Investigating Gene-Gene Interactions By Cognitive Domain In Healthy Older Adults

Abstract Objective ApoE is a well-known gene carrying risk for Alzheimer’s disease and is associated with memory performance while the COMT gene is associated with executive functioning but is understudied. The present study investigated these gene interactions across cognitive domains. Method A larger study on gait and aging recruited 89 healthy community-dwelling adults over the age of 60. The primary analyses included 82 participants (67% female, mean age = 74.61, SD = 6.71). The analyses on executive functioning included 72 participants (65% female, mean age = 73.02, SD = 4.99) who completed all measures of interest. ApoE status was defined as presence/absence of Ɛ4. The rs4680 gene on the COMT allele was classified into Val/Met, Val/Val, and Met/Met genotypes. Biological sex was included as a binary term (i.e., male/female). Index variables and age corrected standard scores on the Repeatable Battery for the Assessment of Neuropsychological Status, verbal fluency, and Trail Making Test were included. Results Gene–gene interactions were found for overall cognitive functioning, immediate memory, and semantic fluency. There were main effects of sex for overall cognitive functioning, immediate memory, delayed memory, and semantic fluency. There were main effects for COMT for delayed memory and a main effect for both COMT and ApoE for visuospatial functioning, coding, and verbal fluency (all p’s < 0.05). There were no ApoE x COMT x Sex interactions and Trail Making Test B was not related to either gene or sex. Conclusion(s) Our findings suggest that both COMT and ApoE (and their interaction) influence cognition. Future research should investigate gene–gene interactions in larger samples with more comprehensive cognitive batteries.