifying here today to urge 
you to continue the investment in research so that we can spare my 
children and grandchildren and the children and grandchildren of other 
Alzheimer families from this devastating disease. We are in a race 
against time and we need your help!
    Thank you.

    Senator Specter. Mr. Carlino, your comments are obviously 
overwhelming, and we are very sorry to hear what has happened 
to you, and we know that your situation is representative as to 
what has happened to so many, many Americans, and people really 
around the world, and we hear you, and we are dedicated to 
doing everything we can through Federal assistance, to funding, 
to assist you.
    If the assistance can come in time for you and for Ms. 
Reid, who comments about being 15 years away from her mother's 
age, and of course you are there. When you talk about your 
losing your practice because you could not think properly, I 
would be interested and I think others would be, too, to know 
just what happened to you when you, as you put it, could not 
think properly.
    Mr. Carlino. Senator, when you have a business, it is 
probably the toughest way for somebody to analyze that you have 
Alzheimer's or that something is wrong because you have many 
people performing tasks for you. In other words, in the morning 
my secretary would run down my list of appointments. When I 
would misplace things or I would forget things, it did not 
register because there was somebody else to pick up for me.
    But sending out proposals, Senator, I was at a point 
where--when I graduated high school I had an IQ in excess of 
150, OK? I could do algebra, geometry in my head. When I was in 
the service I was a member of the special operations unit in S-
2 and had to commit a lot of information to memory. When it got 
to a point where I was sending out proposals, I used to be able 
to bring in one job for every three proposals or presentations 
that I went on. I was sending out proposals and was not getting 
short-listed on one out of 50.
    And if you take a look at them now, you can understand 
because when I put the proposals together I was forgetting to 
put in all the proper information.
    Senator Specter. Mr. Carlino, what are your doctors doing 
for you at the present time?
    Mr. Carlino. I am on Aricept, I am on Prozac, I am on 
BuSpar, all to help my mood. I undergo neurological testing 
once every 3 months, and I see my primary physician once every 
3 weeks.
    Senator Specter. Dr. DeKosky, a two-part question. What can 
be done for Mr. Carlino now and what can be done for Mr. 
Carlino with increasing the funding to $100 million more than 
the $466 million?
    Dr. DeKosky. For Mr. Carlino now, the only medication 
specifically approved for the treatment of Alzheimer's disease 
is Aricept. He is on that medication. There is one more 
medication for symptomatic treatment that will come onto the 
general market in either May or June. There probably is a third 
currently before the FDA which will, if it is approved, be 
generally available in the year 2001.
    Senator Specter. A third product?
    Dr. DeKosky. A third symptomatic treatment medication. The 
vitamin E trial that was one of the first trials that showed we 
could at least affect the course of the disease, which was 
completed 2 years ago, is another medication to try. But for 
people like Mr. Carlino who are as articulate as he is now and 
who show the face of Alzheimer's disease that people do not 
think about, people who are still quite normal and quite able 
to interact every day, the slow--the progression medication 
trials, the mild cognitive impairment trials are exactly 
targeted toward. They are the people who we are trying to have 
the disease stop in.
    We think that the same medications that work for slowing 
down, frankly, symptomatic Alzheimer's disease should work in 
mild cognitive impairment. We would probably have to test them 
separately, but there is no question that we would try them 
immediately and rapidly. But when I tell you about the 
imperative of time, and the fact that, for example, to conclude 
a mild cognitive impairment that starts today would probably 
take us a minimum of 3 years, we have a problem helping Mr. 
Carlino as quickly and as effectively as we would like to do.
    Now that science has been the success that it has, to say 
here are the medications that are safe enough and presumably 
effective enough to be put into trials, the medication to run 
those long and expensive trials would have to simply come out 
of the monies which have already been budgeted for the science 
and the other clinical trials.
    The major focus of this request for an increase is to build 
on the successes that we have had and start the clinical trials 
now, because ones that start today for mild impairment probably 
cannot be completed in less than 3 years, and the primary 
prevention trials would probably take a minimum of 5 years, and 
they cost $15 to $20 million each. If we string them out 5 
years at a time, we will be in the middle of that epidemic 
before we have answers.
    Senator Specter. Dr. DeKosky, sometimes the medicines are 
pretty well established even before FDA gives final approval. 
You say there are two in that category. Is it worth exploring? 
Let me ask you to do this. My red light is on. I have one more 
question before yielding to Senator Harkin. Would you talk to 
Mr. Carlino and see if either of those two--sometimes it is 
possible to shake loose some of that from the FDA.
    Dr. DeKosky. I will do that, certainly.
    Senator Specter. I know he has his own doctors, but I doubt 
that he has doctors with your pedigree. So if you would talk to 
him, I would appreciate it.
    Dr. DeKosky. I will do so.
    Senator Specter. The one other question I have before 
yielding to Senator Harkin is a similar question for Ms. Reid. 
She has given us a chronology of 15 years. What can be done for 
Ms. Reid?
