Sleep Disorders Associated With Alzheimer's Disease: A Perspective

Abstract

Sleep disturbances, as well as sleep-wake rhythm disturbances, are typical symptoms of Alzheimer's disease (AD) that may precede the other clinical signs of this neurodegenerative disease. Here, we describe clinical features of sleep disorders in AD and the relation between sleep disorders and both cognitive impairment and poor prognosis of the disease. There are difficulties of the diagnosis of sleep disorders based on sleep questionnaires, polysomnography or actigraphy in the AD patients. Typical disturbances of the neurophysiological sleep architecture in the course of the AD include deep sleep and paradoxical sleep deprivation. Among sleep disorders occurring in patients with AD, the most frequent disorders are sleep breathing disorders and restless legs syndrome. Sleep disorders may influence circadian fluctuations of the concentrations of amyloid-β in the interstitial brain fluid and in the cerebrovascular fluid related to the glymphatic brain system and production of the amyloid-β. There is accumulating evidence suggesting that disordered sleep contributes to cognitive decline and the development of AD pathology. In this mini-review, we highlight and discuss the association between sleep disorders and AD.

Keywords: AD; diagnosis; disturbance; sleep disorders; sleep-rhythm.

Figure 1

Identification of sleep disorders and possible relationship with AD. Several sleep conditions may indicate the risk of undergo AD; for example, nighttime sleep (<5 h) is linked in many epidemiological studies as a risk factor for AD. Additionally, it is possible to qualitatively survey for sleep quality by means of questionnaires i.e., Athens Insomnia Scale or Pittsburg Sleep Quality Index. Polysomnography is a procedure to diagnose sleep disorders, and in AD patients, it is observed prolonged sleep latency and increased number of arousals. Finally, some portable equipment like Actigraph can provide key data of sleep quality by measuring the wakefulness and sleep activity in several days (10 days registration).

Figure 2

Breathing disorders and amyloid beta clearance. It has been observed that sleep disorders in AD can be caused by obstructive sleep apnea (OSA). OSA is caused by an obstruction of respiratory airways, and its main risk overweight in obesity. Prospective studies have shown that patients with OSA may develop AD by several mechanisms such as neuroinflammation, oxidative stress and hypoxemia. Interestingly, clinical conditions like periodic limb movements and restless legs syndrome, which also lead to sleep disturbances, may be associated to AD. The removal of metabolites and neurotoxic compounds via glymphatic system is a function regulated by sleep and wakefulness activity. It is known that soluble amyloid beta can be cleared from the CNS parenchyma using the glymphatic system. Sleep may influence the clearance of amyloid beta due to the increased brain's interstitial space possibly by the shrinkage of astroglial cells.