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Original Article
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Volume 336:1216-1222 April 24, 1997 Number 17
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A Controlled Trial of Selegiline, Alpha-Tocopherol, or Both as Treatment for Alzheimer's Disease
Mary Sano, Ph.D., Christopher Ernesto, M.S., Ronald G. Thomas, Ph.D., Melville R. Klauber, Ph.D., Kimberly Schafer, M.S., Michael Grundman, M.D., M.P.H., Peter Woodbury, John Growdon, M.D., Carl W. Cotman, Ph.D., Eric Pfeiffer, M.D., Lon S. Schneider, M.D., Leon J. Thal, M.D., for The Members of the Alzheimer's Disease Cooperative Study

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ABSTRACT

Background There is evidence that medications or vitamins that increase the levels of brain catecholamines and protect against oxidative damage may reduce the neuronal damage and slow the progression of Alzheimer's disease.

Methods We conducted a double-blind, placebo-controlled, randomized, multicenter trial in patients with Alzheimer's disease of moderate severity. A total of 341 patients received the selective monoamine oxidase inhibitor selegiline (10 mg a day), alpha-tocopherol (vitamin E, 2000 IU a day), both selegiline and alpha-tocopherol, or placebo for two years. The primary outcome was the time to the occurrence of any of the following: death, institutionalization, loss of the ability to perform basic activities of daily living, or severe dementia (defined as a Clinical Dementia Rating of 3).

Results Despite random assignment, the base-line score on the Mini–Mental State Examination was higher in the placebo group than in the other three groups, and this variable was highly predictive of the primary outcome (P<0.001). In the unadjusted analyses, there was no statistically significant difference in the outcomes among the four groups. In analyses that included the base-line score on the Mini–Mental State Examination as a covariate, there were significant delays in the time to the primary outcome for the patients treated with selegiline (median time, 655 days; P = 0.012), alpha-tocopherol (670 days, P = 0.001), or combination therapy (585 days, P = 0.049), as compared with the placebo group (440 days).

Conclusions In patients with moderately severe impairment from Alzheimer's disease, treatment with selegiline or alpha-tocopherol slows the progression of disease.


Source Information

From the Gertrude H. Sergievsky Center, Department of Neurology, Columbia University College of Physicians and Surgeons, New York (M.S.); the Alzheimer's Disease Cooperative Study (C.E., R.G.T., M.R.K., K.S., M.G., P.W., L.J.T.) and the Departments of Family and Preventive Medicine (R.G.T., M.R.K.) and Neurosciences (M.G., L.J.T.), University of California at San Diego, La Jolla; the Department of Neurology, Harvard Medical School, Boston (J.G.); the University of California at Irvine, Irvine (C.W.C.); the University of South Florida, Tampa (E.P.); and the University of Southern California, Los Angeles (L.S.S.).

Address reprint requests to Dr. Sano at 630 W. 168th St., Box 16, New York, NY 10032.

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Related Letters:

Alpha-Tocopherol and Alzheimer's Disease
Pincus M. M., Kilander L., Öhrvall M., Sano M., Thomas R. G., Thal L. J.
Extract | Full Text  
N Engl J Med 1997; 337:572-573, Aug 21, 1997. Correspondence

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