Table 5.

Summary of proposed mechanisms underlying the relationship between sleep disturbances and Alzheimer’s disease

Proposed Mechanism	Link to Alzheimer’s disease
Circadian rhythms	Circadian rhythms regulate the timing and consolidation of sleep. In AD, circadian rhythms are delayed, weakened, and misaligned
Neurodegeneration	The neurocircuitry important for regulating sleep-wake is vulnerable to early pathological changes in AD, such as tau accumulation and neurodegeneration in the brainstem
Neurotransmitters	Neurotransmitters that are important for regulating sleep-wake, such as acetylcholine, orexin, and melatonin, are also affected by AD
Neuronal hyperexcitability	More wakefulness/less sleep results in increased activity-regulated amyloid production
Glymphatic Clearance	More wakefulness/less sleep results in less clearance of Aβ and tau