Metrifonate treatment of AD - Influence of APOE genotype

Objective: To investigate whether an interaction exists between APOE genoty pe and the response of AD patients to metrifonate treatment and whether APO E genotype independently affects the rate of AD progression. Background: Me trifonate is a new acetylcholinesterase inhibitor for the treatment of AD s ymptoms. Methods: Data were pooled from four prospective, randomized, doubl e-blind, placebo-controlled clinical trials and analyzed retrospectively. A total of 959 patients who received once-daily placebo (n = 374) or metrifo nate (30 to 60 mg based on weight or a 50-mg fixed dose, n = 585) for up to 26 weeks agreed to APOE genotyping. Results: Metrifonate clearly improved the cognitive performance of the AD patients when compared with placebo (Al zheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog], p = 0.000 1). The interaction of APOE genotype and the metrifonate effect on cognitiv e performance were not significant (p = 0.25). Metrifonate also clearly imp roved the global function of the AD patients when compared with placebo (Cl inician's Interview-Based Impression of Change with Caregiver Input [CIBIC- Plus], p = 0.0001). The interaction of APOE genotype with the metrifonate e ffect on global function also was not significant (p = 0.70). No significan t three-way interactions were observed among APOE genotype, gender, and res ponse to metrifonate treatment (ADAS-Cog, p = 0.68; CIBIC-Plus, p = 0.26). APOE genotype did not influence disease progression as evaluated by either cognitive performance (ADAS-Cog, p = 0.93) or global function (CIBIC-Plus, p = 0.64). Conclusions: The findings from these studies of up to 26 weeks' duration do not clearly support an interaction between APOE genotype and me trifonate treatment effects. They suggest that APOE genotypes do not necess arily predict an AD patient's response to metrifonate treatment and that AP OE genotype may not influence the rate of disease progression for patients with mild to moderate AD.