Petersen RC, Thomas RG, Grundman M, et al: Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med 2005;352;2(3):2379-88.
Blacker D: Mild cognitive impairment-no benefit from vitamin E, little from donepezil. N Engl J Med 2005;352;2:(3):2439-41(editorial).
In a double-blind study, 769 subjects with the amnesic subtype of mild cognitive impairment were randomly assigned to receive vitamin E 2,000 units daily, donepezil (Aricept) 10 mg daily, or placebo for 3 years. Possible or probable Alzheimer's disease developed in 212 subjects with no significant differences in the probability of progression to Alzheimer's disease in the vitamin E group (hazard ratio = 1.02) or the donepezil group (HR = 0.80). Compared with the placebo group, the donepezil group progressed more slowly to Alzheimer's disease at first (p = 0.04 during the first 12 months). In those study subjects with apolipoprotein E e4 alleles, the benefit of donepezil was significant at each analysis throughout the 3-year follow-up. Vitamin E had no benefit at any point, either among all patients or among the apolipoprotein E e4 carriers.