Sleep disorders and Alzheimer's disease pathophysiology: The role of the Glymphatic System. A scoping review

Kyriaki Astara; Alexandros Tsimpolis; Konstantinos Kalafatakis; George D Vavougios; Georgia Xiromerisiou; Efthimios Dardiotis; Nikos G Christodoulou; Myrto T Samara; Andreas S Lappas

doi:10.1016/j.mad.2023.111899

Sleep disorders and Alzheimer's disease pathophysiology: The role of the Glymphatic System. A scoping review

Mech Ageing Dev. 2024 Feb:217:111899. doi: 10.1016/j.mad.2023.111899. Epub 2023 Dec 30.

Authors

Kyriaki Astara¹, Alexandros Tsimpolis², Konstantinos Kalafatakis³, George D Vavougios⁴, Georgia Xiromerisiou⁵, Efthimios Dardiotis⁵, Nikos G Christodoulou⁶, Myrto T Samara⁷, Andreas S Lappas⁸

Affiliations

¹ Department of Psychiatry, Faculty of Medicine, University of Thessaly, Larissa, Greece; Department of Neurology, 417 Army Equity Fund Hospital (NIMTS), Athens, Greece.
² Department of Pharmacology, Medical School, University of Crete & Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology Hellas, Heraklion, Crete, Greece.
³ Faculty of Medicine & Dentistry (Malta campus), Queen Mary University of London, VCT 2520, Victoria, Gozo, Malta. Electronic address: k.kalafatakis@qmul.ac.uk.
⁴ Department of Neurology, Faculty of Medicine, University of Cyprus, Lefkosia, Cyprus; Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, Larissa, Greece; Department of Neurology, Athens Naval Hospital, Athens, Greece.
⁵ Department of Neurology, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41110 Larissa, Greece.
⁶ Department of Psychiatry, Faculty of Medicine, University of Thessaly, Larissa, Greece; Medical School, University of Nottingham, Lenton, Nottingham, UK.
⁷ Department of Psychiatry, Faculty of Medicine, University of Thessaly, Larissa, Greece.
⁸ Department of Psychiatry, Faculty of Medicine, University of Thessaly, Larissa, Greece; Aneurin Bevan University Health Board, Wales, UK.

PMID: 38163471
DOI: 10.1016/j.mad.2023.111899

Abstract

Background: Alzheimer's disease (AD) is highly intertwined with sleep disturbances throughout its whole natural history. Sleep consists of a major compound of the functionality of the glymphatic system, as the synchronized slow-wave activity during NREM facilitates cerebrospinal and interstitial long-distance mixing.

Objective: The present study undertakes a scoping review of research on the involvement of the glymphatic system in AD-related sleep disturbances.

Design: we searched Medline, Embase, PsychInfo and HEAL-link databases, without limitations on date and language, along with reference lists of relevant reviews and all included studies. We included in vivo, in vitro and post-mortem studies examining glymphatic implications of sleep disturbances in human populations with AD spectrum pathology. A thematic synthesis of evidence based on the extracted content was applied and presented in a narrative way.

Results: In total, 70 original research articles were included and were grouped as following: a) Protein aggregation and toxicity, after sleep deprivation, along with its effects on sleep architecture, b) Glymphatic Sequalae in SDB, yielding potential glymphatic markers c) Circadian Dysregulation, d) Possible Interventions.

Conclusions: this review sought to provide insight into the role of sleep disturbances in AD pathogenesis, in the context of the glymphatic disruption.

Keywords: Alzheimer's disease; Glymphatic system; Sleep disturbances.

Publication types

Review

MeSH terms

Alzheimer Disease* / metabolism
Brain / metabolism
Glymphatic System* / metabolism
Humans
Sleep / physiology
Sleep Deprivation
Sleep Wake Disorders* / metabolism