Homolak Jan, Mudrovčić Monika, Vukić Barbara, Toljan Karlo
Department of Pharmacology, University of Zagreb School of Medicine, Šalata 3, Zagreb 10 000, Croatia.
University Hospital for Infectious Diseases, Mirogojska cesta 8, Zagreb 10 000, Croatia.
Med Sci (Basel). 2018 Jun 21;6(3):52. doi: 10.3390/medsci6030052.
Alzheimer's disease (AD) is a neurodegenerative disorder with a growing epidemiological importance characterized by significant disease burden. Sleep-related pathological symptomatology often accompanies AD. The etiology and pathogenesis of disrupted circadian rhythm and AD share common factors, which also opens the perspective of viewing them as a mutually dependent process. This article focuses on the bi-directional relationship between these processes, discussing the pathophysiological links and clinical aspects. Common mechanisms linking both processes include neuroinflammation, neurodegeneration, and circadian rhythm desynchronization. Timely recognition of sleep-specific symptoms as components of AD could lead to an earlier and correct diagnosis with an opportunity of offering treatments at an earlier stage. Likewise, proper sleep hygiene and related treatments ought to be one of the priorities in the management of the patient population affected by AD. This narrative review brings a comprehensive approach to clearly demonstrate the underlying complexities linking AD and circadian rhythm disruption. Most clinical data are based on interventions including melatonin, but larger-scale research is still scarce. Following a pathophysiological reasoning backed by evidence gained from AD models, novel anti-inflammatory treatments and those targeting metabolic alterations in AD might prove useful for normalizing a disrupted circadian rhythm. By restoring it, benefits would be conferred for immunological, metabolic, and behavioral function in an affected individual. On the other hand, a balanced circadian rhythm should provide greater resilience to AD pathogenesis.
阿尔茨海默病(AD)是一种神经退行性疾病,其流行病学重要性日益增加,具有显著的疾病负担。与睡眠相关的病理症状常伴随AD出现。昼夜节律紊乱与AD的病因和发病机制有共同因素,这也为将它们视为相互依存的过程提供了视角。本文重点关注这些过程之间的双向关系,讨论病理生理联系和临床方面。连接这两个过程的共同机制包括神经炎症、神经退行性变和昼夜节律失调。及时将特定睡眠症状识别为AD的组成部分,可能会实现更早且正确的诊断,并有机会在更早阶段提供治疗。同样,适当的睡眠卫生和相关治疗应该是AD患者管理的优先事项之一。这篇叙述性综述采用了一种全面的方法,以清晰展示连接AD和昼夜节律紊乱的潜在复杂性。大多数临床数据基于包括褪黑素在内的干预措施,但大规模研究仍然匮乏。遵循基于AD模型获得的证据的病理生理推理,新型抗炎治疗以及针对AD代谢改变的治疗可能被证明有助于使紊乱的昼夜节律正常化。通过恢复昼夜节律,将为受影响个体的免疫、代谢和行为功能带来益处。另一方面,平衡的昼夜节律应该能为AD发病机制提供更大的抵御能力。