The impact of age, sex, and genetics on the relationship between objectively measured habitual physical activity and brain volume: A cross‐sectional UK Biobank study

Background Grey matter atrophy occurs as a function of ageing and is accelerated in neurodegenerative conditions, such as dementia. Previous research suggests higher physical activity is associated with larger grey matter volumes; however, there appears to be individual variability in this association. Understanding factors that can affect the relationship between physical activity and brain volume will enable identification of individuals that gain the greatest neural benefits from physical activity. Method Data from 10,084 men and women (aged 50+ years) of the UK Biobank were used to examine: 1) the relationship between actigraphy‐measured habitual physical activity and brain volume; and 2) whether the relationship between objectively‐measured physical activity and brain volume is moderated by age, sex, BDNF Val66Met, or APOE ε4 allele carriage. All participants underwent a magnetic resonance imaging scan to quantify grey matter volumes, activity monitoring, and genotyping. Result Physical activity was associated with larger total grey matter volume (B = 0.14, p = 0.001) and right hippocampal volume (B = 1.45, p = 0.008). The physical activity*sex interaction was significant for cortical grey matter (B = 0.22, p = 0.003), total grey matter (B = 0.30, p < 0.001), and right hippocampal volume (B = 3.62, p = 0.001). A relationship between physical activity and brain volume was observed in males only (cortical grey matter volume, B= 0.13, p = 0.01; total grey matter volume, B=0.23, p < 0.001; and right hippocampal volume, B = 2.29, p = 0.008). No other moderating factors of the physical activity and brain volume relationship were identified. Conclusion Our results indicate that in males, but not females, an association exists between habitual physical activity and brain volume. Future research should evaluate longitudinal brain volumetrics to better understand the nature of sex‐effects on the relationship between physical activity and brain volume.