Grey and White Matter Pathways Underlying the Relationship Between Aerobically Active Lifestyle, Cardiorespiratory Function, and Episodic Memory in the Aging Human Brain

Aging is associated with structural alterations of the hippocampus, a key region in episodic memory processes. Aerobic activity and maximal aerobic capacity (MAC), a key measure of cardiorespiratory function and a physiological adaptation of aerobic exercise, have been associated with biological and cognitive resilience of the brain. However, investigations of their relationship with the hippocampus in humans had resulted with inconsistent findings. This study aimed to investigate the relationship between lifestyles aerobic activity and MAC and hippocampal grey and white matter structure, as well as episodic memory performance in cognitively healthy older adults. In addition, we examined the relationship between aerobic activity and MAC, and cerebrovascular pathology expressed as white matter lesions (WML). Next, we used a regression-based mediation analysis to examine possible biological pathways which may underlie the relationship between MAC and hippocampal volume, which was demonstrated in previous works, and was confirmed in the current study. Fifty cognitively healthy older adults (70.92 {+/-} 3.9 years) were divided into aerobically active (n=27) and non-active (n=23) groups, and performed structural and diffusion MRI. Forty-two participants were also evaluated for MAC. Aerobically active lifestyle and higher MAC were associated with increased hippocampal volume and microstructural integrity, as well as increased fornix microstructural integrity, and lower WML burden (p<.05). In addition, both factors were correlated with increased episodic memory performance (p<.05). Mediation analysis revealed two pathways potentially mediating the relationship between MAC, hippocampal volume, and episodic memory - a white matter pathway consisted of WML and fornix microstructure, and grey matter pathway including hippocampal microstructure. These findings shed light on possible neurobiological mechanisms that could potentially underlie the neuroprotective effect of cardiorespiratory function and aerobic physical activity on hippocampal macrostructure and memory function in the aging human brain.