Treatment outcome of tacrine therapy depends on apolipoprotein genotype and gender of the subjects with Alzheimer's disease

Abstract

We studied the effects of apolipoprotein E (<i>APOE</i>) genotype and gender on clinical response to tacrine in patients with mild to moderate Alzheimer9s disease (AD). We analyzed data from a previously reported 30-week, double-blind, placebo-controlled trial of tacrine, in which <i>APOE</i> genotypes were determined from previously collected plasma samples. Patients were assigned to placebo or tacrine with daily dosages of 80, 120, or 160 mg/day. The outcome measures were Alzheimer9s Disease Assessment Scale-Cognitive Component, Clinician Interview Based Impression, Mini-Mental State Examination, and the Caregiver-rated Clinical Global Impression of Change. An intent-to-treat (ITT) analysis of patients with available genotypes (n = 528) did not reveal response differences by genotype, although the effect size was twice as large in the ϵ2-3 as theϵ4 group (-2.62 versus -1.25). The association of treatment effect with <i>APOE</i> genotype varied significantly according to gender (<i>p</i>&lt; 0.002 for ITT; <i>p</i> &lt; 0.05 for evaluables). The treatment effect was larger in the ϵ2-3 compared with ϵ4 women (ITT, 4.24 points, <i>p</i> = 0.03; evaluable, 7.20 points, <i>p</i> = 0.01). In contrast, treatment effect size was not different between ϵ2-3 andϵ4 of men with AD. <i>APOE</i> genotype and gender may predict response to tacrine in patients with AD.