Abstract
BACKGROUND: Cognitive impairment represents a major comorbidity among older adults with epilepsy. This study aimed to explore the association between the apolipoprotein E (APOE) ε4 allele and cognitive function in older people with epilepsy. METHODS: People with epilepsy aged ≥ 50 years were enrolled at an outpatient clinic of epilepsy from November 2019 to July 2024. Blood samples were collected for APOE genotyping. Participants were categorized into two groups based on the presence of the APOE ε4 allele: APOE ε4 (+/-). Cognitive function was assessed using a battery with neuropsychological tests. Based on Mini-Mental State Examination (MMSE) scores, participants were defined as unimpaired cognition (UC) (MMSE ≥ 27) and cognitive impairment (CI) (MMSE < 27). Seizure frequency was categorized into low (≤ 3/year) and high (> 3/year) groups. Multivariate logistic regression analysis and general linear models were employed to identify factors associated with cognitive function. RESULTS: Among 110 participants, 51 (46.4%) were defined as CI. Compared with UC group, the CI group was older (65.1 ± 7.6 vs 60.8 ± 6.8 years, P = 0.002), with lower educational level (9.0 [7.0, 11.0] vs 12.0 [9.0, 13.0] years, P < 0.001), and higher seizure frequency (12.0 [1.0, 24.0] vs 1.0 [0.0, 12.0] times/year, P = 0.005). High seizure frequency (OR = 3.94, 95% CI [1.34, 11.61], P = 0.013) and more APOE ε4 alleles (OR = 3.28, 95% CI [1.09, 9.83], P = 0.034) were risk factors for CI. An interactive effect between the number of APOE ε4 alleles and seizure frequency was observed (P = 0.002). Compared to participants with APOE ε4 (-) and low seizure frequency, those with APOE ε4 (-) and high seizure frequency showed a threefold risk of CI (OR = 3.34, 95% CI [0.99, 11.25], P = 0.051), while those with APOE ε4 (+) and high frequency demonstrated the highest risk of CI (OR = 10.53, 95% CI [1.75, 63.47], P = 0.010). CONCLUSIONS: The synergistic effect of APOE ε4 allele and seizure frequency on cognitive function suggested their importance in clinical assessments and therapeutic approaches in managing older people with epilepsy.