A CONTROLLED TRIAL OF SELEGILINE, ALPHA-TOCOPHEROL, OR BOTH AS TREATMENT FOR ALZHEIMERS-DISEASE

Background There is evidence that medications or vitamins that increas e the levels of brain catecholamines and protect against oxidative dam age may reduce the neuronal damage and slow the progression of Alzheim er'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 mon oamine oxidase inhibitor selegiline (10 mg a day), alpha-tocopherol (v itamin E, 2000 IU a day), both selegiline and alpha-tocopherol, or pla cebo for two years. The primary outcome was the time to the occurrence of any of the following: death, institutionalization, loss of the abi lity to perform basic activities of daily living, or severe dementia ( defined as a Clinical Dementia Rating of 3). Results Despite random as signment, the baseline score on the Mini-Mental State Examination was higher in the placebo group than in the other three groups, and this v ariable was highly predictive of the primary outcome (P<0.001). In the unadjusted analyses, there was no statistically significant differenc e in the outcomes among the four groups. In analyses that included the base-line score on the Mini-Mental Stale Examination as a covariate, there were significant delays in the time to the primary outcome for t he 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 diseas e, treatment with selegiline or alpha-tocopherol slows the progression of disease. (C) 1997, Massachusetts Medical Society.