Associations of cardiorespiratory fitness and exercise with brain white matter in healthy adults: A systematic review and meta-analysis

Magnetic resonance imaging (MRI) studies have revealed positive associations between brain structure and physical activity, cardiorespiratory fitness, and exercise (referred to here as PACE). While a considerable body of research has investigated the effects of PACE on grey matter, much less is known about effects on white matter (WM). Hence, we conducted a systematic review of peer-reviewed literature published prior to 5^th July 2021 using online databases (PubMed and Scopus) and PRISMA guidelines to synthesise what is currently known about the relationship between PACE and WM in healthy adults. A total of 60 studies met inclusion criteria and were included in the review. Heterogeneity across studies was calculated using Qochran’s q test, and publication bias was assessed for each meta-analysis using Begg and Mazumdar rank correlation test. A meta-regression was also conducted to explore factors contributing to any observed heterogeneity. Overall, we observed evidence of positive associations between PACE and global WM volume (effect size (Hedges’s g) = 0.137, p < 0.001), global WM anomalies (effect size = 0.182, p < 0.001), and local microstructure integrity (i.e., corpus callosum: effect size = 0.345, p < 0.001, and anterior limb of internal capsule: effect size = 0.198, p < 0.001). These findings suggest that higher levels of PACE are associated with improved global WM volume and local integrity. We appraise the quality of evidence, and discuss the implications of these findings for the preservation of WM across the lifespan. We conclude by providing recommendations for future research in order to advance our understanding of the specific PACE parameters and neurobiological mechanisms underlying these effects.