Neurology Clinic, Department of Medicine and Surgery, University of Perugia - S. Maria della Misericordia Hospital, Perugia, Italy.
Oxford Epilepsy Research Group, NIHR Biomedical Research Centre, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.
Nat Rev Neurol. 2021 Aug;17(8):469-485. doi: 10.1038/s41582-021-00505-9. Epub 2021 Jun 11.
People with epilepsy - in particular, late-onset epilepsy of unknown aetiology - have an elevated risk of dementia, and seizures have been detected in the early stages of Alzheimer disease (AD), supporting the concept of an epileptic AD prodrome. However, the relationship between epilepsy and cognitive decline remains controversial, with substantial uncertainties about whether epilepsy drives cognitive decline or vice versa, and whether shared pathways underlie both conditions. Here, we review evidence that amyloid-β (Aβ) forms part of a shared pathway between epilepsy and cognitive decline, particularly in the context of AD. People with epilepsy show an increased burden of Aβ pathology in the brain, and Aβ-mediated epileptogenic alterations have been demonstrated in experimental studies, with evidence suggesting that Aβ pathology might already be pro-epileptogenic at the soluble stage, long before plaque deposition. We discuss the hypothesis that Aβ mediates - or is at least a major determinant of - a continuum spanning epilepsy and cognitive decline. Serial cognitive testing and assessment of Aβ levels might be worthwhile to stratify the risk of developing dementia in people with late-onset epilepsy. If seizures are a clinical harbinger of dementia, people with late-onset epilepsy could be an ideal group in which to implement preventive or therapeutic strategies to slow cognitive decline.
患有癫痫的人 - 特别是病因不明的迟发性癫痫 - 痴呆的风险增加，并且在阿尔茨海默病（AD）的早期阶段已经发现了癫痫发作，支持癫痫 AD 前驱期的概念。然而，癫痫与认知能力下降之间的关系仍然存在争议，对于癫痫是否导致认知能力下降，或者反之亦然，以及这两种情况是否存在共同的途径，存在很大的不确定性。在这里，我们回顾了证据，表明淀粉样蛋白-β（Aβ）是癫痫和认知能力下降之间共同途径的一部分，特别是在 AD 的情况下。患有癫痫的人在大脑中表现出 Aβ 病理学负担增加，并且在实验研究中已经证明了 Aβ 介导的致癫痫改变，有证据表明 Aβ 病理学可能已经在可溶性阶段具有致癫痫作用，远远早于斑块沉积。我们讨论了 Aβ 介导 - 或至少是跨越癫痫和认知能力下降的连续体的主要决定因素的假设。连续的认知测试和 Aβ 水平评估可能有助于对迟发性癫痫患者的痴呆风险进行分层。如果癫痫发作是痴呆的临床先兆，那么患有迟发性癫痫的人可能是实施预防或治疗策略以减缓认知能力下降的理想人群。
