Vitamin E and Donepezil for the Treatment
of Mild Cognitive Impairment
by
Petersen RC, Thomas RG, Grundman M, Bennett D, Doody R,
Ferris S, Galasko D, Jin S, Kaye J,
Levey A, Pfeiffer E, Sano M, van Dyck CH, Thal LJ
N Engl J Med. 2005 Apr 13

ABSTRACT

Background Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and very early Alzheimer's disease. Methods In a double-blind study, we evaluated subjects with the amnestic subtype of mild cognitive impairment. Subjects were randomly assigned to receive 2000 IU of vitamin E daily, 10 mg of donepezil daily, or placebo for three years. The primary outcome was clinically possible or probable Alzheimer's disease; secondary outcomes were cognition and function. Results A total of 769 subjects were enrolled, and possible or probable Alzheimer's disease developed in 212. The overall rate of progression from mild cognitive impairment to Alzheimer's disease was 16 percent per year. As compared with the placebo group, there were no significant differences in the probability of progression to Alzheimer's disease in the vitamin E group (hazard ratio, 1.02; 95 percent confidence interval, 0.74 to 1.41; P=0.91) or the donepezil group (hazard ratio, 0.80; 95 percent confidence interval, 0.57 to 1.13; P=0.42) during the three years of treatment. Prespecified analyses of the treatment effects at 6-month intervals showed that as compared with the placebo group, the donepezil group had a reduced likelihood of progression to Alzheimer's disease during the first 12 months of the study (P=0.04), a finding supported by the secondary outcome measures. Among carriers of one or more apolipoprotein E epsilon4 alleles, the benefit of donepezil was evident throughout the three-year follow-up. There were no significant differences in the rate of progression to Alzheimer's disease between the vitamin E and placebo groups at any point, either among all patients or among apolipoprotein E epsilon4 carriers. Conclusions Vitamin E had no benefit in patients with mild cognitive impairment. Although after three years, the rate of progression to Alzheimer's disease was not lower among patients treated with donepezil than among those given placebo, donepezil therapy was associated with a lower rate of progression to Alzheimer's disease during the first 12 months of treatment.

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Idebenone
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Meclofenoxate
New brain cells
Centrophenoxine
Alzhemer's disease
The memory switch?
Dumb-drug euphoria
Growing new brain cells
Piracetam and working memory
Donepezil (Aricept) for the drug-addled
Alzheimer's Disease: resources and hotlinks
Acute efects of donepezil (Aricept) in young healthy volunteers

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