Synergistic associations of catechol-O-methyltransferase and brain-derived neurotrophic factor with executive function in aging are selective and modified by apolipoprotein E

Shraddha Sapkota, David Vergote, David Westaway, Jack Jhamandas, Roger A. Dixon
2015 Neurobiology of Aging  
Genetic polymorphisms of Catechol-O-methyltransferase (COMT) and Brain-derived neurotrophic factor (BDNF) have shown promising but inconsistent linkages with executive function (EF) in normal aging. We tested (a) independent contributions of COMT and BDNF risk, (b) potential magnification by risk-related interactions or additive effects with age, and (c) effect modification through stratification by Apolipoprotein E (APOE; risk (ε4+)). Multiple linear regression models were applied with
more » ... nted older adults (N = 634; range: 53-95 years) for an EF latent variable. No independent effects of BDNF or COMT on EF were observed. Additive (but not interactive) effects of COMT, BDNF, and age showed that older adults with a high-risk allelic combination performed differentially worse. Of two tested models of synergistic effects, the additive approach selectively supported a magnification hypothesis, which was qualified by the presence or absence of APOE ε4.
doi:10.1016/j.neurobiolaging.2014.06.020 pmid:25107496 pmcid:PMC4268316 fatcat:5hfm5vla7vagdc4kbmlfnnxjhy