成人癫痫合并认知功能障碍危险因素进展
Progression of Risk Factors for Adult Epilepsy with Cognitive Dysfunction
DOI: 10.12677/acm.2025.1592450, PDF,    科研立项经费支持
作者: 张又文：延安大学医学院，陕西 延安；高学军*：延安大学附属医院神经内科，陕西 延安
关键词: 癫痫；认知功能障碍；危险因素；机制；Epilepsy； Cognitive Dysfunction； Risk Factors； Mechanisms
摘要: 癫痫患者中60%~70%存在认知障碍，严重影响生活质量。本文系统综述了癫痫患者认知功能障碍相关危险因素。发现癫痫相关因素包括：局灶性癫痫(尤其额、颞叶)认知损害更显著，表现为语言、执行功能缺损；全身性癫痫通常与丘脑–皮质网络异常相关。高频发作及长病程显著加剧认知衰退，可能与异常放电累积损伤相关。抗癫痫药物(AEDs)：传统AEDs (如丙戊酸、卡马西平)及多药联用对认知损害较大；新型AEDs (如左乙拉西坦、吡仑帕奈)影响较小或中性，但托吡酯可能损害执行功能。年龄增长和低教育水平是独立危险因素，后者与脑白质损伤代偿能力下降相关。抑郁、焦虑状态与认知评分显著负相关；睡眠障碍(如纺锤体活动降低)直接损害注意力与记忆。最新研究表明缺乏锻炼加重认知损伤，规律运动可改善执行功能；肠道菌群失调及血管风险(肥胖、高血压、吸烟)通过神经炎症或血流障碍加剧认知衰退。认知障碍是多重因素交互作用的结果，未来需建立预测模型实现早期干预，并积极推广健康生活方式。
Abstract: 60%~70% of patients with epilepsy have cognitive impairment, which seriously affects their quality of life. This article systematically reviews the risk factors associated with cognitive dysfunction in patients with epilepsy. Epilepsy-related factors were found to include: focal epilepsy (especially frontal and temporal lobes) has more significant cognitive impairment, manifested as language and executive function deficits; Generalized epilepsy is often associated with abnormalities in the thalamic-cortical network. Frequent episodes and long course of the disease significantly exacerbate cognitive decline and may be associated with cumulative damage from abnormal discharges. Antiepileptic drugs (AEDs): Traditional AEDs (such as valproic acid, carbamazepine) and polypharmacy have significant cognitive impairment; Newer AEDs (e.g., levetiracetam, perampanel) have a low or neutral impact, but topiramate may impair executive function. Increasing age and low education levels are independent risk factors, the latter associated with reduced compensatory capacity for white matter damage. Depression/anxiety state was significantly negatively correlated with cognitive scores. Sleep disturbances (e.g., decreased spindle activity) directly impair concentration and memory. The latest research shows that lack of exercise aggravates cognitive impairment, and regular exercise can improve executive function; Dysbiosis of the gut microbiota (e.g., Collinsella abnormalities) and vascular risk (obesity, hypertension, smoking) exacerbate cognitive decline through neuroinflammation or impaired blood flow. Cognitive impairment is the result of the interaction of multiple factors, and in the future, predictive models need to be established to achieve early intervention, control comorbidities, and actively promote healthy lifestyles.
文章引用：张又文, 高学军. 成人癫痫合并认知功能障碍危险因素进展[J]. 临床医学进展, 2025, 15(9): 10-16. https://doi.org/10.12677/acm.2025.1592450

参考文献

[1] Kanner, A.M. and Bicchi, M.M. (2022) Antiseizure Medications for Adults with Epilepsy: A Review. JAMA, 327, 1269-1281. [Google Scholar] [CrossRef] [PubMed]
[2] Ding, D., Zhou, D., Sander, J.W., Wang, W., Li, S. and Hong, Z. (2021) Epilepsy in China: Major Progress in the Past Two Decades. The Lancet Neurology, 20, 316-326. [Google Scholar] [CrossRef] [PubMed]
[3] Hermann, B.P., Dabbs, K., Becker, T., Jones, J.E., Myers y Gutierrez, A., Wendt, G., et al. (2010) Brain Development in Children with New Onset Epilepsy: A Prospective Controlled Cohort Investigation. Epilepsia, 51, 2038-2046. [Google Scholar] [CrossRef] [PubMed]
[4] 王小姗, 李亦涵, 李明昊, 等. 浅谈抗癫痫发作药物对认知功能的影响[J]. 中华神经科杂志, 2023, 56(11): 1213-1216.
