A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study

N Engl J Med. 1997 Apr 24;336(17):1216-22. doi: 10.1056/NEJM199704243361704.


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 baseline 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activities of Daily Living*
  • Aged
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / mortality
  • Cognition / drug effects
  • Disease Progression
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Humans
  • Institutionalization
  • Male
  • Mental Status Schedule
  • Monoamine Oxidase Inhibitors / therapeutic use*
  • Proportional Hazards Models
  • Selegiline / therapeutic use*
  • Treatment Outcome
  • Vitamin E / therapeutic use*


  • Drug Combinations
  • Monoamine Oxidase Inhibitors
  • Vitamin E
  • Selegiline