    Dr. DeKosky. Well, Ms. Reid is--actually along with other 
baby boomers, and one of the best guarantees we have the 
research will be done is that many of the leading scientists 
now are boomers who are looking at that age of risk--is, these 
studies are directed toward these people. These studies, the 
primary prevention and the mild cognitive impairment trials are 
directed toward the group who is currently now between 50 and 
65. It is to know whether or not we can stop the progression in 
people over 65 that would let us know that either in their 50's 
or when they reach a significant age of risk, which is 65 to 
70, you could put people on safe and effective medications that 
would effectively delay the onset of the disease until after 
their normal life expectancy.
    So although we talk about and we would be happy to have a 
5-year delay, that would save about $50 billion a year, about 
50 percent of the current burden, if we had a 10-year delay, 
which based on some of what we know about reversibility in 
brain or slowing progression down in brain is achievable, we 
probably could eliminate up to 80 percent of the disorder. We 
will not catch everybody. There is no disease for which we have 
effective treatments where we could realistically expect to 
stop everybody, but we certainly could launch the equivalent--
for example, if it were vaccine or medications, that we do for 
pneumonia vaccinations or flu vaccinations and other sorts of 
highly successful and economically advantageous public health 
measures.
    Senator Specter. Senator Harkin.
    Senator Harkin. Thank you, Mr. Chairman. The question I had 
for--well, first of all, I know there are a number of Iowans 
who are here, and it is estimated over 68,000 Iowans are now 
suffering with Alzheimer's disease. You know, it affects us 
all. I just listened to your stories.
    My grade school teacher, Mary King--well, she was Mary 
Powers then, Mary King later--lived right across the street 
from me in a small town in Iowa, and until a year ago, a year 
ago she was just fine. And lived by herself, but right across 
the street lived my brother, who is disabled, and she was 
always kind of looking after my brother.
    I just visited Mary King last month--I am sorry, in 
January. And she has to be in an Alzheimer's unit of a nursing 
home, which is locked up so she does not wander off because she 
gets lost and does not know how to get back. And just to see 
how rapidly it happened, in 1 year. A year ago she was just--
you could not tell. So while I have thought about Alzheimer's 
as being a slow progression, I am wondering what happened 
there? How come sometimes it is so rapid like that, Dr. 
DeKosky? Is this just another form of Alzheimer's?
    Dr. DeKosky. Senator, my first question is how old is Ms. 
Powers?
    Senator Harkin. Well, Mary must be about 78 or 79 right 
now.
    Dr. DeKosky. Mr. Carlino's comments about the fact that 
there were people around to help him or that things happened so 
slowly that he did not notice it applies in many cases to 
people especially who are elderly who maintain themselves well. 
Two things happen.
    If you have lots of help, people think you are 
idiosyncratic or eccentric if you are very wealthy, and they 
take care of the things you forget. And if you do not have much 
help you actually usually fall earlier or if no one is watching 
you. So it may well be that she had symptoms and that as a 
highly intelligent and educated teacher, she had sufficient 
brain reserve, such as I think Mr. Carlino clearly 
demonstrates, and that when she exhausted that reserve, she 
became symptomatic relatively rapidly.
    I do want to make one more comment, although you were not 
here, Senator, for that testimony, it had to do with Senator 
Specter's question about the testing for ApoE4. The reason I 
asked you about her age was that although ApoE4, not unlike 
stem cell research, is teaching us tremendously useful things 
about the processes that happen in the brain in neurological 
disease, most of the risk of ApoE4 occurs in people who have 
onset before age 80. And that if we look at people over 80, 
especially this big group over 85, there is very little ApoE4 
effect in that group, and they are actually a major group that 
we are targeting.
    So although in the clinics the people who come in are 
younger and it makes it look as if the ApoE4 has a very strong 
effect in the whole population, in fact, it is applicable as a 
risk to our younger people below 70, and I would say below 75, 
but it is not a risk for this other large population who are 
over the age of 80. And that is one of the other reasons why it 
is a mixed blessing.
    People think that it will tell them the definitive yes-no 
if we test them. And so we either can engender a false sense of 
security since more than 50 percent of the people who get it do 
not have ApoE4 or we can make people worry. And we do not yet, 
Senator, have the effective treatments that if we screened the 
population for E4 positive people, we would say we are going to 
put you on this medication at this point in time. And I think 
that is why all the groups who have issued advisories have 
cautioned against examining asymptomatic people.
    Senator Harkin. Dr. DeKosky, I understand you have received 
a grant from the National Center for Complementary and 
Alternative Medicine to study the effect of ginkgo biloba on 
dementia. How far along are you in studying the effect of this 
supplement and could you also talk about vitamin B and what 
kind of promises are these type of therapies showing for the 
prevention or at least the alleviation of Alzheimer's disease?
    Dr. DeKosky. Thank you, Senator. The ginkgo biloba trial I 
believe will get underway with recruiting patients as subjects 
because these are normal people, probably in May or June, in 
four cities around the United States; in Pittsburgh, in 
Winston-Salem, South Carolina through Wake Forest, and 
Hagerstown through Johns Hopkins, and in Sacramento through the 
University of California-Davis. They are the centers of the 
cardiovascular health study, which is an add-on, saving us 
money. It is a structure that had been around for 10 years that 
we are now going to do this study over the top of.
