Combined Genetic Influences on Episodic Memory Decline in Older Adults Without Dementia

Objective: Although heritability explains a large proportion of the variance in old-age cognition, studies on the influence of specific genes have been inconclusive. We investigated the individual and combined effects of four single polymorphisms, previously associated with episodic memory, on cognitive or performance and rate of change. Method: Participants were 2490 individuals without dementia (mean age = 72 years) from the population-based Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). Genotyping was performed for APOE (rs429358, rs7412), BDNF (rs6265), KIBRA (rs17070145), and CLSTN2 (rs6439886). We used latent difference score models to estimate the effects of age and genetic variation on level and change in five latent cognitive factors: episodic and semantic memory, letter and category fluency, and perceptual speed. Results: Of the individual genes, only APOE was associated with cognitive performance; epsilon 4 carriers showed lower perceptual speed performance and faster category fluency decline. A cumulative score, combining APOE, BDNF, KIBRA and CLSTN2, was associated with faster cognitive decline that was specific to the episodic memory domain (regression coefficient -0.064, p < .01). Similar results were obtained for a score not including APOE. Conclusions: Results suggest a benefit of investigating the combined influence of polymorphisms related to specific mechanistic factors.