Structural brain changes in medically refractory focal epilepsy resemble premature brain aging

Objective We used whole brain T1-weighted MRI to estimate the age of individuals with medically refractory focal epilepsy, and compared with individuals with newly diagnosed focal epilepsy and healthy controls. The difference between neuroanatomical age and chronological age was compared between the three groups. Methods Neuroanatomical age was estimated using a machine learning-based method that was trained using structural MRI scans from a large independent healthy control sample (N = 2001). The prediction model was then used to estimate age from MRI scans obtained from newly diagnosed focal epilepsy patients (N = 42), medically refractory focal epilepsy patients (N = 94) and healthy controls (N = 74). Results Individuals with medically refractory epilepsy had a difference between predicted brain age and chronological age that was on average 4.5 years older than healthy controls (p = 4.6 × 10⁻⁵). No significant differences were observed in newly diagnosed focal epilepsy. Earlier age of onset was associated with an increased brain age difference in the medically refractory group (p = 0.034). Significance Medically refractory focal epilepsy is associated with structural brain changes that resemble premature brain aging.