Epilepsy is associated with the accelerated aging of brain activity in sleep

Objective: Although seizures are the cardinal feature, epilepsy is associated with other forms of brain dysfunction including impaired cognition, abnormal sleep, and increased risk of developing dementia. We hypothesized that, given the widespread neurologic dysfunction caused by epilepsy, accelerated brain aging would be seen. We measured the sleep-based brain age index (BAI) in a diverse group of patients with epilepsy. The BAI is a machine learning-based biomarker that measures how much the brain activity of a person during overnight sleep deviates from chronological age-based norms.

Methods: This case-control study drew information of age-matched controls without epilepsy from home sleep monitoring volunteers and from non-epilepsy patients with Sleep Lab testing. Patients with epilepsy underwent in-patient monitoring and were classified by epilepsy type and seizure burden. The primary outcomes measured were BAI, processed from electroencephalograms, and epilepsy severity metrics (years with epilepsy, seizure frequency standardized by year, and seizure burden [number of seizures in life]). Subanalyses were conducted on a subset with NIH Toolbox cognitive testing for total, fluid, and crystallized composite cognition.

Results: 138 patients with epilepsy (32 exclusively focal and 106 generalizable [focal seizures with secondary generalization]) underwent in-patient monitoring, and age-matched, non-epilepsy controls were analyzed. The mean BAI was higher in epilepsy patients vs controls and differed by epilepsy type: -0.05 years (controls) versus 5.02 years (all epilepsy, p < 0.001), 5.53 years (generalizable, p < 0.001), and 3.34 years (focal, p = 0.03). Sleep architecture was disrupted in epilepsy, especially in generalizable epilepsy. A higher BAI was positively associated with increased lifetime seizure burden in focal and generalizable epilepsies and associated with lower crystallized cognition. Lifetime seizure burden was inversely correlated with fluid, crystallized, and composite cognition.

Significance: Epilepsy is associated with accelerated brain aging. Higher brain age indices are associated with poorer cognition and more severe epilepsy, specifically generalizability and higher seizure burden. These findings strengthen the use of the sleep-derived, electroencephalography-based BAI as a biomarker for cognitive dysfunction in epilepsy.