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Alzheimer's and sleep

Alzheimer's disease is a neurodegenerative disease that was first documented in 1906 by Alois AlzheimerSORIA LOPEZ; GONZÁLEZ; LÉGER, 2019Degeneration occurs mainly in areas responsible for language, memory, visual processing and executive functionsKNOPMAN; AMIEVA; PETERSEN; CHÉTELAT et al., 2021iagnosis is made difficult by the late onset of observable symptoms, which occur between 10 and 20 years after the onset of degenerationSPERLING; AISEN; BECKETT; BENNETT et al., 2011and the greatest risk factor for the development of the disease is age. There are still controversies regarding the causes of the disease, however, the most prevalent hypothesis is that the disease occurs from the accumulation of amyloid beta protein in the brainSELKOE, 2004Although Alzheimer's disease is the biggest cause of dementia, this condition can be triggered by other neurodegenerative pathologies, especially in the elderlyKAPASI; DECARLI; SCHNEIDER, 2017Furthermore, the prevalence of dementia is high and tends to increase further, from 50 million people in 2010 to 113 million people around the world in 2050BRODATY; BRETELER; DEKOSKY; DORENLOT et al., 2011Therefore, considering the debilitating characteristic of the disease and its high prevalence, the aim of this article is to elucidate the relationship between Alzheimer's disease and the sleep-wake cycle.  

Sleep and sleep-wake rhythm disorders are common in patients with Alzheimer's disease. These patients present imbalances in relation to the time of onset and duration of sleep, which is manifested through increased latency to sleep onset and time awake during the night, as well as sleep episodes during the light phase of the day that, with the passage of time, time, can generate inversion of the sleep phase of these patients. Through sleep architecture analysis, it is possible to observe that these patients present a reduction in the proportion of REM sleep compared to control individuals of the same age, leading to chronic restriction of REM sleepPETIT; GAGNON; FANTINI; FERINI-STRAMBI et al., 2004Not only, these patients also present a reduction in the proportion of slow wave sleepMARTIN; LOEWENSTEIN; KAYE; EBERT et al., 1986). 

These changes in the temporal organization and structure of sleep occur early in the course of the disease. There are studies in rats demonstrating that the deposition of amyloid beta protein causes changes in sleep architecture, sleep phase delay, altered nocturnal activity level and reduction of REM sleep. These effects were, in some cases, reversed after immunotherapy with beta amyloid, demonstrating the role that this protein plays in patientsROH; HUANG; BERO; KASTEN et al., 2012).  

Such disorders are aggravated by age, especially if these individuals have other medical conditions. This leads them to reduce physical activity levels, irregular meal times and, consequently, generate few stimuli for sleep-wake rhythm synchronization. Reinforcing this component, institutionalized patients often have low exposure to light and, ultimately, medications for depression, hypertension, and heart disease can lead to sleep-wake rhythm disturbancesJU; LUCEY; HOLTZMAN, 2014These factors amplify signals that negatively contribute to sleep quality and sleep-wake rhythm stability. 

On the other hand, there are studies demonstrating that sleep restriction and/or poor quality sleep are predisposing factors for the development of cognitive disordersFAUBEL; LÓPEZ-GARCÍA; GUALLAR-CASTILLÓN; GRACIANI et al., 2009A prospective study evaluated the sleep of volunteers using actigraphy and the results showed that sleep fragmentation increased the risk for developing Alzheimer's diseaseSTERNICZUK; THEOU; RUSAK; ROCKWOOD, 2013In both rats and humans, levels of soluble beta amyloid fluctuate throughout sleep-wake, so levels increase during wakefulness and decrease during sleep. Thus, acute sleep deprivation increases the concentration of beta amyloid and, in addition, chronic sleep restriction accelerates the deposition of beta amyloid in insoluble plaqueANCOLI-ISRAEL; COLE; ALESSI; CHAMBERS et al., 2003).  


Alzheimer's disease is an extremely debilitating condition for the individual, and in terms of sleep, evidence indicates that nighttime insomnia, nighttime restlessness and excessive daytime sleepiness affect 25-40% of patients with Alzheimer's disease, so that the intensity of these disorders correlates with the intensity of the disease. As already mentioned, circadian rhythms show a reduction in the amplitude of endogenous rhythms and phase delay of these rhythms, especially in advanced stages of the disease. Sleep disturbances occur early in the course of the disease, a fact that contributes to the advancement of the pathology. Thus, it is important that these patients are monitored and receive specific care, especially in relation to the assessment of biological rhythms and sleep disorders. 

How to assess the sleep of these patients 

Polysomnography is considered the gold standard for sleep assessment, however, the use of this method in patients with Alzheimer's disease is usually difficult because it requires patient cooperation and, in many cases, especially in advanced stages of the disease, patients cannot tolerate laboratory procedures. Similarly, the application of questionnaires such as thePittsburgh Sleep Quality Index – PSQI) have little practical value, as these patients tend to underestimate existing sleep and rhythm disturbances, even in early stages of the diseaseMOST; ABOUDAN; SCHELTENS; VAN SOMEREN, 2012leading to biased results  

Thus, actigraphy becomes a more suitable procedure to assess sleep and sleep-wake rhythm in these patients, as it is a less invasive technique. Actigraphy is a technique that can be used to assess sleep pattern and sleep-wake rhythm. The actigraph is a wristwatch-like device that contains light, motion, and temperature sensors. Thus, through this information, it is possible to extract data on variables such as total sleep time, sleep onset latency, time awake after sleep onset, sleep efficiency, time awake and variables related to rhythm, such as cosinor, spectrogram, periodogram, and non-parametric variables such as L5, M10, IS and IV.