Presence or absence of at least one epsilon 4 allele and gender are not predictive for the response to donepezil treatment in Alzheimer's disease

Pharmacogenetics. 2002 Jul;12(5):415-20. doi: 10.1097/00008571-200207000-00009.


The objective was to evaluate the effects of the apolipoprotein E (ApoE) genotype and gender on the response to donepezil treatment in Alzheimer's disease. ApoE genotyping was performed on 117 patients with mild to moderate Alzheimer's disease who were included in a 36-week open label trial of donepezil therapy. Of these 117 patients, who constituted the intent-to-treat population (ITT), 80 completed the trial, and constituted the evaluable population. Patients were treated blindly in relation to ApoE genotype. Outcome measures were Alzheimer's disease Assessment Scale-Cognitive Component (ADAS-Cog), the Mini Mental State Examination, Instrumental Activities of Daily Living, and the Caregiver-rated Clinical Global Impression of Change. ITT analysis did not reveal significant differences between the responses of epsilon 4- and epsilon 4+ carriers according to the ADAS-Cog (P = 0.28). No differences were found either between the responses of men and women (P = 0.81), and there was no significant interaction between genotype and gender (P = 0.09). Other outcome measures all exhibited similar patterns of change to those seen using the ADAS-Cog. Consequently, these results do not support the hypothesis that the ApoE phenotype and gender are predictors of the response to donepezil in Alzheimer's disease patients.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics*
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Donepezil
  • Educational Status
  • Female
  • Humans
  • Indans / therapeutic use*
  • Male
  • Nootropic Agents / therapeutic use*
  • Piperidines / therapeutic use*
  • Predictive Value of Tests
  • Sex Characteristics


  • Apolipoprotein E4
  • Apolipoproteins E
  • Indans
  • Nootropic Agents
  • Piperidines
  • Donepezil