1. APOE-ɛ4 Carrier Status and Donepezil Response in Patients with Alzheimer’s Disease
- Author
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Weining Z. Robieson, Jeffrey F. Waring, Sandeep Dutta, Jordan Dubow, Ujjwal Das, Laura M. Gault, David P. King, Qi Tang, and Gerard Marek
- Subjects
Male ,Apolipoprotein E ,medicine.medical_specialty ,medicine.drug_class ,genotype ,Apolipoprotein E4 ,Population ,Disease ,Neuropsychological Tests ,Placebo ,Cognition ,Double-Blind Method ,treatment efficacy ,Piperidines ,Alzheimer Disease ,Internal medicine ,mental disorders ,medicine ,Humans ,Donepezil ,education ,Psychiatry ,Aged ,apolipoprotein E ,Cholinesterase ,Aged, 80 and over ,Psychiatric Status Rating Scales ,education.field_of_study ,biology ,General Neuroscience ,General Medicine ,Middle Aged ,medicine.disease ,Psychiatry and Mental health ,Clinical Psychology ,Acetylcholinesterase inhibitors ,Acetylcholinesterase inhibitor ,Indans ,biology.protein ,placebo effect ,Female ,Cholinesterase Inhibitors ,Geriatrics and Gerontology ,Alzheimer's disease ,Psychology ,Research Article ,medicine.drug - Abstract
Background: Previous studies have investigated associations between apolipoprotein E (APOE)-ɛ4 allele status and acetylcholinesterase inhibitor treatment response in patients with Alzheimer’s disease. The ability to draw definitive conclusions regarding the effect of APOE-ɛ4 genotype on treatment response has been hindered by inconsistent results among studies and methodological limitations that restrict interpretation of study findings. Objective: To determine whether APOE-ɛ4 carrier status influences the magnitude of change in 13-item Alzheimer’s Disease Assessment Scale−Cognitive Subscale (ADAS-cog) score associated with acetylcholinesterase inhibitor treatment (i.e., donepezil). Methods: Analyses were performed using pooled data from the donepezil and placebo treatment arms of three consecutive, similarly designed, 12-week, multi-national, randomized clinical studies that enrolled patients with mild-to-moderate Alzheimer’s disease. Correlations between APOE-ɛ4 carrier status and ADAS-cog scores were evaluated using analysis of covariance. Results: No appreciable interaction between donepezil response and APOE-ɛ4 carrier status or copy number was detected. Both carriers and non-carriers of APOE-ɛ4 who received donepezil experienced significant improvements from baseline in ADAS-cog score versus placebo (p < 0.05). Change from baseline to final observation in the donepezil treatment group was – 2.95 for APOE-ɛ4 carriers and – 4.09 for non-carriers (p = 0.23). In contrast, non-carriers of APOE-ɛ4 in the placebo treatment group exhibited a greater improvement from baseline versus carriers (–2.38 versus – 0.60, p = 0.05). Conclusion: Within this population, APOE genotype had no statistically significant effect on cognitive response to donepezil treatment; however, APOE-ɛ4 allele status was associated with a difference in the magnitude of the change in ADAS-cog of placebo-treated patients.
- Published
- 2015