ArticleNeurology2026
Association Between Alzheimer Pathology, Sleep, and Cognition in Patients With Late-Onset Unexplained Epilepsy.
Article in Neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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12 authors.
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Abstract
BACKGROUND AND
objectivesLate-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.
methodsParticipants 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.
resultsEighty-five participants enrolled (mean age 71.3 ± 7.1 years; 49% female). The average PACC5 Z score (±SD) was -0.63 ± 1.0. Higher plasma levels of log-transformed p-tau217 (per 1 unit increase) were associated with poorer cognition, PACC5 (β = -0.66; 95% CI -1.19 to -0.13; 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.
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