Presence or absence of at least one ε4 allele and gender are not predictive for the response to donepezil treatment in Alzheimer's disease

The objective was to evaluate the effects of the apolipoprotein E (ApoE) genotype and gender on the response to donepezil treatment in Alzheimer's disease. ApoE genotyping was performed on 117 patients with mild to moderate Alzheimer's disease who were included in a 36-week open label trial of donepezil therapy. Of these 117 patients, who constituted the intent-to-treat population (ITT), 80 completed the trial, and constituted the evaluable population. Patients were treated blindly in relation to ApoE genotype. Outcome measures were Alzheimer's disease Assessment Scale-Cognitive Component (ADASCog), the Mini Mental State Examination, Instrumental Activities of Daily Living, and the Caregiver-rated Clinical Global Impression of Change. ITT analysis did not reveal significant differences between the responses Of epsilon4- and epsilon4+ carriers according to the ADAS-Cog (P = 0.28). No differences were found either between the responses of men and women (P= 0.81), and there was no significant interaction between genotype and gender (P = 0.09). Other outcome measures all exhibited similar patterns of change to those seen using the ADAS-Cog. Consequently, these results do not support the hypothesis that the ApoE phenotype and gender are predictors of the response to donepezil in Alzheimer's disease patients.