Differential qualitative responses to rivastigmine in APOE epsilon 4 carriers and noncarriers

This retrospective analysis of two double-blind, placebo-controlled studies in patients with mild to moderately severe AD investigated the efficacy of rivastigmine 6-12 mg/day on cognitive outcomes in patients with or without the apolipoprotein (APOE) epsilon 4 allele. APOE data were collected from patients who consented to pharmacogenetic testing. Treatment differences within each subgroup were compared, using the Observed Case (OC) population. The APOE epsilon 4 and non-APOE epsilon 4 subgroups comprised 246 and 121 patients, respectively. Overall, APOE epsilon 4 noncarriers showed greater decline than carriers (P < 0.05). However, at 26 weeks, placebo-treated APOE epsilon 4 patients declined 3.04 points below baseline on the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), and rivastigmine-treated patients improved by 1.67 points. Non-APOE epsilon 4 placebo-treated patients declined by 4.59 points and rivastigmine-treated patients declined by 0.48 points. Thus, non-APOE epsilon 4 carriers showed a less favorable course under either placebo or rivastigmine, but both genotype-defined subgroups showed quantitatively similar responses to therapy (both P < 0.05 vs placebo).