Donepezil HCl (E2020) maintains functional brain activity in patients with Alzheimer disease: results of a 24-week, double-blind, placebo-controlled study

Am J Geriatr Psychiatry. 2003 Mar-Apr;11(2):169-77.


Objective: The authors evaluated the effects of donepezil (10 mg/day) versus placebo on brain glucose metabolism.

Methods: This was a randomized, double-blind, parallel-group, 24-week pilot study in 28 patients with mild-to-moderate Alzheimer disease (AD). Functional brain activity was quantified by measuring average glucose metabolism in an axial brain slice and regional brain glucose metabolism using positron emission tomography.

Results: At Week 24, relative to the pons metabolic rate, mean brain glucose metabolism in an axial slice at the level of the striatum was maintained within 0.5% of mean baseline levels for donepezil-treated patients, whereas it declined by an average of 10.4% in placebo-treated patients. This observation was confirmed by an analysis of differences in the mean slopes of glucose metabolism in the striatal slice in donepezil- and placebo-treated patients during the 24-week period. Significant treatment differences at Week 24 favoring donepezil for the mean percentage change from baseline in regional brain glucose metabolism were observed in four predefined regions of interest: the right parietal lobe 1, left temporal lobe 2, right frontal lobe 2, and left frontal lobe 2.

Conclusion: Placebo-treated patients with AD show a decline in functional brain activity, relative to the pons, in several regions, and treatment with donepezil may slow this decline.

Publication types

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

MeSH terms

  • Aged
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / drug therapy*
  • Brain / anatomy & histology
  • Brain / drug effects*
  • Brain / metabolism*
  • Cholinesterase Inhibitors / pharmacology*
  • Cholinesterase Inhibitors / therapeutic use*
  • Cognition Disorders / diagnosis
  • Donepezil
  • Double-Blind Method
  • Female
  • Fluorodeoxyglucose F18 / pharmacokinetics
  • Glucose / metabolism*
  • Humans
  • Indans / pharmacology*
  • Indans / therapeutic use*
  • Magnetic Resonance Imaging
  • Male
  • Neuropsychological Tests
  • Pilot Projects
  • Piperidines / pharmacology*
  • Piperidines / therapeutic use*
  • Radiopharmaceuticals / pharmacokinetics
  • Severity of Illness Index
  • Tomography, Emission-Computed


  • Cholinesterase Inhibitors
  • Indans
  • Piperidines
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Donepezil
  • Glucose