Brain Structure and Physical Activity Levels in Middle-Aged and Elderly Individuals: A Bidirectional Longitudinal Population-Based Study

Abstract

Background: To prevent and reduce age-related brain changes, it is crucial to identify modifiable factors that might contribute to preserving brain health during aging. Therefore, we aimed to investigate the bidirectional associations of physical activity with brain structure in middle-aged and elderly individuals. Methods: Overall, 4,365 participants (64.01±10.82 years; 56% females) from the Rotterdam Study had physical activity and brain structure assessed on at least one of two timepoints (‘baseline’: 2006-2012 or ‘follow-up’: 2012-2017, median duration between visits: 5 years). Physical activity was assessed through the LASA Physical Activity Questionnaire. T1-weighted MRI and diffusion tensor imaging were used to quantify brain volumes and white matter microstructure, respectively. Cross-lagged panel models were performed to estimate bidirectional associations, and linear mixed-effects models to investigate the consistency of findings. False discovery rate (FDR) was used to correct for multiple testing. Findings: Larger total brain volume (β = 0.067, 95%CI 0.035;0.099, pFDR=0.001), gray matter volume (β= 0.063, 0.031;0.096, pFDR=0.002), and white matter volume (β= 0.051, 0.020;0.083, pFDR=0.013) were associated with an increase in sport participation over time. Lower global mean diffusivity was associated with an increase in walking levels over time (β= -0.074, -0.111;-0.037, pFDR=0.001). No associations were found between physical activity and changes in brain metrics over time. Interpretation: Physical activity was not associated with a healthier brain structure over time in elderly individuals. In contrast, brain structure was associated with individuals remaining physically active over time. Funding: Erasmus MC University Medical Center Rotterdam, and Netherlands Organization for the Health Research and Development. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The Rotterdam Study has been approved by the Medical Ethics Committee of Erasmus MC (registration number MEC 02.1015) and by the Dutch Ministry of Health, Welfare and Sport (Population Screening Act WBO, license number 1071272-159521-PG). The Rotterdam Study Personal Registration Data collection is filed with the Erasmus MC Data Protection Officer under registration number EMC1712001. Trial Registration: The Rotterdam Study has been registered at the Netherlands National Trial Register (NTR; www.trialregister.nl) and the WHO International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/network/primary/en/) under shared catalogue number NTR6831.