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).
Conclusion: 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.
