High-intensity Exercise and Cognitive Function in Cognitively Normal Older Adults: A Randomised Clinical Trial

BACKGROUND: Physical inactivity has been consistently linked to increased risk of cognitive decline; however, studies examining the impact of exercise interventions on cognition have produced inconsistent findings. Some observational studies suggest exercise intensity may be important for inducing cognitive improvements; however, this has yet to be thoroughly examined in older adult cohorts. The objective of the current study was to evaluate the effect of systematically manipulated high-intensity and moderate-intensity exercise interventions on cognition. In addition, we investigated individual variability in exercise response by examining effects of relevant genetic factors and changes in cardiorespiratory fitness on cognitive change.METHODS: This multi-arm randomised clinical trial investigated the effects of 6-months of high-intensity exercise and moderate-intensity exercise, compared with an inactive control, on cognition. Outcome measures were assessed at pre- (baseline), post- (6 months), and 12-months post-intervention. Ninety-nine cognitively normal men and women (aged 60 – 80 years) were enrolled from October 2016 to November 2017. Participants that were allocated to an exercise group (i.e., high-intensity or moderate-intensity) engaged in cycle-based exercise two times per week for 6 months. Cognition was assessed using a comprehensive neuropsychological test battery. Cardiorespiratory fitness was evaluated by a graded exercise test. Apolipoprotein e4 genotype and brain-derived neurotrophic factor Val66Met carriage were identified.RESULTS: There was a dose-dependent effect of exercise intensity on cardiorespiratory fitness; whereby the high-intensity group experienced greater increases in fitness than the moderate-intensity and control groups. However, there was no direct effect of exercise on cognition. We observed an association between changes in global cognition and executive function and changes in cardiorespiratory fitness from pre- to post-intervention: this relationship was strongest in brain-derived neurotrophic factor non-Met carriers.CONCLUSIONS We did not observe a direct effect of exercise on cognition. Nevertheless, our data suggests genetics may moderate the relationship between fitness and cognitive change following exercise, and this should be examined further in larger trials.TRIAL REGISTRATION: This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000643370). Registered 3rd May 2017 - retrospectively registered. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372780