[5] Fisher, R.S., Cross, J.H., French, J.A., Higurashi, N., Hirsch, E., Jansen, F.E., et al. (2017) Operational Classification of Seizure Types by the International League against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia, 58, 522-530. [Google Scholar] [CrossRef] [PubMed]
[6] Tai, X.Y., Torzillo, E., Lyall, D.M., Manohar, S., Husain, M. and Sen, A. (2023) Association of Dementia Risk with Focal Epilepsy and Modifiable Cardiovascular Risk Factors. JAMA Neurology, 80, 445-454. [Google Scholar] [CrossRef] [PubMed]
[7] Arrotta, K., Reyes, A., Kaestner, E., McDonald, C.R., Hermann, B.P., Barr, W.B., et al. (2022) Cognitive Phenotypes in Frontal Lobe Epilepsy. Epilepsia, 63, 1671-1681. [Google Scholar] [CrossRef] [PubMed]
[8] Tai, X.Y., Koepp, M., Duncan, J.S., Fox, N., Thompson, P., Baxendale, S., et al. (2016) Hyperphosphorylated Tau in Patients with Refractory Epilepsy Correlates with Cognitive Decline: A Study of Temporal Lobe Resections. Brain, 139, 2441-2455. [Google Scholar] [CrossRef] [PubMed]
[9] Lindquist, B.E., Timbie, C., Voskobiynyk, Y. and Paz, J.T. (2023) Thalamocortical Circuits in Generalized Epilepsy: Pathophysiologic Mechanisms and Therapeutic Targets. Neurobiology of Disease, 181, Article ID: 106094. [Google Scholar] [CrossRef] [PubMed]
[10] Foster, E., Malpas, C.B., Ye, K., Johnstone, B., Carney, P.W., Velakoulis, D., et al. (2020) Antiepileptic Drugs Are Not Independently Associated with Cognitive Dysfunction. Neurology, 94, e1051-e1061. [Google Scholar] [CrossRef] [PubMed]
[11] Gavrilovic, A., Toncev, G., Boskovic Matic, T., Vesic, K., Ilic Zivojinovic, J. and Gavrilovic, J. (2019) Impact of Epilepsy Duration, Seizure Control and EEG Abnormalities on Cognitive Impairment in Drug-Resistant Epilepsy Patients. Acta Neurologica Belgica, 119, 403-410. [Google Scholar] [CrossRef] [PubMed]
[12] Zawar, I., Kapur, J., Mattos, M.K., Aldridge, C.M., Manning, C. and Quigg, M. (2024) Association of Seizure Control with Cognition in People with Normal Cognition and Mild Cognitive Impairment. Neurology, 103, e209820. [Google Scholar] [CrossRef] [PubMed]
[13] Wang, L., Chen, S., Liu, C., Lin, W. and Huang, H. (2019) Factors for Cognitive Impairment in Adult Epileptic Patients. Brain and Behavior, 10, e01475. [Google Scholar] [CrossRef] [PubMed]
[14] Meador, K.J., Baker, G.A., Browning, N., Cohen, M.J., Bromley, R.L., Clayton-Smith, J., et al. (2013) Fetal Antiepileptic Drug Exposure and Cognitive Outcomes at Age 6 Years (NEAD Study): A Prospective Observational Study. The Lancet Neurology, 12, 244-252. [Google Scholar] [CrossRef] [PubMed]
[15] Simeone, T.A., Heruye, S.H., Kostansek, J.A., Yeh, M.Y., Matthews, S.A., Samson, K.K., et al. (2021) Carbamazepine Reduces Sharp Wave-Ripple Complexes and Exerts Synapse-Specific Inhibition of Neurotransmission in Ex Vivo Hippocampal Slices. Brain Sciences, 11, Article 787. [Google Scholar] [CrossRef] [PubMed]
[16] Donati, F., Gobbi, G., Campistol, J., Rapatz, G., Daehler, M., Sturm, Y., et al. (2006) Effects of Oxcarbazepine on Cognitive Function in Children and Adolescents with Partial Seizures. Neurology, 67, 679-682. [Google Scholar] [CrossRef] [PubMed]
[17] Lin, C., Chang, M. and Jhou, H. (2023) Effect of Levetiracetam on Cognition: A Systematic Review and Meta-Analysis of Double-Blind Randomized Placebo-Controlled Trials. CNS Drugs, 38, 1-14. [Google Scholar] [CrossRef] [PubMed]
