Accelerated Brain Atrophy in Epilepsy: A Prospective Population‐Based Study

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OBJECTIVE: Previous longitudinal neuroimaging studies suggest that epilepsy is a progressive disorder. To date, these findings have relied largely on populations from tertiary centers, resulting in ascertainment bias, as severely affected individuals are more likely to be rescanned. We aimed to determine rates of progressive brain atrophy in a prospective, population-based cohort. METHODS: We analyzed longitudinal magnetic resonance imaging (MRI) data from 116 individuals with epilepsy and 89 age- and sex-matched healthy controls recruited from a prospective, longitudinal, community-based cohort in the United Kingdom. All participants underwent 2 scans 3.5 years apart, regardless of seizure status. We quantified progressive changes in cortical thickness and subcortical volumes using state-of-the-art longitudinal morphometry. RESULTS: People with epilepsy exhibited accelerated but modest global grey matter volume (GMV) loss compared with controls (2.7 vs 2.4 ml/year; p = 0.01). This acceleration was associated with specific phenotypes: focal epilepsy, MRI-identifiable lesions, and ongoing seizures. In contrast, generalized epilepsy and seizure-free periods were associated with more stable global trajectories. Cortical regions identified as vulnerable were characterized by markedly accelerated thinning compared to controls (5.3 vs 3.4 μm/year; p < 0.001) and were pervasive across most epilepsy phenotypes. INTERPRETATION: Epilepsy is associated with progressive structural brain damage that exceeds normal aging, but the trajectory is heterogeneous. These prospective population-based data confirm that vulnerable regions show progressive atrophy, particularly in focal and lesional epilepsy and individuals with ongoing seizures. ANN NEUROL 2026.

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