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.

患有癫痫症的人——尤其是病因不明的迟发性癫痫症——患痴呆症的风险更高，并且在阿尔茨海默病 (AD) 的早期阶段检测到癫痫发作，支持癫痫性 AD 前驱症状的概念。然而，癫痫和认知能力下降之间的关系仍然存在争议，关于癫痫是否会导致认知能力下降或相反，以及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，我们回顾了淀粉样蛋白-β (Aβ) 构成癫痫和认知能力下降之间共享通路的一部分的证据，特别是在 AD 的情况下。癫痫患者大脑中 Aβ 病理学负担增加，Aβ 介导的致癫痫改变已在实验研究中得到证实，有证据表明，早在斑块沉积之前，Aβ 病理学可能已经在可溶性阶段促癫痫发生。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。一系列认知测试和 Aβ 水平评估可能有助于对迟发性癫痫患者发生痴呆症的风险进行分层。如果癫痫发作是痴呆症的临床预兆，那么患有迟发性癫痫症的人可能是一个理想的群体，可以在其中实施预防或治疗策略以减缓认知能力下降。一系列认知测试和 Aβ 水平评估可能有助于对迟发性癫痫患者发生痴呆症的风险进行分层。如果癫痫发作是痴呆症的临床预兆，那么患有迟发性癫痫症的人可能是一个理想的群体，可以在其中实施预防或治疗策略以减缓认知能力下降。一系列认知测试和 Aβ 水平评估可能有助于对迟发性癫痫患者发生痴呆症的风险进行分层。如果癫痫发作是痴呆症的临床预兆，那么患有迟发性癫痫症的人可能是一个理想的群体，可以在其中实施预防或治疗策略以减缓认知能力下降。