Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease

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 epsilon(4) allele status and ADAS-Cog (P=0.014). Exploratory analyses demonstrated significant improvement in ADAS-Cog in APOE epsilon(4)-negative patients on 8mg RSG (P=0.024; not corrected for multiplicity). APOE epsilon 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 epsilon 4 non-carriers exhibited cognitive and functional improvement in response to RSG, whereas APOE epsilon 4 allele carriers showed no improvement and some decline was noted. These preliminary findings require confirmation in appropriate clinical studies.