The brain-derived neurotrophic factor Val66Met polymorphism moderates an effect of physical activity on working memory performance

Abstract

Physical activity enhances cognitive performance, yet individual variability in its effectiveness limits its widespread therapeutic application. Genetic differences might be one source of this variation. For example, carriers of the methionine-specifying (Met) allele of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism have reduced secretion of BDNF and poorer memory, yet physical activity increases BDNF levels. To determine whether the BDNF polymorphism moderated an association of physical activity with cognitive functioning among 1,032 midlife volunteers (mean age = 44.59 years), we evaluated participants' performance on a battery of tests assessing memory, learning, and executive processes, and evaluated their physical activity with the Paffenbarger Physical Activity Questionnaire. BDNF genotype interacted robustly with physical activity to affect working memory, but not other areas of cognitive functioning. In particular, greater levels of physical activity offset a deleterious effect of the Met allele on working memory performance. These findings suggest that physical activity can modulate domain-specific genetic (BDNF) effects on cognition.

Keywords: BDNF; episodic memory; executive function; genetics; physical activity; visual memory; working memory.

Fig. 1

Results showing the effects of physical activity (weekly kilocalories expended) and the brain-derived neurotrophic factor (BDNF) polymorphism on four factors of cognitive performance: (a) working memory, (b) episodic memory, (c) switching, and (d) visuo-spatial memory. Physical activity was determined using the energy-expenditure metric from the Paffenbarger Physical Activity Questionnaire (Paffenbarger, Wing, & Hyde, 1978). Val = valine-specifying allele; Met = methionine-specifying allele.

Fig. 2

Results showing the effects of physical activity (weekly kilocalories expended) and the brain-derived neurotrophic factor (BDNF) polymorphism on four factors of working memory performance: accuracy on (a) the letter 1-back test, (b) the letter 3-back test, (c) the spatial 1-back test, and (d) the spatial 2-back test. Each working memory test consisted of 56 trials (50% match, 50% nonmatch). Physical activity was determined using the energy-expenditure metric from the Paffenbarger Physical Activity questionnaire (Paffenbarger, Wing, & Hyde, 1978). Val = valine-specifying allele; Met = methionine-specifying allele.