Leveraging the extensive and multilayered population-based data to systematically elucidate the relationship between physical frailty and brain health.

Here, 316905 participants from the UK Biobank were included in this prospective longitudinal study. Physical frailty was assessed by five phenotypes, including exhaustion, low grip strength, low physical activity, weight loss, and slow walking speed. Linear regression model and cross-lagged panel model were firstly applied to evaluate the cross-sectional and longitudinal relationship of physical frailty with brain function, including mental health and cognitive function. Cox proportional hazard model and Mendelian randomization analyses were further conducted to examine the longitudinal association and causal relationship between physical frailty and eight brain disorders. Finally, the cross-sectional correlation between physical frailty and brain cortical and subcortical regions were assessed using linear regression model.