Sarcopenic obesity and dementia risk: Primary associations and landmark analyses of muscle strength and body composition trajectories

Guan Z.; Stephan B.C.; Donini L.M.; Godos J.; Grosso G.; Pereira L.R.; Prado C.M.; Toro-Huamanchumo C.J.; Wells J.C.; Sim M.; Siervo M. · Clinical Nutrition (2026) · DOI: 10.1016/j.clnu.2026.106696

Resumen

Background and aims: Sarcopenic obesity (SO) has been proposed as a risk factor for cognitive impairment. Yet evidence is inconsistent and often limited by heterogeneous definitions and lack of longitudinal assessments. This study aimed to examine associations of SO with all-cause and subtype-specific dementia, and to assess dose–response patterns and how longitudinal changes in body composition and muscle strength relate to dementia risk. Methods: We included 489,972 adults (mean age 56.5 ± 8.1 years) followed for a median of 13.6 years. SO was defined using the Sarcopenic Obesity Global Leadership Initiative (SOGLI) criteria. Cox models estimated hazard ratios (HRs) for all-cause dementia, Alzheimer's disease (AD), and vascular dementia. Restricted cubic spline (RCS) analysis assessed dose–response associations. Landmark analyses among 54,070 participants (median follow-up 4.1 years) evaluated how longitudinal changes in handgrip strength (HGS) and body composition related to subsequent dementia risk. Results: SO (HR = 1.34; 95% CI: 1.18–1.52) and sarcopenia (HR = 1.30; 95% CI: 1.14–1.48) were associated with higher all-cause dementia risk compared with the non-sarcopenic, non-obesity group, whereas obesity alone was associated with lower risk (HR = 0.91; 95% CI: 0.84–0.99). Age and sex modified these associations, with stronger associations observed among adults younger than 65 years and more pronounced risk elevations for sarcopenia (HR = 1.37; 95% CI: 1.07–1.75) and SO (HR = 1.55; 95% CI: 1.29–1.87) in males, whereas obesity showed inverse associations with dementia risk primarily in females (HR = 0.81; 95% CI: 0.71–0.92). RCS analyses showed J-shaped associations between fat mass percentage (%FM) and dementia risk in males, lower dementia risk at higher levels of %FM in older females, and strong inverse associations between HGS and dementia risk in both sexes. Landmark analyses showed that declines in HGS consistently predicted all-cause dementia. Conclusion: SO and sarcopenia are associated with dementia risk. HGS is a significant predictor of dementia risk supporting the inclusion of measures of muscle function in dementia prevention strategies.

Instituciones: Universidad San Ignacio de Loyola