Effect of ApoE genotype on response to donepezil in patients with Alzheimer's disease

Dement Geriatr Cogn Disord. 2008;25(5):445-50. doi: 10.1159/000124752. Epub 2008 Apr 10.

Abstract

Background/aims: The possible influence of apolipoprotein E (ApoE) genotype on the response to acetylcholinesterase inhibitor therapy in patients with Alzheimer's disease (AD) remains a matter of controversy. In order to address this issue, we investigated the effects of ApoE genotype on the clinical response to donepezil in patients with mild to moderate AD.

Methods: An open study was carried out in 51 patients with probable AD who were treated with 5-10 mg of donepezil per day for 48 weeks.

Results: Eighteen (35.3%) of the 51 patients had 1 or 2 ApoE epsilon4 alleles. ApoE epsilon4 carriers with AD showed a mean 1.1-point increase from the baseline score of 23.9 on the 70-point Alzheimer's Disease Assessment Scale-Cognitive Component at 48 weeks, while the ApoE epsilon4 noncarrier group showed a 3.1-point increase from the baseline score of 22.5 (p = 0.03). The ApoE epsilon4 carrier group exhibited a mean 0.13-point worsening from the baseline score of 0.97 on the Korean Instrumental Activities of Daily Living at 48 weeks, while the ApoE epsilon4 noncarrier group exhibited a 0.17-point worsening from the baseline score of 0.64 (p = 0.05).

Conclusion: AD patients who carry the ApoE epsilon4 allele may respond more favorably to donepezil than epsilon4 noncarriers.

Publication types

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

MeSH terms

  • Aged
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics*
  • Apolipoprotein E4 / genetics*
  • Donepezil
  • Drug Resistance / genetics
  • Female
  • Follow-Up Studies
  • Genotype
  • Humans
  • Indans / therapeutic use*
  • Male
  • Middle Aged
  • Nootropic Agents / therapeutic use*
  • Piperidines / therapeutic use*
  • Treatment Outcome

Substances

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