Abstract
BACKGROUND: Epilepsy, as a chronic noncommunicable disease with recurrent seizures, may be a marker of deterioration or alteration in other underlying neurological diseases. This study aimed to investigate the relationship of epilepsy with brain function, other common brain disorders, and their underlying mechanisms. METHODS: The study was based on clinical diagnostic and test data from 426,527 participants in the UK Biobank, of whom 3,251 were diagnosed with epilepsy at baseline. Multiple linear and Cox regression models were used to explore the association between epilepsy, brain function, and other brain disorders. RESULTS: This study demonstrated consistent deleterious effects of epilepsy on cognitive and motor function and mental health. The risk of neurological diseases and psychiatric disorders was significantly elevated in the epilepsy population during the 17-year follow-up period, according to the longitudinal analysis. We also identified several brain regions associated with epilepsy, including the pallidum, hippocampus, and precentral regions. Mediation analyses revealed mediating effects of peripheral markers and proteins (e.g., GGT, HDL, ACE2, and GDF15), suggesting that liver function and lipid metabolism may be involved in the development of other brain disorders in individuals with epilepsy. CONCLUSIONS: Our study provides robust evidence of the association between epilepsy and poor brain health, underscoring the importance of early intervention for epilepsy.