Acute exercise-induced increases in brain-derived neurotrophic factor in plasma relates to subsequent learning in older adults: A randomized controlled intervention trial

Multidomain lifestyle interventions have been identified as a promising strategy to counteract cognitive decline in older age but mechanistic accounts for how such interventions should be designed are lacking. Brain-derived neurotrophic factor is essential for experience-dependent plasticity and increases transiently following physical exercise, suggesting that physical exercise may facilitate subsequent learning by inducing a heightened state of brain plasticity. We therefore hypothesized that cognitive ability in older adults would benefit more from cognitive training when it is immediately preceded as opposed to followed by physical exercise and that the relationship between exercise-induced increases in peripheral BDNF (assessed at pretest) and cognitive training outcomes (change from pretest to posttest) would be greater when cognitive training is preceded by physical exercise. Healthy older adults (n=97) were randomized to receive either physical exercise immediately before cognitive training, physical exercise immediately after cognitive training, physical exercise only, or cognitive training only, in each training session during a 12-week long intervention period. Consistent with the hypothesis, greater increases of plasma BDNF following physical exercise were associated with greater cognitive training gains on trained task paradigms, but only when such increases immediately preceded cognitive training (ß=0.14, 95% CI [0.04, 0.25]). However, average cognitive training outcome did not significantly differ depending on whether participants received physical exercise before or after cognitive training (ß=0.05, 95% CI [-0.10, 0.20]). The study provides the first empirical support for a time-critical but advantageous role for post-exercise increases in peripheral BDNF for learning in older adults at an interindividual level, with implications for the design of future multidomain interventions. More research will be required to understand the factors that likely interact with and counteract such beneficial effects and to determine whether all older adults could potentially benefit from engaging in physical exercise prior to learning.