Background and Objectives Late-onset epilepsy (LOE; i.e., epilepsy starting in later adulthood) affects a significant number of individuals. Head injury is also a risk factor for acquired epilepsy, but the degree to which prior head injury may contribute to LOE is less well understood. Our objective was to determine the association between head injury and subsequent development of LOE. Methods Included were 8,872 participants enrolled in the Atherosclerosis Risk in Communities (ARIC) study with continuous Centers for Medicare Services fee-for-service (FFS) coverage (55.1% women, 21.6% Black). We identified head injuries through 2018 from linked Medicare fee for service claims for inpatient/emergency department care, active surveillance of hospitalizations, and participant self-report. LOE cases through 2018 were identified from linked Medicare FFS claims. We used Cox proportional hazards models to evaluate associations of head injury with LOE, adjusting for demographic, cardiovascular, and lifestyle factors. Results The adjusted hazard ratio (HR) for developing LOE after a history of head injury was 1.88 (95% confidence interval [CI] 1.44-2.43). There was evidence for dose-response associations with greater risk for LOE with increasing number of prior head injuries (HR 1.37, 95% CI 1.01-1.88 for 1 prior head injury and HR 3.55, 95% CI 2.51-5.02 for 2+ prior head injuries, compared to no head injuries) and with more severe head injury (HR 2.53, 95% CI 1.83-3.49 for mild injury and HR 4.90, 95% CI 3.15-7.64 for moderate/severe injury, compared to no head injuries). Associations with LOE were significant for head injuries sustained at older age (age ≥67 years: HR 4.01, 95% CI 2.91-5.54), but not for head injuries sustained at younger age (age < 67 years: HR 0.98, 95% CI 0.68-1.41). Discussion Head injury was associated with increased risk of developing LOE, particularly when head injuries were sustained at an older age, and there was evidence for higher risk for LOE after a greater number of prior head injuries and after more severe head injuries. Classification of Evidence This study provides Class I evidence that an increased risk of late-onset epilepsy is associated with head injury and that this risk increases further with multiple and more severe head injuries
