Sleep disturbances and Alzheimers Disease
More than 70% of people with dementia are affected by Alzheimers disease (AD). Despite this high number, our understanding of the underlying mechanisms for disease progression remains very limited. However, recent studies have highlighted a link between sleep disturbances and Alzheimers disease.Sleep changes with normal aging. Over time, a decrease in time sleeping and a decrease in the quantity of NREM sleep can be observed, specifically in NREM SWS (less than 10% of the SWS is maintained). Older people also are more prone to insomnia or sleep apnea.In Alzheimers disease, in addition to cognitive decline and memory impairment, there are also significant sleep disturbances with modified sleep architecture. The latter may consist in sleep fragmentation, reduced sleep duration, insomnia, increased daytime napping, decreased quantity of some sleep stages, and a growing resemblance between some sleep stages (N1 and N2). More than 65% of people with Alzheimers disease have this type of sleep disturbance.One factor that could explain this change in sleep architecture is a change in circadian rhythm, which regulates sleep. A disruption of the circadian rhythm would generate sleep disturbances. Some studies show that people with AD have a delayed circadian rhythm, whereas in normal aging, an advanced circadian rhythm is present.In addition to these psychological symptoms, at a neurological level there are two main symptoms of Alzheimers disease. The first is an accumulation of beta-amyloid waste forming aggregate "plaques".
The second is an accumulation of tau protein.It has been shown that the sleep-wake cycle acts on the beta-amyloid burden, which is a central component found in AD. As individuals awaken, the production of beta-amyloid protein will be more consistent than its production during sleep. This is explained by two phenomena. The first is that the metabolic activity will be higher during waking, thus resulting in greater secretion of beta-amyloid protein. The second is that oxidative stress will also increase, which leads to greater AB production.On the other hand, it is during sleep that beta-amyloid residues are degraded to prevent plaque formation. The glymphatic system is responsible for this through the phenomenon of glymphatic clearance. Thus, during wakefulness, the AB burden is greater because the metabolic activity and oxidative stress are higher, and there is no protein degradation by the glymphatic clearance. During sleep, the burden is reduced as there is less metabolic activity and oxidative stress (in addition to the glymphatic clearance that occurs).Glymphatic clearance occurs during the NREM SWS sleep. This sleep stage decreases in normal aging, resulting in less glymphatic clearance and increased AB burden that will form AB plaques. Therefore, sleep disturbances in individuals with AD will amplify this phenomenon. The decrease in the quantity and quality of the NREM SWS, as well as the disturbances of sleep will therefore increase the AB plaques. This initially occurs in the hippocampus, which is a brain structure integral in long-term memory formation.