medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»10.33667/2078-5631-2025-15-46-50medalphabet-4469Research ArticleСтатьиЭпилепсия при болезни Альцгеймера: патофизиологические механизмы и особенности диагностикиEpilepsy in alzheimer's disease: pathophysiological mechanisms and diagnostic featureshttps://orcid.org/0000-0003-1345-1049АжиговаА. М.AzhigovaA. M.

Ажигова Ася Магометовна, к.м.н., врач-невролог неврологического отделения Университетской клиники

Москва

Azhigova Asya M., PhD Med, neurologist at Dept of Neurology

https://orcid.org/0009-0004-5876-350XКоноваловаТ. И.KonovalovaT. I.

Коновалова Татьяна Ивановна, врач-невролог

Волгоград

Konovalova Tatyana I., neurologist

https://orcid.org/0000-0001-8321-5864ВласовП. Н.VlasovP. N.

Власов Павел Николаевич, д.м.н., проф. кафедры неврологии

Москва

Vlasov Pavel N., DM Sci (habil.), professor, head of Dept of Neurology

ФГБОУ ВО «Российский университет медицины» Минздрава РоссииРоссияRussian University of MedicineRussian FederationЦентр неврологии, диагностики и лечения эпилепсии ООО «ЭпиЦентр»РоссияCenter for Neurology, Diagnosis and Treatment of Epilepsy LLC «EpiCenter»Russian Federation202526072025015«Неврология и психиатрия» (2)4650Copyright © Ажигова А.М., Коновалова Т.И., Власов П.Н., 20252025Ажигова А.М., Коновалова Т.И., Власов П.Н.Azhigova A.M., Konovalova T.I., Vlasov P.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-alphabet.com/jour/article/view/4469

Эпилептические приступы при болезни Альцгеймера (БА) представляют собой значимую клиническую проблему, существенно влияющую на течение заболевания и качество жизни пациентов. В данном обзоре рассматриваются современные представления о патофизиологических механизмах развития пароксизмальной активности при БА, включая роль β-амилоида, тау-протеина и нейровоспаления. Особое внимание уделяется новым диагностическим подходам, включая биомаркеры, методы нейровизуализации и протоколы ЭЭГ-мониторинга. Анализируются клинические особенности эпилептических приступов при БА, их классификация и возрастные различия в манифестации. Обсуждается проблема гиподиагностики эпилепсии при БА, достигающей 70 % случаев в рутинной клинической практике. Представлены современные алгоритмы диагностики и клинические рекомендации. Обзор подчеркивает необходимость междисциплинарного подхода к диагностике и важность ранней идентификации эпилептической активности как потенциального маркера нейродегенеративного процесса.

Epileptic seizures in Alzheimer's disease (AD) represent a significant clinical challenge that substantially affects disease progression and patients' quality of life. This review examines current understanding of the pathophysiological mechanisms underlying paroxysmal activity in AD, including the role of β-amyloid, tau protein, and neuroinflammation. Special attention is given to novel diagnostic approaches, including biomarkers, neuroimaging techniques, and EEG monitoring protocols. The clinical features of epileptic seizures in AD, their classification, and age-related differences in manifestation are analyzed. The review addresses the problem of epilepsy underdiagnosis in AD, which reaches 70% of cases in routine clinical practice. Current diagnostic algorithms and clinical guidelines are presented. The review emphasizes the necessity of an interdisciplinary approach to diagnosis and the importance of early identification of epileptic activity as a potential marker of neurodegenerative process.

