Exploring Potential Mechanisms of Sleep Disorders in Alzheimer's Dementia: A Scoping Review

Alzheimer's dementia (AD) is characterized by a progressive decline in behavioral and cognitive functions, with sleep disorders (SDs) increasingly recognized as one of the noncognitive symptoms. Sleep plays a critical role in the brain, supporting learning and memory, regulating synaptic plasticity, and facilitating waste clearance. However, the mechanisms underlying sleep disturbances in AD remain poorly understood. This review aims to explore these mechanisms and their potential relevance for clinicians managing AD. A systematic search was conducted across multiple sources and databases, using keywords such as "Alzheimer AND sleep disorder", along with terms related to neurodegeneration and sleep disturbances. Of the 1,511 records identified, 18 were included in the final analysis. The findings highlight several mechanisms linking AD and SDs, suggesting a bidirectional relationship. These mechanisms include (i) shared genetic factors; (ii) disruption of the glymphatic system; (iii) circadian system dysregulation; (iv) neuroinflammation; (v) abnormal functional connectivity between related brain regions; and (vi) atrophy in brain regions involved in memory and sleep. In conclusion, the relationship between AD and SDs is complex and bidirectional. Sleep disturbances not only precede the onset of AD but also worsen as the disease progresses. Sleep may, therefore, serve as a promising biomarker for AD, with targeting sleep disturbances offering a potential early therapeutic strategy in managing AD.