P155: Circadian Rhythms and Alzheimer's Disease

Abstract

Introduction:

Major neurocognitive disorder (or simply Dementia) is one of the main causes of disability and burden disease to caregivers and the health system, and a frequent cause of mortality worldwide. Alzheimer`s disease (AD) is the most common type (60-70%).

AD is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) deposition, causing neuronal and synaptic loss with subsequent cognitive disfunction.

There is cumulating evidence that sleep disturbances are associated with several pathological conditions, and AD is one of these. The prevalence and severity of sleep disorders is significant in AD patients, with sleep disturbances often precede its clinical diagnosis in many years. Some studies focus on possible mechanisms by which (abnormal) sleep participate in AD pathogenesis, and concluded individuals with sleep disturbances are at higher risk of developing dementia.

Objectives:

To highlight the current evidence on whether sleep disorders could precipitate or accelerate the clinical course of AD.

Methods:

Non-systematic review about sleep abnormalities and AD pathogenesis.

Results:

Several authors described a two-way relationship between sleep and amyloid pathology - sleep deprivation would lead to increased production and decreased clearance of Aβ; once Aβ is accumulated it results in more disrupted sleep, with an increase of Aβ production during wakefulness and a decrease of its clearance during sleep.

Recent data showed that sleep continuity and architecture (decreased total sleep time, slow-wave sleep, and REM sleep) are disturbed in AD patients.

Otherwise, sleep deprivation may be associated with decreased glymphatic system clearance, leading to accumulation of neurotoxic proteins, particularly Aβ (and tau). It`s also associated with proinflammatory states due to accumulation of reactive oxygen species, nucleotides and proteins during wakefulness, which leads to immune response that causes neuronal dysfunction and cellular death. Insomnia and sleep deprivation were also associated with activation of complement pathway and immunoglobulins secretion. Many studies suggest chronic sleep disruption changes blood–brain barrier structure and function leading to Aβ accumulation.

Conclusions:

There is emerging evidence that points sleep disturbances as both a potential marker for AD pathology and risk predictor of developing the disease. Future investigations should evaluate the relationship between specific sleep disorders and AD physiopathology.