•Structural brain networks were derived from 3T diffusion MRI images using Brain Connectivity Toolbox (MATLAB; 94 brain regions = nodes) (5)

•Analyses were performed using linear regression models adjusted for age, sex, education, smoking, alcohol intake, and technical MRI covariates (model 1);  and additionally for cardiometabolic health* (model 2)

•Higher CRF was associated with greater whole-brain node degree and PFC node degree; both associations were attenuated after adjusting for cardiometabolic factors in model 2 (Table 1)

•No significant associations of CRF with local or global efficiency

•CRF × age interactions indicated stronger associations of CRF with whole-brain node degree and with local efficiency at older ages; models with additional CRF × age² terms improved fit but attenuated all CRF-by-age interaction effects (Figure 1)

•Associations of CRF with greater WM connection count (node degree) – aligned with previous CRF–WM integrity findings (6, 7).

•Attenuation of CRF–node degree associations by cardiometabolic factors (especially type 2 diabetes status) suggests possible mediating role of cardiometabolic health (CRF → cardiometabolic health → WM connectivity). However, the reverse cannot be excluded (e.g., higher cardiometabolic health causing both higher CRF and better WM connectivity).

•Age-dependent patterns aligns with the hypothesis of putative CRF benefits for brain health strengthening with age (1, 6, 7). This could be because age-related declines in WM health renders the brain more responsive to CRF-related neuroprotective processes.

•No associations of CRF with network efficiency contrasts with a previous study reporting CRF–efficiency associations (8), likely reflecting differences in efficiency metric definitions and calculations.

•Our findings hint that CRF may help preserve WM connection count, especially in older age (approx. >70 years), possibly in part via cardiometabolic pathways.

•Findings broadly align with previous research linking CRF to brain health in older age.

•Longitudinal and intervention studies are needed to confirm and further explore these patterns.

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6.Hayes, S. M., et al. (2015). Cardiorespiratory fitness is associated with white matter integrity in aging. Ann Clin Transl Neurol, 2(6), 688–698.

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