Biological Sex: A Potential Moderator of Physical Activity Efficacy on Brain Health

Abstract

The number of older people worldwide living with cognitive impairment and neurodegenerative diseases is growing at an unprecedented rate. Despite accumulating evidence that engaging in physical activity is a promising primary behavioral strategy to delay or avert the deleterious effects of aging on brain health, a large degree of variation exists in study findings. Thus, before physical activity and exercise can be prescribed as “medicine” for promoting brain health, it is imperative to understand how different biological factors can attenuate or amplify the effects of physical activity on cognition at the individual level. In this review article, we briefly discuss the current state of the literature, examining the relationship between physical activity and brain health in older adults and we present the argument that biological sex is a potent moderator of this relationship. Additionally, we highlight some of the potential neurobiological mechanisms underlying this sex difference for this relatively new and rapidly expanding line of research.

Exercise and Fitness Neuroprotective Effects: Molecular, Brain Volume and Psychological Correlates and Their Mediating Role in Healthy Late-Middle-Aged Women and Men

“…Therefore, differences in sex hormones that act as neurosteroids and interact with molecular growth factors, brain structures and cognition in a different manner for women and men could explain part of this variability (Ansdell et al, 2020 ). Besides, this is in accordance with recent bibliography stating sex differences in the association of exercise with brain and cognitive outcomes (Lindwall et al, 2008 ; Varma et al, 2015 , 2016 ; Barha et al, 2019 ; Dimech et al, 2019 ). Another potential explanation could be a dose-effect bias related to the described differences in the amount of physical activity performed by women and men.…”

“…One of our relevant results is that frequent exercise was related with greater temporal lobe volume in women and men, which is a key structure for memory and it deteriorates with aging. Moreover, consistent with Barha et al ( 2019 ), women that expended more energy in sportive physical activities had greater dorsolateral prefrontal cortex volume, which is involved in supporting executive functions, especially working memory. In other studies greater CRF levels have been linked to greater brain volumes (Raichlen et al, 2019 ; Wittfeld et al, 2020 ).…”

“…However, there is a poor understanding of the mediating role of these variables in the PA-cognition relationship and the multiple pathways by which microscopic and macroscopic biomarkers might influence each other to promote cognition are in current research. Identifying these pathways by which the benefits of exercise are realized is a challenge not only due to the multilevel mechanisms but also because of the role of factors that may moderate the association such as sex (Barha et al, 2019). Previous evidence suggests that both women and men might positively benefit cognition from exercise, although the CRFcognition relationship was only significant in men (Castells-Sánchez et al, 2020).…”

Dietary Anti-Aging Polyphenols and Potential Mechanisms

“…Substantial dietary intervention studies and epidemiological surveys have demonstrated that the consumption of a diet rich in fruits and vegetables has health-promoting effects [ 1 , 2 ]. It is estimated that the proportion of people aged 60 and above will increase from 12% in 2015 to 22% in 2050 [ 3 ]. Thus, delaying or preventing the onset of aging-related diseases due to cellular damage and functional decline would greatly improve life quality and expectancy, as well as mitigate the burden on the current healthcare system.…”

Optimal Human Functioning Requires Exercise Across the Lifespan: Mobility in a 1g Environment Is Intrinsic to the Integrity of Multiple Biological Systems

“…To achieve the above-mentioned goal will require more information and understanding regarding the mechanisms involved in responsiveness to exercise and better information regarding factors that modulate such responsiveness. There is clear evidence that sex can play a role in responsiveness to exercise at the level of the brain, with females responding more than males (reviewed in Barha et al, 2017Barha et al, , 2019Dao et al, 2019). This is an interesting response pattern since most Alzheimer patients are female.…”