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Purpose  To determine the impact of childhood‐onset uncomplicated epilepsy (COE) on brain aging over 50‐year prospective follow‐up.    Methods  A population‐based cohort of 41 aging subjects with COE and their 46 matched controls participated in a detailed in‐person prospective assessment in 2012 and 2017 to characterize ongoing changes in the aging brain.    Results  The mean age of the COE participants was 63.2 years (SD 4.14, median 63.2, range 55.8–70.6) and 63.0 years (mean, SD 4.13, median 63.3, range 56.0–69.9) years for controls. Neurologic signs were significantly more common in COE participants not in remission ( p  = .015), and the most frequent abnormalities were cerebellar signs ( p  < .001). Neurologic signs in general ( p  = .008) and cerebellar signs in particular ( p  = .018) were significantly more common in focal than in generalized epilepsies. MRI white matter abnormalities were significantly associated with absence of vocational education ( p  = .011), and MRI hippocampal atrophy in COE subjects was associated with arterial hypertension versus normal blood pressure ( p  = .017). In the combined study cohort of COE subjects and controls, presenting neurologic signs increased both in the subjects and in the controls from the 2012 to 2017 study.    Conclusions  At ultra‐long‐term follow‐up, clinical and neuroimaging findings show tendencies to brain aging that is more accelerated in COE participants with active adult childhood‐onset epilepsy, and particularly in focal epilepsy.

Differences in brain changes between adults with childhood‐onset epilepsy and controls: A prospective population‐based study