Late-onset unexplained epilepsy: What are we missing?

With the aging of the US population, the incidence of epilepsy will increase, with 25 to 50% of new cases with no identifiable etiology diagnosed as late-onset unexplained epilepsy (LOUE). In the current targeted review, we discuss the possible role of cerebral small vessel ischemic disease, accumulation of amyloidβ and hyperphosphorylated tau, and sleep apnea as potential pathophysiologic mechanisms explaining LOUE. We highlight the impact of these processes on cognition and avenues for diagnosis and treatment.