title: Vitamin E and donepezil for the treatment of mild cognitive impairment.
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 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 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.
authors.affiliation: Mayo Clinic College of Medicine, Rochester, Minn, USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Thomas
authors.forename: Michael
authors.initials: M
authors.lastname: Grundman
authors.forename: David
authors.initials: D
authors.lastname: Bennett
authors.forename: Rachelle
authors.initials: R
authors.lastname: Doody
authors.forename: Steven
authors.initials: S
authors.lastname: Ferris
authors.forename: Douglas
authors.initials: D
authors.lastname: Galasko
authors.forename: Shelia
authors.initials: S
authors.lastname: Jin
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kaye
authors.forename: Allan
authors.initials: A
authors.lastname: Levey
authors.forename: Eric
authors.initials: E
authors.lastname: Pfeiffer
authors.forename: Mary
authors.initials: M
authors.lastname: Sano
authors.forename: Christopher H
authors.initials: CH
authors.lastname: van Dyck
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Thal
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000517:prevention & control*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy*; D018450:Disease Progression; D000077265:Donepezil; D004311:Double-Blind Method; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D017211:Treatment Failure; D014810:Vitamin E / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D014810:Vitamin E; D000077265:Donepezil