Sleep in Alzheimer’s disease: a systematic review and meta-analysis of polysomnographic findings

Zhang, Ye; Ren, Rong; Yang, Linghui; Zhang, Haipeng; Shi, Yuan; Okhravi, Hamid; Vitiello, Michael V.; Sanford, Larry D.; Tang, Xiangdong

doi:10.1038/s41398-022-01897-y

Cited by 72 publications

(34 citation statements)

References 88 publications

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“…This was comparable to those who were cognitively normal. Corroborating the consensus findings in AD, 8 we show that SWS is reduced in AD patients, but without seeing reductions in REM. Our findings address the limitations of PSG, especially cost, availability, and the need to spend a night in a hospital bed, while also addressing the main limitation of home EEG related to increased variability in data quality in the less controlled home environment.…”

Section: Discussionsupporting

confidence: 85%

“…While most sleep disorders are addressed symptomatically, more recent studies are addressing biological links by which sleep disturbances directly impact AD pathophysiology, especially levels of brain amyloid beta (Aβ) and tau 3–7 . A number of small studies using laboratory polysomnography (PSG) testing in AD have reported reduced slow‐wave sleep (SWS) and rapid eye movement (REM) sleep, 8 both of which are potential sleep therapeutic targets. As the gold standard, PSG affords the highest quality sleep staging information, but with the major drawbacks of high cost, limited availability, and the requirement to spend a night in a clinic bed, with inherent risks to persons with dementia who do not respond well to a change in environment.…”

Section: Introductionmentioning

confidence: 99%

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Home EEG sleep assessment shows reduced slow‐wave sleep in mild–moderate Alzheimer's disease

Kent

Casciola

Carlucci

et al. 2022

A&D Transl Res & Clin Interv

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Introduction: Sleep disturbances are common in Alzheimer's disease (AD), with estimates of prevalence as high as 65%. Recent work suggests that specific sleep stages, such as slow-wave sleep (SWS) and rapid eye movement (REM), may directly impact AD pathophysiology. A major limitation to sleep staging is the requirement for clinical polysomnography (PSG), which is often not well tolerated in patients with dementia.We have recently developed a deep learning model to reliably analyze lower quality electroencephalogram (EEG) data obtained from a simple, two-lead EEG headband.Here we assessed whether this methodology would allow for home EEG sleep staging in patients with mild-moderate AD.Methods: A total of 26 mild-moderate AD patients and 24 age-matched, healthy control participants underwent home EEG sleep recordings as well as actigraphy and subjective sleep measures through the Pittsburgh Sleep Quality Index (PSQI). Each participant wore the EEG headband for up to three nights. Sleep was staged using a deep learning model previously developed by our group, and sleep stages were correlated with actigraphy measures as well as PSQI scores. Results:We show that home EEG with a headband is feasible and well tolerated in patients with AD. Patients with mild-moderate AD were found to spend less time in SWS compared to healthy control participants. Other sleep stages were not different between the two groups. Actigraphy or the PSQI were not found to predict home EEG sleep stages. Discussion: Our data show that home EEG is well tolerated, and can ascertain reduced SWS in patients with mild-moderate AD. Similar findings have previously been reported, but using clinical PSG not suitable for the home environment. Home EEG will be particularly useful in future clinical trials assessing potential interventions that may target specific sleep stages to alter the pathogenesis of AD.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Home EEG sleep assessment shows reduced slow‐wave sleep in mild–moderate Alzheimer's disease

Kent

Casciola

Carlucci

et al. 2022

A&D Transl Res & Clin Interv

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“… 4 , 5 Dysfunction of the sleep cycle in AD features sleep fragmentation with shorter slow‐wave sleep (SWS‐N3), excessive daytime sleepiness (EDS), and sundowning. 6 EDS is also associated with impaired cognitive functions in elderly individuals and patients with mild cognitive impairment. 7 Measurement of non‐rapid eye movement (NREM), slow wave activity (SWA), and sleep quality may predict the rate of Aβ and tau accumulation in the cortex.…”

Section: Introductionmentioning

confidence: 99%

“…Sleep cycle disturbances are a common symptom in the early stages of AD, 3 and epidemiological studies have shown a link between sleep problems and dementia 4,5 . Dysfunction of the sleep cycle in AD features sleep fragmentation with shorter slow‐wave sleep (SWS‐N3), excessive daytime sleepiness (EDS), and sundowning 6 . EDS is also associated with impaired cognitive functions in elderly individuals and patients with mild cognitive impairment 7 .…”

Section: Introductionmentioning

confidence: 99%

Histaminergic neurotransmission in aging and Alzheimer's disease: A review of therapeutic opportunities and gaps