[18] Perkins, J.D., Abdelmoneim, M.S., Wilkins, S.S., Kamran, S., Mesraoua, B., Melikyan, G., et al. (2023) Dosage, Time, and Polytherapy Dependent Effects of Different Levetiracetam Regimens on Cognitive Function. Epilepsy & Behavior, 148, Article ID: 109453. [Google Scholar] [CrossRef] [PubMed]
[19] Witt, J., Widman, G., Hansen, N., von Wrede, R., Elger, C.E. and Helmstaedter, C. (2022) Evaluation of a Rapid Topiramate Titration Scheme for the Early Detection of Cognitive Side Effects. CNS Drugs, 36, 1325-1330. [Google Scholar] [CrossRef] [PubMed]
[20] Witt, J. and Helmstaedter, C. (2022) The Impact of Perampanel on Cognition: A Systematic Review of Studies Employing Standardized Tests in Patients with Epilepsy. Seizure, 94, 107-111. [Google Scholar] [CrossRef] [PubMed]
[21] Witt, J., Elger, C.E. and Helmstaedter, C. (2015) Adverse Cognitive Effects of Antiepileptic Pharmacotherapy: Each Additional Drug Matters. European Neuropsychopharmacology, 25, 1954-1959. [Google Scholar] [CrossRef] [PubMed]
[22] Huang, H., Cui, G., Tang, H., Kong, L., Wang, X., Cui, C., et al. (2021) Relationships between Plasma Expression Levels of MicroRNA-146a and Microrna-132 in Epileptic Patients and Their Cognitive, Mental and Psychological Disorders. Bioengineered, 13, 941-949. [Google Scholar] [CrossRef] [PubMed]
[23] Martin, R.C., Griffith, H.R., Faught, E., Gilliam, F., Mackey, M. and Vogtle, L. (2005) Cognitive Functioning in Community Dwelling Older Adults with Chronic Partial Epilepsy. Epilepsia, 46, 298-303. [Google Scholar] [CrossRef] [PubMed]
[24] Brodie, M.J. and Kwan, P. (2005) Epilepsy in Elderly People. BMJ, 331, 1317-1322. [Google Scholar] [CrossRef] [PubMed]
[25] Miller, L.A., Galioto, R., Tremont, G., Davis, J., Bryant, K., Roth, J., et al. (2016) Cognitive Impairment in Older Adults with Epilepsy: Characterization and Risk Factor Analysis. Epilepsy & Behavior, 56, 113-117. [Google Scholar] [CrossRef] [PubMed]
[26] Wan, H., Liu, Q., Chen, C., Dong, W., Wang, S., Shi, W., et al. (2023) An Integrative Nomogram for Identifying Cognitive Impairment Using Seizure Type and Cerebral Small Vessel Disease Neuroimaging Markers in Patients with Late-Onset Epilepsy of Unknown Origin. Neurology and Therapy, 13, 107-125. [Google Scholar] [CrossRef] [PubMed]
[27] Bingaman, N., Ferguson, L., Thompson, N., Reyes, A., McDonald, C.R., Hermann, B.P., et al. (2023) The Relationship between Mood and Anxiety and Cognitive Phenotypes in Adults with Pharmacoresistant Temporal Lobe Epilepsy. Epilepsia, 64, 3331-3341. [Google Scholar] [CrossRef] [PubMed]
[28] Roliz, A.H. and Kothare, S. (2023) The Relationship between Sleep, Epilepsy, and Development: A Review. Current Neurology and Neuroscience Reports, 23, 469-477. [Google Scholar] [CrossRef] [PubMed]
[29] Huang, Y., Liu, Y., Liu, Y., Han, J., Han, H., Li, J., et al. (2023) Differences in the Topographical Distribution of Sleep Spindles among Adult Epilepsy with Cognitive Impairment. Epilepsia Open, 8, 980-990. [Google Scholar] [CrossRef] [PubMed]
[30] Tedrus, G.M.D.A.S. and Leandro-Merhi, V.A. (2023) Physical Activity in Adults with Epilepsy: Clinical Aspects and Relationship with Cognition and Quality of Life. Dementia & Neuropsychologia, 17, e20220107. [Google Scholar] [CrossRef] [PubMed]
[31] Capovilla, G., Kaufman, K.R., Perucca, E., Moshé, S.L. and Arida, R.M. (2015) Epilepsy, Seizures, Physical Exercise, and Sports: A Report from the ILAE Task Force on Sports and Epilepsy. Epilepsia, 57, 6-12. [Google Scholar] [CrossRef] [PubMed]
