"the worst public health problem of the next century,"3 and "the disease .... Figure 3 shows the results of a trial of lecithin and oral physostigmine in two patients ...
331
ALZHEIMER'S DISEASE: THE INTERSECTION OF DIAGNOSIS, RESEARCH, AND LONG-TERM CARE JAMES A. MORTIMER, Ph.D., KENNETH HEPBURN, Ph.D., and GABE J. MALETTA, Ph.D., M.D. Geriatric Research, Education and Clinical Center Veterans Administration Medical Center
Departments of Neurology and Psychiatry University of Minnesota Medical School
Minneapolis, Minnesota
Alzheimer's disease has received a great deal of public attention recently. It has been described in such terms as an "epidemic,"13 "the worst public health problem of the next century,"3 and "the disease of the century . . . the worst of all diseases."4 One might reasonably ask whether these descriptions constitute "media hype" or provide a true account of the magnitude of this problem. To appreciate the public health significance of Alzheimer's and other dementing diseases, it is useful to examine the change in the number of cases of dementia that has occurred in this century and to predict what changes will occur in this number during the first half of the 21st century. Assuming that the age-specific risk of being demented has not changed substantially during this century, estimates of the numbers of prevalent cases can be obtained from census data on age distributions' and from published data on the age-specific prevalence of dementing illnesses.6 The results of such an analysis for the population of the United States are shown in Figure 1. This analysis suggests that the number of prevalent cases of dementia in the United States has increased from fewer than 200,000 to close to 2 million in just the last 80 years. Of these cases of dementia, approximately 50 to 60% probably represent Alzheimer's disease, the remainder being due to a variety of different medical
conditions.7'8 Supported by Veterans Administration and NIH grant I-RO1-AG-01529. Address for reprint requests: James A. Mortimer, Ph.D., GRECC (11G), V.A. Medical Center, Minneapolis, MN 55417
Vol. 61, No. 4, May 1985
332
J.A. MORTIMER AND OTHERS
332
J.A.
MORTIMER
AND
OTHERS
4
,, 3 Ld
0 U) 2
z
0 -J
1900 1920 1940 1960 1980 2000 2020 2040 YEAR Fig. 1. Estimated number of prevalent
cases of dementia in the United
States, 1900-2030
The remarkable increase in the estimated number of people with dementia during this century can be attributed primarily to the increase in life expectancy that has occurred since 1900, allowing a much greater number of people to enter the period of high risk for this condition. By contrast, the predicted increase in the number of cases of dementia during the first half of the next century is principally the result of the postwar baby boom attaining old age. Therefore, even a modest increase in life expectancy over that predicted in census projections would substantially increase the number of dementia cases above that shown in Figure 1, since the risk of dementia remains high until at least age 90.6 While these numbers suggest that Alzheimer's disease and other dementias will pose a serious public health problem to American society in Bull. N.Y. Acad. Med.
333
DISEASE ALZHEIMER'S ALZHEIMEWS DIES
2018
w16t
/
FI14
12_/
L0 -
1980
1985
1990
1995
2000
YEAR Fig. 2. Estimated percentage of dementia cases in United States who
are
veterans, 1980-2000
general for several more decades, the problem faced by the Veterans Administration is more acute. The largest single group of former military personnel are veterans of World War II, who are just now entering the period of appreciable risk for Alzheimer's disease. The consequences of this unique age distribution are shown in Figure 2. Over the next 20 years, the proportion of all cases of dementia in the United States who are veterans will double from 10% to 20%. The impending increase in the number of veterans with dementing illnesses offers both a challenge and an opportunity for the Veterans Administration. The challenge is to develop effective management strategies to deal with the enormous increase in the number of veterans with Alzheimer's disease and related dementias who will require care. The opportunity is to utilize the Veterans Administration health care system to conduct the essential clinical and health systems research needed to develop a cost-effective strategy to manage the anticipated increase in the number of demented elderly people in the larger society before this problem reaches epidemic proportions in the next century. Vol. 61, No. 4, May 1985
334 334
J.A. MORTIMER AND OTHERS JA
OTMRADOHR
A RESEARCH AGENDA
The problem posed by dementia is multidisciplinary, and presents economic, medical, and public policy issues that must be addressed on several fronts, from basic research to highly sophisticated studies of health service delivery. In this paper we propose a research agenda for Alzheimer's disease and examine the present and future contributions by the Veterans Administration to addressing the issues in that agenda. While cure and prevention remain the ultimate goals of research on Alzheimer's disease, it is unlikely that an effort directed at one particular solution, e.g., the discovery of a medication that will halt or reverse the disease process, will provide an effective approach to the overall problem. At least five major research objectives can be identified: clinicallyeffective pharmacologic therapies, methods of early and accurate diagnosis, improved techniques to manage patients and evaluate the outcome of management strategies, cost-effective methods to deliver care to the demented elderly, and identifying the cause or causes of Alzheimer's disease. DEVELOPMENT OF AN EFFECTIVE PHARMACOLOGIC THERAPY
Considerable research effort is currently directed to find a drug that will have a clinically significant impact on the cognitive and memory disorders of Alzheimer's disease. Such a medication has not yet been found.9 The results of double-blind trials of medications that have been examined and shown to have some efficacy, including oral physostigmine,1012 naloxone,13 and piracetam,14 suggest that some patients improve while others do not, and that, with few exceptions, sensitive neuropsychological measures are required to demonstrate a response. An important research question that will arise should an effective medication be found is whether this drug will offer only symptomatic relief or will slow or halt disease progression. Presently, very little information is available on the efficacy of prolonged treatment of Alzheimer's disease patients using experimental medications. Figure 3 shows the results of a trial of lecithin and oral physostigmine in two patients with clinically-diagnosed Alzheimer's disease. These patients were studied by Thal and his coworkers11 for periods of 11 and 20 months, with placebo substituted for medication in the months indicated by the arrows. Following attainment of optimum improvement on Bull. N.Y. Acad. Med.
335
ALZHEIMER'S DISEASE
335
ALZHEIMER'S
e
23
Blessed Score
27
25
20
9
17
If
yn 45 Z 40
fen 35 W 30 9.u
25
6 20 '15 w
10 5
z ,v.
I
I
I
1
2
3 4
I
I
I
I
5 6 7 8 9 90 11 MONTHS
I
t
Fig. 3. Sum of recall (6) and retrieval from long term storage (x) in two Alzheimer patients during long-term treatment with a combination of lecithin and oral physostigmine. Arrows indicate months when placebo was given. Reproduced by permission from Thal, L. J., Masur, D. M., and Sharpless, N. S., et al.: Acute and Chronic Effects of Oral Physostigmine and Lecithin in Alzheimer's Disease. In: Alzheimer's Disease: Advances in Basic Research and Therapies, Wurtman, R.J., Corkin, S.H., and Growdon, J.H., editors. Boston, Center for Brain Sciences and Metabolism Charitable Trust, 1984, pp. 333-47.
'Oar LUJ
I--
Normal Average 0
751-
*
I-. cap
50F
Cs
25 v
1965
.
1970
1975 YEAR
I
.I
I
-r--l .
1980
Fig. 4. Sixteen-year history of maximum eye-hand tracking rate in a Parkinson patient treated with 1-dopa from 1971 (arrow) to 1983. All regressions shown are highly significant (p
