Vitamin E and donepezil for the treatment of mild cognitive impairment

Ronald C. Petersen, Ronald G. Thomas, Michael Grundman, David Bennett, Rachelle Doody, Steven Ferris, Douglas Galasko, Shelia Jin, Jeffrey Kaye, Allan Levey, Eric Pfeiffer, Mary Sano, Christopher H. Van Dyck, Leon J. Thal

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Abstract

BACKGROUND: Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and 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 e 4 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 e 4 carriers. CONCLUSIONS: Vitamin E had no benefit in patients with mild cognitive impairment. Although donepezil therapy was associated with a lower rate of progression to Alzheimer's disease during the first 12 months of treatment, the rate of progression to Alzheimer's disease after three years was not lower among patients treated with donepezil than among those given placebo.

Original languageEnglish (US)
Pages (from-to)2379-2388
Number of pages10
JournalNew England Journal of Medicine
Volume352
Issue number23
DOIs
StatePublished - Jun 9 2005

ASJC Scopus subject areas

  • Medicine(all)

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    Petersen, R. C., Thomas, R. G., Grundman, M., Bennett, D., Doody, R., Ferris, S., Galasko, D., Jin, S., Kaye, J., Levey, A., Pfeiffer, E., Sano, M., Van Dyck, C. H., & Thal, L. J. (2005). Vitamin E and donepezil for the treatment of mild cognitive impairment. New England Journal of Medicine, 352(23), 2379-2388. https://doi.org/10.1056/NEJMoa050151