Effect of the apolipoprotein E epsilon 4 allele on the efficacy and tolerability of galantamine in the treatment of Alzheimer's disease

Objective: To investigate the effect of the apolipoprotein E (ApoE) epsilon 4 allele on the efficacy and tolerability of galantamine treatment. Methods: A total of 202 patients with mild to moderate Alzheimer's disease participated in a 16-week, prospective, multi-center, randomized, double-blind galantamine trial in a Korean population. Patients were assessed at baseline and after 4, 8 and 16 weeks of randomized treatment using the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog/11), the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the Disability Assessment for Dementia Scale (DAD), the Behavioural Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) and adverse events. ApoE genotypes were determined for all subjects. Results: Of the 202 subjects, 115 carried at least one ApoE epsilon 4 allele and 87 did not. In both ApoE epsilon 4 carriers and ApoE epsilon 4 noncarriers, significant improvements were detected relative to baseline on ADAS-cog/11, CIBIC-plus, DAD and BEHAVE-AD. ApoE epsilon 4 noncarriers showed better improvement in mean total BEHAVE-AD score and mean psychosis (delusions and hallucinations) subscale score than ApoE epsilon 4 carriers. The incidence of weight loss was significantly higher in ApoE epsilon 4 carriers (n = 11; 9.6%) than in ApoE epsilon 4 noncarriers (n = 1; 1.2%) during this 16-week study, even though 92% of patients who complained of weight loss completed this 16-week trial successfully. Conclusion: ApoE epsilon 4 genotype does not affect galantamine-related improvements in cognition, global rating, function and behavior. Longer prospective studies with larger patient populations are required to confirm these new findings. Copyright (C) 2006 S. Karger AG, Basel.