Non-Modifiable Factors as Moderators of the Relationship Between Physical Activity and Brain Volume: A Cross-Sectional UK Biobank Study

Article type: Research Article

Authors: Brown, Belinda M.^{a; b; c; *} | de Frutos Lucas, Jaisalmer^{c; d} | Porter, Tenielle^{c; e; f} | Frost, Natalie^a | Vacher, Michael^g | Peiffer, Jeremiah J.^a | Laws, Simon M.^{c; e; f}

Affiliations: [a] Centre for Healthy Ageing, Health Futures Institute, Murdoch University, Murdoch, WA, Australia | [b] Australian Alzheimer’s Research Foundation, Sarich Neuroscience Research Institute, Nedlands, WA, Australia | [c] Centre for Precision Health, Edith Cowan University, Joondalup, WA, Australia | [d] Experimental Psychology, Cognitive Processes and Logopedia Department, School of Psychology, Universidad Complutense de Madrid, Pozuelo de Alarcón, Spain | [e] Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia | [f] School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA, Australia | [g] Australian e-Health Research Centre, CSIRO, Floreat, WA, Australia

Correspondence: [*] Correspondence to: Belinda Brown, PhD, Murdoch University, 90 South Street, Murdoch, WA, Australia. Tel.: +61 8 9360 6193; E-mail: b.brown@murdoch.edu.au.

Abstract: Background:Previous research suggests physical activity attenuates grey and white matter loss; however, there appears to be individual variability in this effect. Understanding factors that can influence the relationship between physical activity and brain volume may enable prediction of individual response. Objective:The current study examined the relationship between objectively-measured physical activity and brain volume; and whether this relationship is moderated by age, sex, or a priori candidate genetic factors, brain-derived neurotrophic factor (BDNF) Val66Met, or apolipoprotein (APOE) ɛ4 allele carriage. Methods:Data from 10,083 men and women (50 years and over) of the UK Biobank were used to examine the study objectives. All participants underwent a magnetic resonance imaging scan to quantify grey and white matter volumes, physical activity monitoring via actigraphy, and genotyping. Results:Physical activity was associated with total grey matter volume, total white matter volume, and right hippocampal volume. Only males had an association between higher physical activity levels and greater cortical grey matter volume, total grey matter volume, and right hippocampal volume. Age moderated the relationship between physical activity and white matter volume. Conclusion:Our results indicate that in males, but not females, an association exists between objectively-measured physical activity and grey matter volume. Age may also play a role in impacting the relationship between physical activity and brain volume. Future research should evaluate longitudinal brain volumetrics to better understand the nature of age and sex-effects on the physical activity and brain volume relationship.

Keywords: Dementia, genotype, hippocampus, sex differences

DOI: 10.3233/JAD-220114

Journal: Journal of Alzheimer's Disease, vol. 88, no. 3, pp. 1091-1101, 2022