Exploring the relationship between everyday functioning and cognitive performance in individuals with late onset unexplained epilepsy

OBJECTIVE: Late onset unexplained epilepsy (LOUE) is linked to cognitive and functional decline, yet determinants of functional impairment are not well defined. We evaluated the Functional Activities Questionnaire (FAQ) in LOUE and examined its association with cognitive and epilepsy-related factors. METHODS: This cross-sectional study included adults with unexplained seizure onset after age 55 years, nonlesional magnetic resonance imaging, seizure onset within 5 years, and stable antiseizure medication (ASM) use. Study partners completed the FAQ; scores ≥ 6 indicated functional impairment. A delayed verbal recall composite was calculated and standardized using Harvard Aging Brain Study norms. Firth penalized logistic regression identified predictors of functional impairment. RESULTS: Among 82 participants, 12.2% were functionally impaired. Demographic characteristics were similar between groups. Impaired participants showed significantly worse cognitive performance, greater ASM use, higher rates of drug-resistant epilepsy, longer epilepsy duration, and more frequent focal impaired consciousness and generalized tonic-clonic seizures, with memory-related tasks most affected. A higher ASM number (odds ratio [OR] = 2.74, 95% confidence interval [CI] = 1.31-6.74) and a lower delayed verbal recall z-score (OR = .37, 95% CI = .14-.69) were associated with increased odds of functional impairment. SIGNIFICANCE: Functional impairment in LOUE is associated with poorer cognition and greater ASM burden. The FAQ may serve as a practical screening tool to assess functional impairment. Our study emphasizes the importance of minimizing medication burden in this population.