Effects of Sarcopenia and Frailty on Cognitive Function, Brain Volume, and Dementia Risk: A Prospective Cohort Study Based on UK Biobank

Abstract

Background and Purpose: Despite the rising prevalence of sarcopenia, frailty, and dementia, their interrelationships remain unclear. This study investigated the associations of sarcopenia and frailty with cognitive function, brain structure, incident dementia, and their longitudinal changes. Methods: This study included 390,903 participants aged 40–70 years from the UK Biobank. Sarcopenia was assessed using hand grip strength, muscle mass index, and gait speed; frailty was measured based on weight loss, exhaustion, physical activity, gait speed, and grip strength. Outcomes included cognitive test scores, magnetic resonance imaging-derived brain volumes, and incident dementia. Linear regression, Cox proportional hazards models, and linear mixed effects models were used. Results: Frailty was associated with poorer performance across cognitive domains (all p<0.05), while sarcopenia was associated with slower reaction time (p<0.001). Frailty, but not sarcopenia, was associated with reduced cortical volume. Both conditions increased all-cause dementia risk: frailty with a dose-response gradient (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.87 to 2.38) and particularly strong associations with vascular dementia (VaD, HR, 2.39; 95% CI, 1.85 to 3.07); sarcopenia with a moderate increase (HR, 1.53; 95% CI, 1.09 to 2.12). Longitudinally, sarcopenia—but not frailty—was associated with accelerated cognitive decline. Conclusions: Sarcopenia and frailty show overlapping but non-identical patterns of association with neurocognitive outcomes: sarcopenia was linked to longitudinal cognitive decline, whereas frailty was associated with cortical volume reduction and VaD. Early identification of these conditions is crucial for mitigating neurodegenerative decline and reducing dementia risk.