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Selegiline and Vitamin E for Alzheimer's Disease

Am Fam Physician. 1998 Jan 1;57(1):147.

Alzheimer's disease results in a loss of memory, cognition and judgment. Sano and associates investigated the use of selegiline (a mono-amine oxidase inhibitor), alpha-tocopherol (vitamin E), or a combination of the two in patients with moderately severe Alzheimer's disease to evaluate the effect of these agents in functional deterioration.

A total of 341 patients were recruited for the two-year study from 23 centers participating in the Alzheimer's Disease Cooperative Study. Study subjects were randomly assigned to receive selegiline (5 mg twice daily), alpha-tocopherol (1,000 IU twice daily), a combination of selegiline and alpha-tocopherol, or placebo. The principal goal of the study was to monitor the time until one of the following primary outcomes occurred: death, institutionalization, inability to perform at least two of three basic activities of daily living such as eating or using the toilet, or severe dementia. A secondary goal was to monitor measures of cognition, function and behavior.

Despite random assignment, baseline scores on cognitive testing were slightly higher in the placebo group than in the selegiline group. After adjusting for this finding in the statistical analysis, delays in the time to a primary outcome were found for patients taking selegiline (655 days), alpha-tocopherol (670 days) and combination therapy (585 days), compared with the placebo group (440 days). Patients treated with alpha-tocopherol alone experienced a statistically significant delay in institutionalization. Patients in all of the treatment groups also had significant delays in deterioration of the performance of activities of daily living.

Cognition did not improve in any of the groups. Also, patients in the treatment groups, especially in the group receiving combination therapy, experienced falls and syncope more often than did patients in the placebo group. However, these findings did not necessitate the discontinuation of treatment. Combination therapy did not offer additional benefit beyond that achieved with either agent alone, nor was one agent clearly superior to the other.

The authors conclude that issues such as cost and convenience remain important factors when selecting medication for patients with Alzheimer's disease. Little is known about the efficacy of these agents in other patient groups, such as those with mild cognitive impairment or those with early- or late-stage Alzheimer's disease, since this study was confined to patients with moderately severe Alzheimer's disease.

Sano M, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. N Engl J Med. 1997;336:1216–22.


Copyright © 1998 by the American Academy of Family Physicians.
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