Efficacy of donepezil in mild cognitive impairment: a randomized placebo-controlled trial

Neurology. 2004 Aug 24;63(4):651-7. doi: 10.1212/01.wnl.0000134664.80320.92.


Objective: To evaluate the efficacy and safety of the acetylcholinesterase inhibitor donepezil in a placebo-controlled trial in patients with mild cognitive impairment (MCI).

Methods: A total of 270 patients with MCI were enrolled in a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Patients were randomized to receive donepezil (n = 133; 5 mg/day for 42 days, followed by forced dose escalation to 10 mg/day) or placebo (n = 137). Primary efficacy measures were the New York University (NYU) Paragraph Delayed Recall test and the Alzheimer disease (AD) Cooperative Study Clinician's Global Impression of Change for MCI (ADCS CGIC-MCI). Secondary efficacy measures included the modified AD Assessment Scale-cognitive subscale (ADAS-cog), the Patient Global Assessment (PGA), and additional neuropsychologic measures. Efficacy analyses were performed on intent-to-treat (ITT) and fully evaluable (FE) populations.

Results: Primary efficacy measures of the NYU Paragraph Recall test and the ADCS CGIC-MCI did not show significant treatment effects in the ITT population. Some secondary measures showed effects favoring donepezil. More donepezil-treated patients showed improvements in ADAS-cog total scores, in tests of attention and psychomotor speed, and in PGA scores. More donepezil-treated than placebo-treated patients experienced adverse events, most of which were mild to moderate and transient.

Conclusion: Although significant treatment effects were not seen in the primary efficacy measures, outcomes on secondary measures suggest promising directions for further evaluation of donepezil treatment in patients with MCI.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cholinesterase Inhibitors / administration & dosage
  • Cholinesterase Inhibitors / adverse effects
  • Cholinesterase Inhibitors / therapeutic use*
  • Cognition Disorders / drug therapy*
  • Donepezil
  • Double-Blind Method
  • Female
  • Humans
  • Indans / administration & dosage
  • Indans / adverse effects
  • Indans / therapeutic use*
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Nootropic Agents / administration & dosage
  • Nootropic Agents / adverse effects
  • Nootropic Agents / therapeutic use*
  • Piperidines / administration & dosage
  • Piperidines / adverse effects
  • Piperidines / therapeutic use*
  • Treatment Outcome


  • Cholinesterase Inhibitors
  • Indans
  • Nootropic Agents
  • Piperidines
  • Donepezil