Clinical Response to Donepezil in Mild and Moderate Dementia: Relationship to Drug Plasma Concentration and CYP2D6 and APOE Genetic Polymorphisms

J Alzheimers Dis. 2017;55(2):539-549. doi: 10.3233/JAD-160164.

Abstract

The clinical response to donepezil in patients with mild and moderate dementia was investigated in relation to the drug plasma concentration and APOE and CYP2D6 polymorphisms. In a prospective naturalistic observational study, 42 patients with Alzheimer's disease (AD) and AD with cerebrovascular disease who took donepezil (10 mg) for 12 months were evaluated. Their DNA was genotyped, and the donepezil plasma concentrations were measured after 3, 6, and 12 months. Good responders scored ≥-1 on the Mini-Mental State Examination at 12 months in comparison to the baseline score. The study results indicated the good response pattern was influenced by the concentration of donepezil, but not by APOE and CYP2D6 polymorphisms.

Keywords: APOE; Alzheimer’s disease; CYP2D6; donepezil; genetics; naturalistic study.

Publication types

  • Observational Study

MeSH terms

  • Apolipoproteins E / genetics*
  • Cholinesterase Inhibitors / blood*
  • Cholinesterase Inhibitors / therapeutic use*
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP2D6 / genetics*
  • Dementia* / blood
  • Dementia* / drug therapy
  • Dementia* / genetics
  • Donepezil
  • Female
  • Follow-Up Studies
  • Humans
  • Indans / blood*
  • Indans / therapeutic use*
  • Male
  • Mental Status and Dementia Tests
  • Neuropsychological Tests
  • Piperidines / blood*
  • Piperidines / therapeutic use*
  • Polymorphism, Single Nucleotide / genetics*
  • Time Factors

Substances

  • Apolipoproteins E
  • Cholinesterase Inhibitors
  • Indans
  • Piperidines
  • Donepezil
  • Cytochrome P-450 CYP2D6