Physical activity levels and brain structure in middle-aged and older adults: a bidirectional longitudinal population-based study

Physical activity has been suggested as modifiable factor that might contribute to improving cognitive and brain function during aging. However, previous studies were mainly of cross-sectional design and did not consider effects of time or potential reverse causality. We aimed to investigate the bidirectional associations of physical activity with brain structure in middle-aged and older adults. Overall, 4365 par-ticipants (64.01 +/- 10.82 years; 56% women) from the Rotterdam Study had physical activity and brain structure assessed on at least one of 2 timepoints ('baseline': 2006-2012 or 'follow-up': 2012-2017, me-dian 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 bidi-rectional associations, and linear mixed-effects models to investigate the consistency of findings. Larger total brain volume (fi = 0.067, 95%-confidence interval 0.035;0.099, pFDR = 0.001), gray matter volume (fi = 0.063, 0.031;0.096, pFDR = 0.002), and white matter volume (fi = 0.051, 0.020;0.083, pFDR = 0.013) at baseline were associated with higher levels of sports at follow-up. Lower global mean diffusivity at base-line was associated with higher levels of walking at follow-up (fi =-0.074,-0.111;-0.037, pFDR = 0.001). No associations were found between physical activity levels at baseline and brain metrics at follow-up. In conclusion, larger brain volumes and white matter microstructure at baseline were associated with individuals remaining more physically active at follow-up. Overall, this study identified older adults with potentially advanced brain aging status as being at higher risk of physical inactivity over time, and there-fore as potential target group for prevention and novel intervention strategies.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

The study found bidirectional associations between physical activity and brain structure in middle-aged and older adults. Larger brain volumes and white matter microstructure at baseline were associated with higher levels of physical activity at follow-up. Additionally, lower baseline global mean diffusivity was associated with higher levels of walking at follow-up.