- Academic Editor
The relationship between sleep and Alzheimer’s disease (AD) has become
increasingly apparent in recent years with the results of new scientific
investigations and with AD being viewed as a multidimensional disease. One of the
aims of researchers and clinicians is to identify AD biomarkers in the
preclinical phase of the disease. The histopathological signs of AD during this
phase (e.g., deposition of insoluble plaques of extracellular beta amyloid
(A
The main neuropathological events that characterize AD are evident during the
preclinical stage. Changes in sleep patterns are closely related to the
accumulation of A
The relationship between sleep and AD is bidirectional, with the two conditions influencing each other [4]. The most promising research topics in this field are: (i) the study of mechanisms that could explain how sleep promotes or reduces the risk of AD; (ii) the effects of sleep deprivation on features related to AD; (iii) the role of Obstructive Sleep Apnoea Syndrome (OSAS); (iv) the role of slow wave sleep (SWS) in relation to AD; (v) the relationship between sleep electroencephalographic (EEG) components and the neuropathological and cognitive characteristics of AD; and (vi) the implementation of sleep-based treatments in elderly, MCI and AD patients.
With regard to the mechanisms by which sleep could promote AD, many studies have
shown that A
Variations in the sleep-wake cycle, together with increased A
Many of the novel concepts regarding the relationship between sleep and AD are
derived from longitudinal studies employing different sleep deprivation
protocols, in association with different subtypes of cognitive impairment. Sleep
deprivation generally increases tau levels in the interstitial fluid (ISF) of
mouse brain and in the CSF of humans, while chronic deprivation accelerates the
spread of aggregated tau in specific brain networks
[2]. The importance of sleep deprivation is highlighted by the recent discovery
that sleep plays a role in clearing the brain of toxic metabolic by-products,
including A
The role of sleep in clearing A
What happens to the specific EEG components of NREM? Both K-complexes and spindles undergo changes in healthy elderly, MCI and AD populations. Furthermore, these alterations are associated with changes in cognition and with structural integrity of the brain. K-complexes react to external stimuli during sleep, and protect sleep during the essential synchronisation part of NREM. These decrease significantly in AD/MCI patients and also correlate positively with global cognitive status scores [12]. At a frequency range of 13–15 Hz, fast spindles (EEG features of NREM related to cognition and sleep-dependent memory consolidation) decrease in association with learning and memory abilities [10]. They are also negatively associated with the structural integrity of the brain (reduction in hippocampal subcortical grey matter) that predicts the extent of the reduction in frontal lobe spindle density in the elderly [13].
The different emerging dimensions on the commonalities between sleep and AD make it difficult to suggest specific sleep-based interventions. Sleep assessment should be routinely included in at-risk populations, in the pre-clinical phases of the disease, and in the diagnostic phase in MCI and AD. In order to develop therapeutic strategies, it is important to distinguish between different sleep-related problems and to implement targeted interventions according to patient characteristics. In general, the sleep-based treatments considered to be effective for healthy elderly and MCI/AD patients are sleep hygiene guidelines, combined interventions, and bright light therapy (BLT). Another promising therapeutic approach may also be direct modulation of NREM sleep electrophysiology, with different targets for specific AD phases. Several non-invasive techniques (Transcranial Current Stimulation, tCS; and repetitive Transcranial Magnetic Stimulation, rTMS) are able to modulate EEG oscillations during sleep and could have beneficial effects on memory [14].
The current research findings on the importance of sleep in relation to normal and pathological ageing still need to be translated into improved clinical practice. Longitudinal studies on adults and elderly populations are expected to continue, with increasingly structured integration of electrophysiological, anatomical, neuropsychological and clinical data. Future research should deepen the mechanisms linking sleep and AD and test the efficacy of sleep-based interventions on large populations of healthy subjects and MCI/AD patients.
LG and SC wrote the manuscript and conducted a literature review. Both authors read and approved the final manuscript.
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This research received no external funding.
The authors declare no conflict of interest. Luigi De Gennaro is serving as one of the Editorial Board members. We declare that Luigi De Gennaro had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Gernot Riedel.
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