Depression and Cognitive Dysfunction in Older U.S. Military Veterans: Moderating Effects of BDNF Val66Met Polymorphism and Physical Exercise

• Published in: The American journal of geriatric psychiatry 2020-09, Vol.28 (9), p.959-967
• Main Authors: Pitts, Barbara L., Wen, Vivian, Whealin, Julia M., Fogle, Brienna M., Southwick, Steven M., Esterlis, Irina, Pietrzak, Robert H.
• Format: Article
• Language: English
• Subjects: Brain-derived neurotrophic factor; Cognitive ability; cognitive function; depression; exercise; Genetics; Mental depression; Neurobiology; Polymorphism; Risk factors; Veterans
• ISSN: 1064-7481; 1545-7214
• DOI: 10.1016/j.jagp.2020.02.001

•Using data from a nationally representative sample of older U.S. military veterans, we examined the direct and interactive effects of depression, brain-derived neurotropic factor (BDNF) Val66Met genotype, and physical exercise on cognitive functioning.•Depression is associated with moderate decrements in cognitive functioning in older U.S. military veterans. This association is moderated by BDNF Val66Met genotype and physical exercise, with Met allele carriers and nonexercisers performing worse on cognitive measures relative to Val/Val homozygotes and exercisers.•The detrimental effect of depression on cognitive functioning is moderated by two factors known to alter BDNF function the brain—BDNF Val66Met genotype and physical exercise. Depression is associated with increased risk for cognitive dysfunction, yet little is known about genetic and behavioral factors that may moderate this association. Using data from a nationally representative sample of older U.S. military veterans, we examined the direct and interactive effects of depression, brain-derived neurotropic factor (BDNF) Val66Met genotype, and physical exercise on cognitive functioning. One thousand three hundred eighty-six older European-American U.S. military veterans (mean age = 63) completed a web-based survey and cognitive assessment. Analyses of covariance were conducted to evaluate the effects of depression, BDNF Met allele carrier status, and physical exercise on these measures. Depressed veterans scored worse than nondepressed veterans on subjective measures of cognitive functioning (Cohen d's = 0.34–0.57) and objective measures of visual learning (d = 0.39) and working memory (d = 0.28). Among depressed veterans, those who were Met allele carriers scored worse than Val/Val homozygotes on subjective cognitive measures (d's = 0.52–0.97) and an objective measure of visual learning (d = 0.36). Engagement in physical exercise moderated the association between depression and cognitive function, with depressed exercisers scoring better than depressed nonexercisers on a subjective measure of reasoning, and objective measures of processing speed, attention, and visual learning (d = 0.58–0.99): further, in depressed Met allele carriers, exercisers scored better than nonexercisers on subjective cognitive (d's = 0.80–1.92), and objective measures of visual learning (d = 0.8–1.31) and working memory (d = 0.67). Depression is associated with moderate decrements in cognitive functioning in older U.S. m