System and Applied Pharmacology@University Magna Grecia (FAS@UMG) Research Center, Science of Health Department, School of Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy.
Neurology Clinic, Department of Medicine and Surgery, University of Perugia, Santa Maria Della Misericordia Hospital, Perugia, Italy.
Curr Neuropharmacol. 2022;20(11):2029-2033. doi: 10.2174/1570159X20666220507020635.
The literature on epileptic seizures in Alzheimer's disease has significantly increased over the past decades. Remarkably, several studies suggest a bi-directional link between these two common neurological diseases, with either condition carrying a nearly 2-fold risk of contracting the other in comparison to healthy subjects. In this respect, evidence from both clinical and preclinical studies indicates that epileptogenesis and neurodegeneration possibly share common underlying mechanisms. However, the precise association between epileptogenesis and neurodegeneration still needs to be fully elucidated. Targeted intervention to reduce abnormal network hyperexcitability might constitute a therapeutic strategy to postpone the onset of later neurodegenerative changes and consequent cognitive decline by many years in patients. By virtue of this, an early diagnosis and treatment of seizures in patients with Alzheimer's disease should be pursued. To date, no guidelines are available for treating epileptic activity in this context, largely due to the paucity of studies sufficient to answer the related questions. Accordingly, clinical trials are mandatory, not only to inform clinicians about symptomatic management of seizures in Alzheimer's disease patients but also to detect if treatment with antiseizure medications could have disease-modifying effects. Moreover, it will be fundamental to expand the application of animal models of Alzheimer's disease to comorbid conditions, such as epilepsy both to reveal the mechanisms underlying seizure onset and to better define their role in cognitive decline. Such models could also be useful to identify pharmacological compounds having therapeutically effectiveness as well as reliable early biomarkers for seizures in Alzheimer's disease.
过去几十年来,阿尔茨海默病相关癫痫发作的文献显著增加。值得注意的是,有几项研究表明这两种常见的神经退行性疾病之间存在双向联系,与健康受试者相比,这两种疾病都使另一种疾病的发病风险增加近两倍。在这方面,临床和临床前研究的证据表明,癫痫发作和神经退行性变可能具有共同的潜在机制。然而,癫痫发作和神经退行性变之间的确切关联仍需要充分阐明。针对减少异常网络过度兴奋的靶向干预可能构成一种治疗策略,可以在许多年内推迟患者出现晚期神经退行性变化和随后的认知能力下降。因此,应该对阿尔茨海默病患者的癫痫发作进行早期诊断和治疗。迄今为止,由于缺乏足够的研究来回答相关问题,针对这种情况,尚无治疗癫痫活动的指南。因此,进行临床试验是必要的,不仅要为临床医生提供关于阿尔茨海默病患者癫痫发作的症状性管理的信息,还要检测抗癫痫药物治疗是否具有疾病修饰作用。此外,将阿尔茨海默病动物模型的应用扩展到合并症(如癫痫)也很重要,以便揭示癫痫发作的潜在机制,并更好地定义其在认知能力下降中的作用。此类模型还可以用于识别具有治疗效果的药物化合物以及阿尔茨海默病癫痫发作的可靠早期生物标志物。