APOE-?4 Carrier Status and Donepezil Response in Patients with Alzheimer's Disease.
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ABSTRACT: Previous studies have investigated associations between apolipoprotein E (APOE)-?4 allele status and acetylcholinesterase inhibitor treatment response in patients with Alzheimer's disease. The ability to draw definitive conclusions regarding the effect of APOE-?4 genotype on treatment response has been hindered by inconsistent results among studies and methodological limitations that restrict interpretation of study findings.To determine whether APOE-?4 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).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-?4 carrier status and ADAS-cog scores were evaluated using analysis of covariance.No appreciable interaction between donepezil response and APOE-?4 carrier status or copy number was detected. Both carriers and non-carriers of APOE-?4 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-?4 carriers and - 4.09 for non-carriers (p?=?0.23). In contrast, non-carriers of APOE-?4 in the placebo treatment group exhibited a greater improvement from baseline versus carriers (-2.38 versus - 0.60, p?=?0.05).Within this population, APOE genotype had no statistically significant effect on cognitive response to donepezil treatment; however, APOE-?4 allele status was associated with a difference in the magnitude of the change in ADAS-cog of placebo-treated patients.
SUBMITTER: Waring JF
PROVIDER: S-EPMC4923746 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
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