Chen Yiling, Xiao Zhenxu, Zhou Xiaowen, Ding Saineng, Jiang Luxin, Zhao Qianhua, Ding Ding, Wang Jianhong, Zhu Guoxing
Department of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, China.
National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, China.
Acta Epileptol. 2025 May 23;7(1):30. doi: 10.1186/s42494-025-00213-7.
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.
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.
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).
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.
认知障碍是老年癫痫患者的一种主要合并症。本研究旨在探讨载脂蛋白E（APOE）ε4等位基因与老年癫痫患者认知功能之间的关联。
2019年11月至2024年7月期间，在一家癫痫门诊招募年龄≥50岁的癫痫患者。采集血样进行APOE基因分型。根据APOE ε4等位基因的存在情况将参与者分为两组：APOE ε4（+/-）。使用一套神经心理学测试对认知功能进行评估。根据简易精神状态检查表（MMSE）评分，将参与者定义为认知未受损（UC）（MMSE≥27）和认知障碍（CI）（MMSE<27）。癫痫发作频率分为低（≤3次/年）和高（>3次/年）两组。采用多因素逻辑回归分析和一般线性模型来确定与认知功能相关的因素。
在110名参与者中，51名（46.4%）被定义为CI。与UC组相比，CI组年龄更大（65.1±7.6岁 vs 60.8±6.8岁，P=0.002），教育水平更低（9.0[7.0，11.0]年 vs 12.0[9.0，13.0]年，P<0.001），癫痫发作频率更高（12.0[1.0，24.0]次/年 vs 1.0[0.0，12.0]次/年，P=0.005）。高癫痫发作频率（比值比[OR]=3.94，95%置信区间[CI][1.34，11.61]，P=0.013）和更多的APOE ε4等位基因（OR=3.28，95%CI[1.09，9.83]，P=0.034）是CI的危险因素。观察到APOE ε4等位基因数量与癫痫发作频率之间存在交互作用（P=0.002）。与APOE ε4（-）且癫痫发作频率低的参与者相比，APOE ε4（-）且癫痫发作频率高的参与者发生CI的风险增加了两倍（OR=3.34，95%CI[0.99，11.25]，P=0.051），而APOE ε4（+）且癫痫发作频率高的参与者发生CI的风险最高（OR=10.53，95%CI[1.75，63.47]，P=0.010）。
APOE ε4等位基因和癫痫发作频率对认知功能的协同作用表明它们在老年癫痫患者的临床评估和治疗方法中具有重要意义。
