Journal
NEUROBIOLOGY OF AGING
Volume 36, Issue 1, Pages 249-256Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2014.06.020
Keywords
Aging; Executive function; Apolipoprotein E; Catechol-O-methyltransferase; Brain-derived neurotrophic factor; Victoria longitudinal study
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Funding
- National Institutes of Health [R01 AG008235]
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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: epsilon 4+). 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 epsilon 4. (C) 2015 Elsevier Inc. All rights reserved.
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