    There are reasons that we think ginkgo biloba might be 
helpful in Alzheimer's disease beyond its 1,600-year history. 
It has antioxidant properties. It also thins the blood very 
slightly. But we have not proven that it works and we cannot 
until we try it. But it will take us 5\1/2\ years to complete 
that study because we are doing it in normal people over the 
age of 75, and on average only 1 percent to 2 percent, perhaps 
3 percent of normal people convert to Alzheimer's every year.
    So we not only need 3,000 people that we have to see every 
6 months, we have to see them for 5\1/2\ years before enough 
people convert to Alzheimer's who have either real drug on 
board or placebo and then test the statistical difference 
between the two groups. That is why we cannot do these studies 
strung end to end.
    Senator Harkin. My red light is on. Can I have one more, 
quick? I have a good softball here for you, Dr. DeKosky. The 
Senate and House are currently conferencing, and I am one of 
the conferees, on the Patient's Bill of Rights legislation as 
it is called. Both bills currently contain provisions to allow 
patients to access clinical trials by requiring insurance 
companies to pay the routine patient care costs associated with 
these trials. However, the Senate bill limits access to the 
trials to cancer patients only, while the House bill allows 
participation for patients with all diseases, including 
Alzheimer's.
    Dr. DeKosky, as a researcher, can you tell me if there is 
any scientific rationale for limiting reimbursement for the 
routine costs of clinical trials to cancer patients only?
    Dr. DeKosky. No, sir, I cannot.
    Senator Harkin. I told you it was a softball.
    Dr. DeKosky. I am sufficiently stunned by the logic of that 
that it took me a moment to answer. But, no, there is no 
reason. In fact, it would probably be a real synergy with the 
research community for all medical diseases.
    Senator Harkin. I wanted to make that point. With so many 
people here and with this bill now being conferenced, that--I 
wanted to make that point, that why limit it only to cancer 
patients? It should be open to all, and for clinical trials.
    The project you have ongoing with ginkgo biloba and things 
like that, you said it would take a long time. These kind of 
trials should be open to all people and not just limited. I 
just hope people understand that, and, what the heck, I mean, 
you are in the right place to see your Congressmen and Senators 
about that, so I urge you to make your interests in this known 
on that one specific thing. I will make it very clear to all of 
you again in the audience, that--as this Patient's Bill of 
Rights gets hammered out in conference, that to make it make 
clinical trials accessible to all and covered by the insurance 
companies and not just to cancer patients. So if you will do 
that for me, I would sure appreciate it. Thank you. I am sorry, 
Ms. Reagan?
    Ms. Reagan. Senator, you mentioned something about your 
friend in Iowa that, I thought it would be a nice time for us 
to mention something we do in the Alzheimer's Association. We 
have a safe return program which takes about a million dollars 
in the Department of Justice budget every year, but it is an 
identification bracelet that is registered with local police, 
just like Mr. Carlino has here, and this way if somebody does 
wander or gets lost, we can get them home. And we are very 
proud of that program, and we want to be sure everybody gets 
home safely.
    Senator Harkin. I have heard of that. Thank you. That is a 
good point. That is in the Justice Department? That is funded 
out of the Justice Department?
    Ms. Reagan. Yes.
    Senator Harkin. About a million a year, you think?
    Ms. Reagan. About a million, yes.
    Senator Harkin. We will have to keep our eyes on that one, 
too.
    Senator Specter. We shall. That comes through another 
subcommittee, but we will take a look at it.
    Senator Harkin. Yes, not ours.
    Senator Specter. We thank you all very much for coming. Dr. 
DeKosky, if you would supplement your testimony with a written 
response to the questions I asked Dr. Hodes, what do you think, 
how many of those 78 percent ought to be funded, what the cost 
would be, what you think a budget would be to do the job 
totally.
    Dr. DeKosky. Yes.
    Senator Specter. Appreciate that. And Ms. Reagan, we thank 
you very much.
    Ms. Reagan. Thank you, Senator.
    Senator Specter. I know that my colleagues all would ask 
that you send our best to your father when you see him again.
    Ms. Reagan. I certainly will.
    Senator Specter. Ms. Reid, we thank you for coming. Mr. 
Carlino, we got you another doctor today.
    Mr. Carlino. Thank you.
    Senator Specter. And to the extent that we can focus in on 
your condition as you are, we want to preserve you much beyond 
58, and we want to preserve that 150 IQ, a great rarity.
    Mr. Carlino. Thank you.

                         CONCLUSION OF HEARING

    Senator Specter. Thank you all very much for being here, 
that concludes our hearing. The subcommittee will stand in 
recess subject to the call of the Chair.
    [Whereupon, at 10:25 a.m., Tuesday, March 21, the hearing 
was concluded, and the subcommittee was recessed, to reconvene 
subject to the call of the Chair.]

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