болезнь АльцгеймераэпилепсиянейродегенерациябиомаркерыЭЭГ-мониторингнейровоспалениеβ-амилоидсубклинические приступыранняя диагностикаAlzheimer's diseaseepilepsyneurodegenerationbiomarkersEEG monitoringneuroinflammationβ-amyloidsubclinical seizuresearly diagnosisReferencesBorn H. A. Seizures in Alzheimer's disease. Neuroscience. 2015; 286: 251–263. DOI: 10.1016/j.neuroscience.2014.11.051Born H. A. Seizures in Alzheimer's disease. Neuroscience. 2015; 286: 251–263. DOI: 10.1016/j.neuroscience.2014.11.051Vossel K. A., Beagle A. J., Rabinovici G. D. et al. Seizures and Epileptiform Activity in the Early Stages of Alzheimer Disease. JAMA Neurology. 2013; 70 (9): 1158–1166. DOI: 10.1001/jamaneurol.2013.136Vossel K. A., Beagle A. J., Rabinovici G. D. et al. Seizures and Epileptiform Activity in the Early Stages of Alzheimer Disease. JAMA Neurology. 2013; 70 (9): 1158–1166. DOI: 10.1001/jamaneurol.2013.136Shin J. H. Dementia Epidemiology Fact Sheet 2022. Annals of Rehabilitation Medicine. 2022; 46 (2): 53–59. DOI: 10.5535/arm.22027Shin J. H. Dementia Epidemiology Fact Sheet 2022. Annals of Rehabilitation Medicine. 2022; 46 (2): 53–59. DOI: 10.5535/arm.22027Pandis D., Scarmeas N. Seizures in Alzheimer disease: clinical and epidemiological data. Epilepsy Currents. 2012; 12 (5): 184–187. DOI: 10.5698/1535-7511-12.5.184Pandis D., Scarmeas N. Seizures in Alzheimer disease: clinical and epidemiological data. Epilepsy Currents. 2012; 12 (5): 184–187. DOI: 10.5698/1535-7511-12.5.184Friedman D., Honig L. S., Scarmeas N. Seizures and epilepsy in Alzheimer's disease. CNS Neuroscience & Therapeutics. 2012; 18 (4): 285–294. DOI: 10.1111/j.17555949.2011.00251.xFriedman D., Honig L. S., Scarmeas N. Seizures and epilepsy in Alzheimer's disease. CNS Neuroscience & Therapeutics. 2012; 18 (4): 285–294. DOI: 10.1111/j.17555949.2011.00251.xRipoli C., Cocco S., Li Puma D. et al. Intracellular accumulation of amyloid-β (Aβ) protein plays a major role in Aβ-induced alterations of glutamatergic synaptic transmission and plasticity. Journal of Neuroscience. 2014; 34: 12893–12903. DOI: 10.1523/ jneurosci.1201-14.2014Ripoli C., Cocco S., Li Puma D. et al. Intracellular accumulation of amyloid-β (Aβ) protein plays a major role in Aβ-induced alterations of glutamatergic synaptic transmission and plasticity. Journal of Neuroscience. 2014; 34: 12893–12903. DOI: 10.1523/ jneurosci.1201-14.2014Hector A., Brouillette J. Hyperactivity Induced by Soluble Amyloid-β Oligomers in the Early Stages of Alzheimer's Disease. Frontiers in Molecular Neuroscience. 2021; 13: 600084. DOI: 10.3389/fnmol.2020.600084Hector A., Brouillette J. Hyperactivity Induced by Soluble Amyloid-β Oligomers in the Early Stages of Alzheimer's Disease. Frontiers in Molecular Neuroscience. 2021; 13: 600084. DOI: 10.3389/fnmol.2020.600084Palop J. J., Mucke L. Network abnormalities and interneuron dysfunction in Alzheimer disease. Nature Reviews Neuroscience. 2016; 17 (12): 777–792. DOI: 10.1038/nrn.2016.141Palop J. J., Mucke L. Network abnormalities and interneuron dysfunction in Alzheimer disease. Nature Reviews Neuroscience. 2016; 17 (12): 777–792. DOI: 10.1038/nrn.2016.141Sánchez M. P., García-Cabrero A.M., Sánchez-Elexpuru G. et al. Tau-Induced Pathology in Epilepsy and Dementia: Notions from Patients and Animal Models. International Journal of Molecular Sciences. 2018; 19 (4): 1092. DOI: 10.3390/ijms19041092Sánchez M. P., García-Cabrero A.M., Sánchez-Elexpuru G. et al. Tau-Induced Pathology in Epilepsy and Dementia: Notions from Patients and Animal Models. International Journal of Molecular Sciences. 2018; 19 (4): 1092. DOI: 10.3390/ijms19041092Vezzani A., Friedman A., Dingledine R. J. The role of inflammation in epileptogenesis. Neuropharmacology. 