title: Synergistic associations of catechol-O-methyltransferase and brain-derived neurotrophic factor with executive function in aging are selective and modified by apolipoprotein E.
abstract: 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 (1) independent contributions of COMT and BDNF risk; (2) potential magnification by risk-related interactions or additive effects with age; and (3) effect modification through stratification by apolipoprotein E (APOE) (risk: ε4+). Multiple linear regression models were applied with nondemented 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 2 tested models of synergistic effects, the additive approach selectively supported a magnification hypothesis, which was qualified by the presence or the absence of APOE ε4.
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Shraddha
authors.initials: S
authors.lastname: Sapkota
authors.affiliation: Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Vergote
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada; Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Westaway
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada; Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jack
authors.initials: J
authors.lastname: Jhamandas
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada; Department of Psychology, University of Alberta, Edmonton, Alberta, Canada. Electronic address: rdixon@ualberta.ca.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Dixon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000502:physiology*; D001057:Apolipoproteins E / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000502:physiology*; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000502:physiology*; D004843:Epistasis, Genetic / Q000235:genetics*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: D001057:Apolipoproteins E; D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: Aging; Apolipoprotein E; Brain-derived neurotrophic factor; Catechol-O-methyltransferase; Executive function; Victoria longitudinal study
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