Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira 187-8502, Japan.
Department of Neurotherapeutics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Int J Mol Sci. 2019 Feb 13;20(4):803. doi: 10.3390/ijms20040803.
Sleep disturbance is a common symptom in patients with various neurodegenerative diseases, including Alzheimer's disease (AD), and it can manifest in the early stages of the disease. Impaired sleep in patients with AD has been attributed to AD pathology that affects brain regions regulating the sleep⁻wake or circadian rhythm. However, recent epidemiological and experimental studies have demonstrated an association between impaired sleep and an increased risk of AD. These studies have led to the idea of a bidirectional relationship between AD and impaired sleep; in addition to the conventional concept that impaired sleep is a consequence of AD pathology, various evidence strongly suggests that impaired sleep is a risk factor for the initiation and progression of AD. Despite this recent progress, much remains to be elucidated in order to establish the benefit of therapeutic interventions against impaired sleep to prevent or alleviate the disease course of AD. In this review, we provide an overview of previous studies that have linked AD and sleep. We then highlight the studies that have tested the causal relationship between impaired sleep and AD and will discuss the molecular and cellular mechanisms underlying this link. We also propose future works that will aid the development of a novel disease-modifying therapy and prevention of AD via targeting impaired sleep through non-pharmacological and pharmacological interventions.
睡眠障碍是包括阿尔茨海默病（AD）在内的各种神经退行性疾病患者的常见症状，并且可能在疾病的早期阶段出现。AD 患者的睡眠障碍归因于影响调节睡眠-觉醒或昼夜节律的大脑区域的 AD 病理学。然而，最近的流行病学和实验研究表明，睡眠障碍与 AD 的风险增加之间存在关联。这些研究提出了 AD 和睡眠障碍之间存在双向关系的观点；除了睡眠障碍是 AD 病理学后果的传统概念外，各种证据强烈表明睡眠障碍是 AD 发病和进展的危险因素。尽管取得了这一最新进展，但仍有许多问题需要阐明，以便确定针对睡眠障碍的治疗干预措施预防或减轻 AD 病程的益处。在这篇综述中，我们提供了之前将 AD 和睡眠联系起来的研究概述。然后，我们强调了测试睡眠障碍与 AD 之间因果关系的研究，并将讨论这种联系的分子和细胞机制。我们还提出了未来的工作，这将通过针对睡眠障碍的非药物和药物干预来帮助开发一种新的疾病修饰疗法并预防 AD。
