Abstract
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.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative disorder primarily characterized by deteriorating cognitive functions and neuropsychiatric symptoms [1,2,3]
This article uncovers a complex network of interactions, scoping between circadian rhythm disturbances and AD pathogenesis
The narrative form of this review should ideally demonstrate these complexities in an insightful manner as a resource that evaluates the most up-to-date knowledge related to the topics
Summary
Alzheimer’s disease (AD) is a neurodegenerative disorder primarily characterized by deteriorating cognitive functions and neuropsychiatric symptoms [1,2,3] It is the most prevalent form of dementia, accounting for at least two thirds of cases, whereas vascular dementia is second with a. Recent focus on saliency of circadian rhythm has brought an additional component when studying AD pathophysiology, and when developing or addressing therapeutic targets [19]. This narrative review represents a comprehensive approach to the relationship between circadian rhythm and AD, describing etiopathogenesis and clinical applications. A number of processes considered to be important for disease pathogenesis are pathophysiologically intertwined with the circadian system, representing potentially shared pathogenic mechanisms relevant for AD. The main reason for this is the lack of methodologically adequate clinical research and the use of transgenic animals for modelling sporadic form of the disease, which may not be an appropriate model [23]
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