2013; 69 16–24. DOI: 10.1016/j.neuropharm.2012.04.004Vezzani A., Friedman A., Dingledine R. J. The role of inflammation in epileptogenesis. Neuropharmacology. 2013; 69 16–24. DOI: 10.1016/j.neuropharm.2012.04.004Sanz P., Rubio T., Garcia-Gimeno M. A. Neuroinflammation and Epilepsy: From Pathophysiology to Therapies Based on Repurposing Drugs. International Journal of Molecular Sciences. 2024; 25 (8): 4161. DOI: 10.3390/ijms25084161Sanz P., Rubio T., Garcia-Gimeno M. A. Neuroinflammation and Epilepsy: From Pathophysiology to Therapies Based on Repurposing Drugs. International Journal of Molecular Sciences. 2024; 25 (8): 4161. DOI: 10.3390/ijms25084161Zarea A., Charbonnier C., Rovelet-Lecrux A. et al. Seizures in dominantly inherited Alzheimer disease. Neurology. 2016; 87 (9): 912–919. DOI: 10.1212/WNL.0000000000003048Zarea A., Charbonnier C., Rovelet-Lecrux A. et al. Seizures in dominantly inherited Alzheimer disease. Neurology. 2016; 87 (9): 912–919. DOI: 10.1212/WNL.0000000000003048Najm R., Jones E. A., Huang Y. Apolipoprotein E 4, inhibitory network dysfunction, and Alzheimer's disease. Molecular Neurodegeneration. 2019; 14 (1). 24. DOI: 10.1186/ s13024-019-0324-6Najm R., Jones E. A., Huang Y. Apolipoprotein E 4, inhibitory network dysfunction, and Alzheimer's disease. Molecular Neurodegeneration. 2019; 14 (1). 24. DOI: 10.1186/ s13024-019-0324-6Hanke J. M., Schindler K. A., Seiler A. On the relationships between epilepsy, sleep, and Alzheimer's disease: A narrative review. Epilepsy & Behavior. 2022; 129: 108609. DOI: 10.1016/j.yebeh.2022.108609Hanke J. M., Schindler K. A., Seiler A. On the relationships between epilepsy, sleep, and Alzheimer's disease: A narrative review. Epilepsy & Behavior. 2022; 129: 108609. DOI: 10.1016/j.yebeh.2022.108609Cretin B., Sellal F., Philippi N. et al. Epileptic prodromal Alzheimer's disease, a retrospective study of 13 new cases: expanding the spectrum of Alzheimer's disease to an epileptic variant? Journal of Alzheimer's Disease. 2016; 52: 1125–1133. DOI: 10.3233/JAD-150096Cretin B., Sellal F., Philippi N. et al. Epileptic prodromal Alzheimer's disease, a retrospective study of 13 new cases: expanding the spectrum of Alzheimer's disease to an epileptic variant? Journal of Alzheimer's Disease. 2016; 52: 1125–1133. DOI: 10.3233/JAD-150096Rao S. C., Dove G., Cascino G. D., Petersen R. C. Recurrent seizures in patients with dementia: frequency, seizure types, and treatment outcome. Epilepsy & Behavior. 2009; 14: 118–120. DOI: 10.1016/j.yebeh.2008.08.012Rao S. C., Dove G., Cascino G. D., Petersen R. C. Recurrent seizures in patients with dementia: frequency, seizure types, and treatment outcome. Epilepsy & Behavior. 2009; 14: 118–120. DOI: 10.1016/j.yebeh.2008.08.012Sarkis R. A., Dickerson B. C., Cole A. J., Chemali Z. N. Clinical and neurophysiologic characteristics of unprovoked seizures in patients diagnosed with dementia. Journal of Neuropsychiatry and Clinical Neurosciences. 2016; 28: 56–61. DOI: 10.1176/appi. neuropsych.15060143Sarkis R. A., Dickerson B. C., Cole A. J., Chemali Z. N. Clinical and neurophysiologic characteristics of unprovoked seizures in patients diagnosed with dementia. Journal of Neuropsychiatry and Clinical Neurosciences. 2016; 28: 56–61. DOI: 10.1176/appi. neuropsych.15060143Vossel K. A., Ranasinghe K. G., Beagle A. J. et al. Incidence and impact of subclinical epileptiform activity in Alzheimer's disease. Annals of Neurology. 2016; 80: 858–870. DOI: 10.1002/ana.24794Vossel K. A., Ranasinghe K. G., Beagle A. J. et al. Incidence and impact of subclinical epileptiform activity in Alzheimer's disease. Annals of Neurology. 2016; 80: 858–870. DOI: 10.1002/ana.24794Horvath A. A., Papp A., Zsuffa J. et al. Subclinical epileptiform activity accelerates the progression of Alzheimer's disease: A long-term EEG study. Clinical Neurophysiology. 