1. ¹World Wide Development, Research and Development, GlaxoSmithKline, Research Triangle Park, NC, USA
2. ²Genetics Research, Research and Development, GlaxoSmithKline, Research Triangle Park, NC, USA
3. ³World Wide Development, Research and Development, GlaxoSmithKline, Harlow, UK
4. ⁴World Wide Development, Research and Development, GlaxoSmithKline, Greenford, UK
5. ⁵Geriatric Research Education and Clinical Center, VA Puget Sound, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA

Correspondence: Dr ME Risner, World Wide Development, Research and Development, GlaxoSmithKline Inc., Five Moore Drive (MAI-C4497), Research Triangle Park, NC 27709-3398, USA. E-mail: Marc.E.Risner@gsk.com

Received 14 November 2005; Revised 29 November 2005; Accepted 30 November 2005; Published online 31 January 2006.

Abstract

Mild-to-moderate AD patients were randomized to placebo or rosiglitazone (RSG) 2, 4 or 8 mg. Primary end points at Week 24 were mean change from baseline in AD Assessment Scale-Cognitive (ADAS-Cog) and Clinician's Interview-Based Impression of Change Plus Caregiver Input global scores in the intention-to-treat population (N=511), and results were also stratified by apolipoprotein E (APOE) genotype (n=323). No statistically significant differences on primary end points were detected between placebo and any RSG dose. There was a significant interaction between APOE 4 allele status and ADAS-Cog (P=0.014). Exploratory analyses demonstrated significant improvement in ADAS-Cog in APOE 4-negative patients on 8 mg RSG (P=0.024; not corrected for multiplicity). APOE 4-positive patients did not show improvement and showed a decline at the lowest RSG dose (P=0.012; not corrected for multiplicity). Exploratory analyses suggested that APOE 4 non-carriers exhibited cognitive and functional improvement in response to RSG, whereas APOE 4 allele carriers showed no improvement and some decline was noted. These preliminary findings require confirmation in appropriate clinical studies.