title: APOE-ɛ4 Carrier Status and Donepezil Response in Patients with Alzheimer's Disease.
abstract: BACKGROUND
  Previous studies have investigated associations between apolipoprotein E (APOE)-ɛ4 allele status and acetylcholinesterase inhibitor treatment response in patients with Alzheimer's disease. The ability to draw definitive conclusions regarding the effect of APOE-ɛ4 genotype on treatment response has been hindered by inconsistent results among studies and methodological limitations that restrict interpretation of study findings.
  
  
  OBJECTIVE
  To determine whether APOE-ɛ4 carrier status influences the magnitude of change in 13-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) score associated with acetylcholinesterase inhibitor treatment (i.e., donepezil).
  
  
  METHODS
  Analyses were performed using pooled data from the donepezil and placebo treatment arms of three consecutive, similarly designed, 12-week, multi-national, randomized clinical studies that enrolled patients with mild-to-moderate Alzheimer's disease. Correlations between APOE-ɛ4 carrier status and ADAS-cog scores were evaluated using analysis of covariance.
  
  
  RESULTS
  No appreciable interaction between donepezil response and APOE-ɛ4 carrier status or copy number was detected. Both carriers and non-carriers of APOE-ɛ4 who received donepezil experienced significant improvements from baseline in ADAS-cog score versus placebo (p <  0.05). Change from baseline to final observation in the donepezil treatment group was - 2.95 for APOE-ɛ4 carriers and - 4.09 for non-carriers (p = 0.23). In contrast, non-carriers of APOE-ɛ4 in the placebo treatment group exhibited a greater improvement from baseline versus carriers (-2.38 versus - 0.60, p = 0.05).
  
  
  CONCLUSIONS
  Within this population, APOE genotype had no statistically significant effect on cognitive response to donepezil treatment; however, APOE-ɛ4 allele status was associated with a difference in the magnitude of the change in ADAS-cog of placebo-treated patients.
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Waring
authors.forename: Qi
authors.initials: Q
authors.lastname: Tang
authors.forename: Weining Z
authors.initials: WZ
authors.lastname: Robieson
authors.forename: David P
authors.initials: DP
authors.lastname: King
authors.forename: Ujjwal
authors.initials: U
authors.lastname: Das
authors.forename: Jordan
authors.initials: J
authors.lastname: Dubow
authors.forename: Sandeep
authors.initials: S
authors.lastname: Dutta
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Marek
authors.forename: Laura M
authors.initials: LM
authors.lastname: Gault
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010880:Piperidines / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales
chemical_list: D053327:Apolipoprotein E4; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil
keywords: Acetylcholinesterase inhibitors; apolipoprotein E; genotype; placebo effect; treatment efficacy