2021; 132 (8): 1982–1989. DOI: 10.1016/j.clinph.2021.03.050Horvath A. A., Papp A., Zsuffa J. et al. Subclinical epileptiform activity accelerates the progression of Alzheimer's disease: A long-term EEG study. Clinical Neurophysiology. 2021; 132 (8): 1982–1989. DOI: 10.1016/j.clinph.2021.03.050Hermann P., Zerr I. Rapidly progressive dementias – aetiologies, diagnosis and management. Nature Reviews Neurology. 2022; 18 (6.): 363–376. DOI: 10.1038/s41582-022-00659-0Hermann P., Zerr I. Rapidly progressive dementias – aetiologies, diagnosis and management. Nature Reviews Neurology. 2022; 18 (6.): 363–376. DOI: 10.1038/s41582-022-00659-0Mauricio E. A., Freeman W. D. Status epilepticus in the elderly: differential diagnosis and treatment. Neuropsychiatric Disease and Treatment. 2011; 7: 161–166. DOI: 10.2147/NDT.S 10537Mauricio E. A., Freeman W. D. Status epilepticus in the elderly: differential diagnosis and treatment. Neuropsychiatric Disease and Treatment. 2011; 7: 161–166. DOI: 10.2147/NDT.S 10537Lezaic N., Roussy J., Masson H. et al. Epilepsy in the elderly: Unique challenges in an increasingly prevalent population. Epilepsy & Behavior. 2020; 102: 106724. DOI: 10.1016/j. yebeh.2019.106724Lezaic N., Roussy J., Masson H. et al. Epilepsy in the elderly: Unique challenges in an increasingly prevalent population. Epilepsy & Behavior. 2020; 102: 106724. DOI: 10.1016/j. yebeh.2019.106724Tang M., Ryman D. C., McDade E. et al. Neurological manifestations of autosomal dominant familial Alzheimer's disease: a comparison of the published literature with the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS). The Lancet Neurology. 2016; 15 (13): 1317–1325. DOI: 10.1016/S 1474-4422 (16) 30229-0Tang M., Ryman D. C., McDade E. et al. Neurological manifestations of autosomal dominant familial Alzheimer's disease: a comparison of the published literature with the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS). The Lancet Neurology. 2016; 15 (13): 1317–1325. DOI: 10.1016/S 1474-4422 (16) 30229-0Tábuas-Pereira M., Durães J., Lopes J. et al. Increased CSF tau is associated with a higher risk of seizures in patients with Alzheimer's disease. Epilepsy & Behavior. 2019; 98 (Pt A): 207–209. DOI: 10.1016/j.yebeh.2019.06.033Tábuas-Pereira M., Durães J., Lopes J. et al. Increased CSF tau is associated with a higher risk of seizures in patients with Alzheimer's disease. Epilepsy & Behavior. 2019; 98 (Pt A): 207–209. DOI: 10.1016/j.yebeh.2019.06.033Liew Y., Retinasamy T., Arulsamy A., Ali I., Jones N. C., O'Brien T.J., Shaikh M. F. Neuroinflammation: A Common Pathway in Alzheimer's Disease and Epilepsy. Journal of Alzheimer's Disease. 2023; 94(s1): S 253–S 265. DOI: 10.3233/JAD-230059‌Liew Y., Retinasamy T., Arulsamy A., Ali I., Jones N. C., O'Brien T.J., Shaikh M. F. Neuroinflammation: A Common Pathway in Alzheimer's Disease and Epilepsy. Journal of Alzheimer's Disease. 2023; 94(s1): S 253–S 265. DOI: 10.3233/JAD-230059‌Alcantara-Gonzalez D., Villasana-Salazar B., Peña-Ortega F. Single amyloid-beta injection exacerbates 4-aminopyridine-induced seizures and changes synaptic coupling in the hippocampus. Hippocampus. 2019; 29: 1150–1164. DOI: 10.1002/hipo.23126Alcantara-Gonzalez D., Villasana-Salazar B., Peña-Ortega F. Single amyloid-beta injection exacerbates 4-aminopyridine-induced seizures and changes synaptic coupling in the hippocampus. Hippocampus. 2019; 29: 1150–1164. DOI: 10.1002/hipo.23126Dou W., Zhao L., Su C. et al. A quantitative MRI index for assessing the severity of hippocampal sclerosis in temporal lobe epilepsy. BMC Medical Imaging. 2020; 20: 42. DOI: 10.1186/s12880-020-00440-zDou W., Zhao L., Su C. et al. A quantitative MRI index for assessing the severity of hippocampal sclerosis in temporal lobe epilepsy. BMC Medical Imaging. 