Satpati

Neylan

Grinberg

2023

A&D Transl Res & Clin Interv

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Introduction Alzheimer's disease (AD) is a progressive neurodegenerative disorderfeaturing a brain accumulation of extracellular β‐amyloidplaques (Aβ) and intracellular neurofibrillary tautangles (NFTs). Although cognitive decline is a disease‐defining symptom of AD, sleep dysfunction, a common symptom often preceding cognitive decline, hasrecently gained more attention as a core AD symptom. Polysomnography and othersleep measures show sleep fragmentation with shortening of N3 sleep togetherwith excessive daytime sleepiness (EDS) and sundowning as the main findings in AD patients. The latter reflects dysfunction of the wake‐promoting neurons (WPNs), including histaminergic neurons (HAN) located in thetuberomammillary nucleus (TMN) of the posterior hypothalamus, which projectunmyelinated axons to various parts of the brain. Histamine's role in cognitionand arousal is broadly recognized. Selective targeting of histaminergic subtype‐3 and 4 receptors show therapeutic potential in rodent models of AD andaging. Method Based on PubMed, Scopus, and google scholar databases search, this review summarizes the current knowledge on the histaminergic system in AD and aging, its therapeutic potential in AD, and highlight areas where moreresearch is needed. Results Animal studies have demonstrated that pharmacological manipulation of histaminergic receptors or histamine supplementation improves cognition in AD models. However, measurements of HA or HA metabolite levels in the human brainand CSF present contradictory reports due to either lack of power or controls for known confounders. Discussion Systemic studies including broad age, sex, neuropathological diagnosis, and disease stage are warranted to fill the gap in our current understanding of the histaminergic neurotransmitter/neuromodulator system in humans, especially age‐related changes, and therapeuticpotential of histamine in AD‐related dysfunction.

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“… 44 Finally, alterations in REM-sleep duration, latency and synchrony have been reported in AD probably due to degeneration of basal forebrain cholinergic nuclei. 45 46 However, the potential diagnostic usefulness of REM and NREM-sleep alterations in preclinical AD remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Exploring cognitive and biological correlates of sleep quality and their potential links with Alzheimer’s disease (ALFASleep project): protocol for an observational study

et al. 2022

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IntroductionThe growing worldwide prevalence of Alzheimer’s disease (AD) and the lack of effective treatments pose a dire medical challenge. Sleep disruption is also prevalent in the ageing population and is increasingly recognised as a risk factor and an early sign of AD. The ALFASleep project aims to characterise sleep with subjective and objective measurements in cognitively unimpaired middle/late middle-aged adults at increased risk of AD who are phenotyped with fluid and neuroimaging AD biomarkers. This will contribute to a better understanding of the pathophysiological mechanisms linking sleep with AD, thereby paving the way for the development of non-invasive biomarkers and preventive strategies targeting sleep.Methods and analysisWe will invite 200 participants enrolled in the ALFA+ (for ALzheimer and FAmilies) prospective observational study to join the ALFASleep study. ALFA+ participants are cognitively unimpaired middle-aged/late middle-aged adults who are followed up every 3 years with a comprehensive set of evaluations including neuropsychological tests, blood and cerebrospinal fluid (CSF) sampling, and MRI and positron emission tomography acquisition. ALFASleep participants will be additionally characterised with actigraphy and CSF–orexin-A measurements, and a subset (n=90) will undergo overnight polysomnography. We will test associations of sleep measurements and CSF–orexin-A with fluid biomarkers of AD and glial activation, neuroimaging outcomes and cognitive performance. In case we found any associations, we will test whether changes in AD and/or glial activation markers mediate the association between sleep and neuroimaging or cognitive outcomes and whether sleep mediates associations between CSF–orexin-A and AD biomarkers.Ethics and disseminationThe ALFASleep study protocol has been approved by the independent Ethics Committee Parc de Salut Mar, Barcelona (2018/8207/I). All participants have signed a written informed consent before their inclusion (approved by the same ethics committee). Study findings will be presented at national and international conferences and submitted for publication in peer-reviewed journals.Trial registration numberNCT04932473.

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Sleep in Alzheimer’s disease: a systematic review and meta-analysis of polysomnographic findings

Cited by 72 publications

References 88 publications

Home EEG sleep assessment shows reduced slow‐wave sleep in mild–moderate Alzheimer's disease

Home EEG sleep assessment shows reduced slow‐wave sleep in mild–moderate Alzheimer's disease

Histaminergic neurotransmission in aging and Alzheimer's disease: A review of therapeutic opportunities and gaps

Exploring cognitive and biological correlates of sleep quality and their potential links with Alzheimer’s disease (ALFASleep project): protocol for an observational study

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