1. ¹Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA
2. ²Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
3. ³Novartis Pharmaceuticals Corporation, Gaithersburg, MD, USA

Correspondence: Dr M Farlow, Department of Neurology, Clinical Building, Room 299, 541 Clinical Drive, Indiana University School of Medicine, Indianapolis, IN 46202-5111, USA. Tel: +1 317 274 2893; Fax: +1 317 278 3930; E-mail: mfarlow@iupui.edu

Received 18 August 2003; Revised 27 May 2004; Accepted 8 June 2004; Published online 3 August 2004.

Abstract

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) 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 4 and non-APOE 4 subgroups comprised 246 and 121 patients, respectively. Overall, APOE 4 noncarriers showed greater decline than carriers (P<0.05). However, at 26 weeks, placebo-treated APOE 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 4 placebo-treated patients declined by 4.59 points and rivastigmine-treated patients declined by 0.48 points. Thus, non-APOE 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).