This study evaluated the effects of vitamin E and donepezil on the progression from mild cognitive impairment (MCI) to Alzheimer's disease. The study was a randomized, double-blind, placebo-controlled trial involving 769 subjects with amnestic MCI. Participants were randomly assigned to receive either 2000 IU of vitamin E daily, 10 mg of donepezil daily, or a placebo for three years. The primary outcome was the development of possible or probable Alzheimer's disease, while secondary outcomes included cognition and function. Key findings: - The overall rate of progression from MCI to Alzheimer's disease was 16% per year. - There were no significant differences in the probability of progression to Alzheimer's disease between the vitamin E group and the placebo group (hazard ratio, 1.02; 95% CI, 0.74 to 1.41; P=0.91). - There were no significant differences in the probability of progression to Alzheimer's disease between the donepezil group and the placebo group (hazard ratio, 0.80; 95% CI, 0.57 to 1.13; P=0.42). - Donepezil reduced the risk of progression to Alzheimer's disease during the first 12 months of the trial (P=0.04 at 6 months and P=0.04 at 12 months). - Among APOE ε4 carriers, donepezil reduced the risk of progression to Alzheimer's disease throughout the three-year study period. - Vitamin E had no significant effect on the development of Alzheimer's disease at any time point. - Donepezil treatment did not significantly affect overall cognitive function but delayed cognitive decline in the first 6 to 18 months. The study concluded that vitamin E had no benefit in preventing the progression from MCI to Alzheimer's disease, while donepezil showed a reduced likelihood of progression during the first year but not over the entire three-year period. The results suggest that donepezil may be beneficial for APOE ε4 carriers but do not provide a clear recommendation for its use in MCI.This study evaluated the effects of vitamin E and donepezil on the progression from mild cognitive impairment (MCI) to Alzheimer's disease. The study was a randomized, double-blind, placebo-controlled trial involving 769 subjects with amnestic MCI. Participants were randomly assigned to receive either 2000 IU of vitamin E daily, 10 mg of donepezil daily, or a placebo for three years. The primary outcome was the development of possible or probable Alzheimer's disease, while secondary outcomes included cognition and function. Key findings: - The overall rate of progression from MCI to Alzheimer's disease was 16% per year. - There were no significant differences in the probability of progression to Alzheimer's disease between the vitamin E group and the placebo group (hazard ratio, 1.02; 95% CI, 0.74 to 1.41; P=0.91). - There were no significant differences in the probability of progression to Alzheimer's disease between the donepezil group and the placebo group (hazard ratio, 0.80; 95% CI, 0.57 to 1.13; P=0.42). - Donepezil reduced the risk of progression to Alzheimer's disease during the first 12 months of the trial (P=0.04 at 6 months and P=0.04 at 12 months). - Among APOE ε4 carriers, donepezil reduced the risk of progression to Alzheimer's disease throughout the three-year study period. - Vitamin E had no significant effect on the development of Alzheimer's disease at any time point. - Donepezil treatment did not significantly affect overall cognitive function but delayed cognitive decline in the first 6 to 18 months. The study concluded that vitamin E had no benefit in preventing the progression from MCI to Alzheimer's disease, while donepezil showed a reduced likelihood of progression during the first year but not over the entire three-year period. The results suggest that donepezil may be beneficial for APOE ε4 carriers but do not provide a clear recommendation for its use in MCI.