Is Sleep Disruption a Cause or Consequence of Alzheimer’s Disease? Reviewing Its Possible Role as a Biomarker

Abstract

In recent years, the idea that sleep is critical for cognitive processing has gained strength. Alzheimer's disease (AD) is the most common form of dementia worldwide and presents a high prevalence of sleep disturbances. However, it is difficult to establish causal relations, since a vicious circle emerges between different aspects of the disease. Nowadays, we know that sleep is crucial to consolidate memory and to remove the excess of beta-amyloid and hyperphosphorilated tau accumulated in AD patients' brains. In this review, we discuss how sleep disturbances often precede in years some pathological traits, as well as cognitive decline, in AD. We describe the relevance of sleep to memory consolidation, focusing on changes in sleep patterns in AD in contrast to normal aging. We also analyze whether sleep alterations could be useful biomarkers to predict the risk of developing AD and we compile some sleep-related proposed biomarkers. The relevance of the analysis of the sleep microstructure is highlighted to detect specific oscillatory patterns that could be useful as AD biomarkers.the risk of developing AD [9]. Similarly, Bubu and colleagues estimated in a meta-analysis that the risk of dementia in patients with sleep disorders was 1.68 times greater [10]. Moreover, in a recent multi-center study, both midlife and late-life terminal insomnia were associated with a higher risk of dementia [11].It is interesting to note that affected brain structures in people with disturbed sleep coincide with vulnerable areas in AD. Lower gray matter volume in hippocampus, precuneus, amygdala, and cingulate gyrus [12][13][14][15][16][17][18][19], and a higher degree of cortical atrophy have been described in cognitively-unimpaired insomnia patients [14,20]. A recent study performed in cognitively unimpaired adults aged between 45 and 75, found that insomnia patients presented decreases in grey matter volume in AD-related areas, that concur with other studies. Furthermore, they found greater volume in the left caudate in these subjects, which can also be seen in presymptomatic carriers of an AD genetic mutation [21]. Finally, a very recent study in middle-aged, cognitively unimpaired adults found lower grey matter volumes in the left angular gyrus, the bilateral superior frontal gyri, the thalami, and the right hippocampus in insomniac APOE-ε4 carriers (AD's main risk factor) when compared to non-carriers with or without insomnia [21].This temporal and anatomical relationship could suggest that sleep disturbances may influence or exacerbate AD pathology and that improving sleep may help slow down its progression [22,23]. Additionally, sleep alterations could be used to predict the risk of developing dementia and could also serve as early indicators of the disease. If sleep disorders constitute a risk factor to initiate or to accelerate the clinical course of AD, they could be used to develop disease biomarkers. Furthermore, a sleep biomarker with high sensitivity and specificity would be extremely useful, as electrophysiological re...

Sleep disturbances and dementia risk: A multicenter study

“…For example, recent cross-sectional studies suggest that SWS may be more related to Aβ (Mander et al, 2015), while spindle coupling may be more related to tau pathology (Winer et al, 2019). Therefore, it has been suggested that sleep itself could be used as an early marker of preclinical AD (Hita-Yanez et al, 2013;Jelicic et al, 2002;Ju et al, 2013;Lloret et al, 2020;Winer et al, 2019). Assessing sleep is a relatively non-invasive method in comparison with CSF or PET scans.…”

Sleep-Wake Disturbances and Episodic Memory in Older Adults

“…Scientific evidence supports the relationship between sleep-wake disturbances and episodic memory (Inostroza & Born, 2013; Lloret et al, 2020). Sleep promotes the consolidation of episodic memory by the replaying of neural activities occurring in the hippocampal and extrahippocampal regions, including the neocortical and striatal networks during sleep.…”

“…Sleep promotes the consolidation of episodic memory by the replaying of neural activities occurring in the hippocampal and extrahippocampal regions, including the neocortical and striatal networks during sleep. Sleep-wake disturbances may disrupt consolidation because they interrupt neural reactivation in the hippocampal and extrahippocampal regions (Inostroza & Born, 2013; Lloret et al, 2020). One reason the relationship between sleep-wake disturbance and episodic memory loss in older adults is equivocal is because studies have used exclusively objective or perceived measures of sleep-wake disturbances (Yeh et al, 2018), which may impede fully understanding of sleep-wake disturbances.…”

Sleep Disturbance, Sleep Disorders and Co-Morbidities in the Care of the Older Person

“…There also appears to be a bi-directional relationship between dementia and sleep, with sleep disruption representing both a risk factor for, and symptom of, the neurocognitive syndrome [233][234][235]. A recent systematic review and metanalysis found that sleep problems, including both short and long sleep duration, insomnia, OSA, impaired circadian rhythm and sleep quality, were associated with an increased relative risk of preclinical AD, cognitive impairment and AD [236].…”