[32] Feter, N., Alt, R., Häfele, C.A., da Silva, M.C. and Rombaldi, A.J. (2020) Effect of Combined Physical Training on Cognitive Function in People with Epilepsy: Results from a Randomized Controlled Trial. Epilepsia, 61, 1649-1658. [Google Scholar] [CrossRef] [PubMed]
[33] Shishmanova-Doseva, M., Georgieva, K., Uzunova, Y., Ioanidu, L., Atanasova, M., Nenchovska, Z., et al. (2022) Pre-and Post-Endurance Training Mitigates the Rat Pilocarpine-Induced Status Epilepticus and Epileptogenesis-Associated Deleterious Consequences. International Journal of Molecular Sciences, 23, Article 13188. [Google Scholar] [CrossRef] [PubMed]
[34] Johnson, K.V. and Foster, K.R. (2018) Why Does the Microbiome Affect Behaviour? Nature Reviews Microbiology, 16, 647-655. [Google Scholar] [CrossRef] [PubMed]
[35] De Vadder, F., Grasset, E., Mannerås Holm, L., Karsenty, G., Macpherson, A.J., Olofsson, L.E., et al. (2018) Gut Microbiota Regulates Maturation of the Adult Enteric Nervous System via Enteric Serotonin Networks. Proceedings of the National Academy of Sciences, 115, 6458-6463. [Google Scholar] [CrossRef] [PubMed]
[36] Wiefels, M.D., Furar, E., Eshraghi, R.S., Mittal, J., Memis, I., Moosa, M., et al. (2024) Targeting Gut Dysbiosis and Microbiome Metabolites for the Development of Therapeutic Modalities for Neurological Disorders. Current Neuropharmacology, 22, 123-139. [Google Scholar] [CrossRef] [PubMed]
[37] Hong, B. (2024) Gut Flora Reflects Potential Risk Factors for Cognitive Dysfunction in Patients with Epilepsy. Journal of Health, Population and Nutrition, 43, Article No. 155. [Google Scholar] [CrossRef] [PubMed]
[38] Shakoor, M.U., Tareen, F.K., Rehman, Z., Saghir, K.A., Ashraf, W., Anjum, S.M.M., et al. (2024) Probiotics by Modulating Gut-Brain Axis Together with Brivaracetam Mitigate Seizure Progression, Behavioral Incongruities, and Prevented Neurodegeneration in Pentylenetetrazole‐Kindled Mice. CNS Neuroscience & Therapeutics, 30, e70078. [Google Scholar] [CrossRef] [PubMed]
[39] Tedrus, G.M.A.S., Leandro-Merhi, V.A., Rebelo, R.C. and da Silva, B.N. (2023) Cognition and Obesity in Adults with Epilepsy. Nutrición Hospitalaria, 40, 1033-1040. [Google Scholar] [CrossRef] [PubMed]
[40] Choi, H., Elkind, M.S.V., Longstreth, W.T., Boehme, A.K., Hafen, R., Hoyt, E.J., et al. (2022) Epilepsy, Vascular Risk Factors, and Cognitive Decline in Older Adults: The Cardiovascular Health Study. Neurology, 99, e2346-e2358. [Google Scholar] [CrossRef] [PubMed]
[41] Han, Y., Hao, G., Wang, Z., Wang, C., Qi, X., Liang, G., et al. (2024) Association between Serum Apolipoprotein E and Cognitive Function in Chinese Patients with Temporal Lobe Epilepsy. Epilepsy & Behavior, 154, Article ID: 109750. [Google Scholar] [CrossRef] [PubMed]
[42] Sapkota, S., Kobau, R., Croft, J.B., King, B.A., Thomas, C. and Zack, M.M. (2020) Prevalence and Trends in Cigarette Smoking among Adults with Epilepsy—United States, 2010-2017. MMWR. Morbidity and Mortality Weekly Report, 69, 1792-1796. [Google Scholar] [CrossRef] [PubMed]
[43] Caciagli, L., Ratcliffe, C., Xiao, F., van Graan, L.A., Trimmel, K., Vollmar, C., et al. (2023) Cognitive Phenotype of Juvenile Absence Epilepsy: An Investigation of Patients and Unaffected Siblings. Epilepsia, 64, 2792-2805. [Google Scholar] [CrossRef] [PubMed]

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