Associations of cardiorespiratory fitness with structural brain networks in ageing: insights from The Maastricht Study

Geroscience. 2026 Jun 6. doi: 10.1007/s11357-026-02329-1. Online ahead of print.

ABSTRACT

Higher cardiorespiratory fitness (CRF) has been linked to healthier brain ageing, which includes preservation of white matter (WM) tracts. However, whether CRF might help preserve whole-brain WM networks and whether this varies with age remains unclear. To address this gap, we used cross-sectional data from The Maastricht Study (N = 4432, mean age 59.2 ± 8.7 years, range 40-79, 51% female). We derived CRF estimates from submaximal ergometry (VO₂-max) and WM network metrics (whole-brain node degree [connection count], prefrontal cortex [PFC] node degree, global efficiency, local efficiency) from 3T MRI. Associations of CRF with WM network metrics were assessed using linear regressions adjusted for age, sex, education, smoking, alcohol intake, MRI covariates (model 1), and additionally for cardiometabolic health metrics (model 2). CRF-by-age and CRF-by-age² interaction terms tested whether CRF-WM network associations vary linearly or non-linearly with age. Results showed that higher CRF was associated with greater whole-brain and PFC node degree in model 1; however, associations attenuated after accounting for cardiometabolic health (e.g., whole-brain node degree, model 1: β = 0.053, 95% CI [0.020, 0.085], p = 0.001; model 2: β = 0.024, 95% CI [-0.014, 0.061], p = 0.224). Further, significant CRF-by-age interactions in model 2 indicated stronger associations of CRF with whole-brain node degree and local efficiency at older ages. Adding quadratic interactions (CRF-by-age + CRF-by-age²) improved model fit and hinted at CRF-WM connectivity associations only in the oldest group (CRF-by-age² for whole-brain node degree: β = 0.027, 95% CI [0.002, 0.052], p = 0.038). Our findings add to mounting evidence linking higher CRF to brain health in older age.

PMID:42250113 | DOI:10.1007/s11357-026-02329-1