Association Between Body Composition Patterns, Brain Diseases and Injuries and Risk of Epilepsy: a Prospective Cohort Study

Aims: Different body compositions may exert varying effects on epilepsy. We aimed to prospectively examine the associations between body composition patterns, specific measurements and epilepsy risk, while exploring the mediating role of brain-related injuries. Methods: We constructed a large-scale cohort study within the UK Biobank (UKB), deriving 7 body composition patterns via principal component analysis (PCA) that captured variation in muscle strength, bone density, lean mass and fat distribution. Multivariable Cox proportional hazards models were employed to assess associations between these patterns, individual body measurements and epilepsy risk. We performed stratified analyses by polygenic risk score (PRS) and mediation analyses to evaluate the indirect contributions of brain injuries. Results: Among the 475,960 participants, 3,026 epilepsy cases were identified over an average follow-up of 10.9 years. Patterns of “lean mass”, “muscle strength”, “bone density” and “leg-dominant fat distribution” were associated with reduced risk of epilepsy (hazard ratios [HRs]: 0.68-0.97), whereas “fat-to-lean mass”, “central obesity” and “arm-dominant fat distribution” patterns were associated with increased incidence (HRs: 1.01-1.34). Similar trends were noted for corresponding individual body measurements. These associations were consistent across PRS strata. Falls, stroke, and neurodegenerative diseases mediated 17.9%, 27.2%, and 31.0% of effects for “muscle strength,” “bone density,” and “arm-dominant fat distribution”, respectively. Conclusions: Body composition patterns involving muscle strength, bone density, and fat distribution show robust associations with epilepsy, partly mediated by neurological disorders. Optimizing body composition and preventing neurological insults may help reduce epilepsy risk in middle-aged and older adults.