2020; 20: 42. DOI: 10.1186/s12880-020-00440-zSaidlitz P., Voisin T., Vellas B. et al. Amyloid imaging in Alzheimer's disease: a literature review. The Journal of Nutrition, Health & Aging. 2014; 18 (7): 723–740. DOI: 10.1007/ s12603-014-0507-3Saidlitz P., Voisin T., Vellas B. et al. Amyloid imaging in Alzheimer's disease: a literature review. The Journal of Nutrition, Health & Aging. 2014; 18 (7): 723–740. DOI: 10.1007/ s12603-014-0507-3Krishnadas N., Villemagne V. L., Doré V., Rowe C. C. Advances in Brain Amyloid Imaging. Seminars in Nuclear Medicine. 2021; 51 (3): 241–252. DOI: 10.1053/j.semnuclmed.2020.12.005Krishnadas N., Villemagne V. L., Doré V., Rowe C. C. Advances in Brain Amyloid Imaging. Seminars in Nuclear Medicine. 2021; 51 (3): 241–252. DOI: 10.1053/j.semnuclmed.2020.12.005Fountain N. B., Kim J. S., Lee S. I. Sleep deprivation activates epileptiform discharges independent of the activating effects of sleep. Journal of Clinical Neurophysiology. 1998. 15. 69–75. DOI: 10.1097/00004691-199801000-00009Fountain N. B., Kim J. S., Lee S. I. Sleep deprivation activates epileptiform discharges independent of the activating effects of sleep. Journal of Clinical Neurophysiology. 1998. 15. 69–75. DOI: 10.1097/00004691-199801000-00009Ramsay R. E., Rowan A. J., Pryor F. M. Special considerations in treating the elderly patient with epilepsy. Neurology. 2004; 62 (5, Suppl 2): P. S 24–S 29. DOI: 10.1212/ wnl.62.5_suppl_2.s24Ramsay R. E., Rowan A. J., Pryor F. M. Special considerations in treating the elderly patient with epilepsy. Neurology. 2004; 62 (5, Suppl 2): P. S 24–S 29. DOI: 10.1212/ wnl.62.5_suppl_2.s24Horváth A., Szűcs A., Hidasi Z. et al. Prevalence, Semiology, and Risk Factors of Epilepsy in Alzheimer's Disease: An Ambulatory EEG Study. Journal of Alzheimer's Disease. 2018; 63 (3): 1045–1054. DOI: 10.3233/JAD-170925Horváth A., Szűcs A., Hidasi Z. et al. Prevalence, Semiology, and Risk Factors of Epilepsy in Alzheimer's Disease: An Ambulatory EEG Study. Journal of Alzheimer's Disease. 2018; 63 (3): 1045–1054. DOI: 10.3233/JAD-170925Cretin B., Philippi N., Bousiges O. et al. Do we know how to diagnose epilepsy early in Alzheimer's disease? Revue Neurologique. 2017; 173 (6): 374–380. DOI: 10.1016/j. neurol.2017.03.028Cretin B., Philippi N., Bousiges O. et al. Do we know how to diagnose epilepsy early in Alzheimer's disease? Revue Neurologique. 2017; 173 (6): 374–380. DOI: 10.1016/j. neurol.2017.03.028Devulder A., Macea J., Kalkanis A. et al. Subclinical epileptiform activity and sleep disturbances in Alzheimer's disease. Brain and Behavior. 2023; 13 (12): e3306. DOI: 10.1002/brb3.3306Devulder A., Macea J., Kalkanis A. et al. Subclinical epileptiform activity and sleep disturbances in Alzheimer's disease. Brain and Behavior. 2023; 13 (12): e3306. DOI: 10.1002/brb3.3306Sen A., Jette N., Husain M., Sander J. W. Epilepsy in older people. The Lancet. 2020; 395 (10225): 735–748. DOI: 10.1016/S 0140-6736 (19) 33064-8Sen A., Jette N., Husain M., Sander J. W. Epilepsy in older people. The Lancet. 2020; 395 (10225): 735–748. DOI: 10.1016/S 0140-6736 (19) 33064-8Петров В. А., Иванов С. Н., Смирнова Е. В. Клинические рекомендации по диагностике и лечению эпилепсии. Неврология. 2023; 25 (3): 45–67.Петров В. А., Иванов С. Н., Смирнова Е. В. Клинические рекомендации по диагностике и лечению эпилепсии. Неврология. 2023; 25 (3): 45–67.Petrov V. A., Ivanov S. N., Smirnova E. V. Clinical recommendations for the diagnosis and treatment of epilepsy. Neurology. 2023; 25 (3): 45–67. (In Russ.).Petrov V. A., Ivanov S. N., Smirnova E. V. Clinical recommendations for the diagnosis and treatment of epilepsy. Neurology. 2023; 25 (3): 45–67. (In Russ.).

The authors declare that there are no conflicts of interest present.