Association Between Alzheimer Pathology, Sleep, and Cognition in Patients With Late-Onset Unexplained Epilepsy

BACKGROUND AND OBJECTIVES: Late-onset unexplained epilepsy (LOUE) has been linked to accelerated cognitive decline. However, the role of neurodegenerative proteins and whether they exert their effects through sleep-related mechanisms remain unexplored in this population. The goal of this study was to investigate the association of plasma p-tau217, a measure of Alzheimer disease (AD) pathology, with cognition in LOUE and its association with sleep. METHODS: Participants with LOUE, with new-onset unprovoked seizures, age at onset 55 years or older, and absence of cortical lesions on MRI, were prospectively recruited. They underwent cognitive testing which included the extended Preclinical Alzheimer Cognitive Composite (PACC5). A 24-hour EEG was obtained, and sleep manually scored. Measures of sleep macroarchitecture and N2/N3 microarchitecture were extracted including slow oscillation (SO), fast spindle (FS), slow spindle (SS), and spindle-SO coupling measures. DISCUSSION: In individuals with LOUE, elevated plasma p-tau217 was associated with both cognitive impairment and disrupted sleep microarchitecture, with the most pronounced cognitive deficits observed in individuals with medication refractory epilepsy. These findings support the utility of plasma p-tau217 as a biomarker in this population and underscore the role of sleep processes in the relationship between neurodegenerative pathology and cognition in older adults with epilepsy.