APOE and BDNF Val66Met polymorphisms combine to influence episodic memory function in older adults.

Genetic polymorphisms of apolipoprotein E (APOE) and brain-derived neurotrophic factor (BDNF) have shown inconsistent associations with healthy adult cognitive functions. Recent investigations have suggested that APOE polymorphisms do not contribute to non-pathological cognitive function and that any effect is likely due to prodromal Alzheimer's disease (AD). Similarly, although BDNF Val66Met polymorphisms affect hippocampal morphology and function, associations with learning and/or memory have not always been found. This study sought to determine whether APOE and BDNF polymorphisms were associated, either independently or in combination, with adult cognition. Comprehensive neuropsychological assessments were conducted on 433 older adults, aged 50-79 years (M=62.16, SD=6.81), which yielded measures of episodic memory, working memory, executive function, and language processing. Participants underwent comprehensive neuropsychological assessment to ensure that only cognitively intact individuals comprised the sample. APOE and BDNF polymorphic data were used as predictors in general linear models that assessed composite cognitive domain variables, while covarying for education and age. Although no main effects for APOE or BDNF were found, the analysis identified a significant APOE×BDNF interaction that predicted episodic memory performance (p=.02, η(2)=.02). Post-hoc analyses demonstrated that in BDNF Val homozygotes, the cognitive consequences of APOE polymorphisms were minimal. However, in BDNF Met carriers, the hypothesized beneficial/detrimental effects of APOE polymorphisms were found. Our data show that concurrent consideration of both APOE and BDNF polymorphisms are required in order to witness a cognitive effect in healthy older adults.