1. Physical frailty, particularly slow gait speed, was independently associated with a significantly increased risk of incident epilepsy in a large longitudinal cohort.
Evidence Rating Level: 2 (Good)
In this large prospective cohort study, Hu et al. investigated the association between physical frailty and incident epilepsy using data from 421,383 participants in the UK Biobank who were free of epilepsy and major neurologic disease at baseline. Physical frailty was assessed using a modified Fried frailty phenotype consisting of weight loss, exhaustion, low physical activity, slow gait speed, and low grip strength. Participants were categorized as non-frail, pre-frail, or frail and followed for a mean of 13.2 years for the development of epilepsy identified through linked health records. During follow-up, 2,752 incident epilepsy cases were identified. After adjustment for sociodemographic, lifestyle, and medical factors, prefrailty and frailty were independently associated with increased epilepsy risk, with hazard ratios of 1.29 and 1.81, respectively, compared with non-frail individuals. A dose-response relationship was observed between increasing frailty severity and epilepsy incidence. Among frailty components, slow gait speed demonstrated the strongest association with epilepsy risk. Biomarker analyses suggested that inflammatory, metabolic, endocrine, renal, hepatic, and hematologic pathways may partially mediate the frailty-epilepsy relationship, collectively explaining approximately 18.6% of the observed association. The authors conclude that physical frailty is an independent predictor of incident epilepsy and may represent a potentially modifiable target for epilepsy prevention in older adults.
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