Timely coupling of sleep spindles and slow waves is linked to early amyloid-β burden and predicts memory decline

Abstract

Sleep alteration is a hallmark of ageing and emerges as a risk factor for Alzheimer's disease (AD). While the fine-tuned coalescence of sleep microstructure elements may influence age-related cognitive trajectories, its association with AD processes is not fully established. Here, we investigated whether the coupling of spindles and slow waves is associated with early amyloid-beta (Aβ) brain burden, a hallmark of AD neuropathology, and cognitive change over 2 years in 100 healthy individuals in late-midlife (50-70y; 68 women). We found that, in contrast to other sleep metrics, earlier occurrence of spindles on slow-depolarisation slow waves is associated with higher medial prefrontal cortex Aβ burden (p=0.014, r²β*=0.06), and is predictive of greater longitudinal memory decline in a large subsample (p=0.032, r²β*=0.07, N=66). These findings unravel early links between sleep, AD-related processes and cognition and suggest that altered coupling of sleep microstructure elements, key to its mnesic function, contributes to poorer brain and cognitive trajectories in ageing.

Data availability

The data and analysis scripts supporting the results included in this manuscript are publicly available via the following open repository: https://gitlab.uliege.be/CyclotronResearchCentre/Public/fasst/slow-wave-spindle-coupling-and-amyloid. We used Matlab script for MRI and PET data processing and to detect slow waves and spindles as well as their coupling, while we used SAS for statistical analyses. The raw data could be identified and linked to a single subject and represent a huge amount of data (> 200 Gb). Researchers willing to access the raw data should send a request to the corresponding author (GV). Data sharing will require evaluation of the request by the Medicine Faculty-Hostpital Ethic Committee of the University of Liège, Belgium and the signature of a data transfer agreement (DTA).

Article and author information

Author details

  1. Daphne Chylinski

    GIGA-Cyclotron Research Centre-In Vivo Imaging, University of Liège, Liège, Belgium
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7319-0859
  2. Maxime Van Egroo

    GIGA-Cyclotron Research Centre-In Vivo Imaging, University of Liège, Liège, Belgium
    Competing interests
    No competing interests declared.
  3. Justinas Narbutas

    GIGA-Cyclotron Research Centre-In Vivo Imaging, University of Liège, Liège, Belgium
    Competing interests
    No competing interests declared.
  4. Vincenzo Muto

    GIGA-Cyclotron Research Centre-In Vivo Imaging, University of Liège, Liège, Belgium
    Competing interests
    No competing interests declared.
  5. Mohamed Ali Bahri

    GIGA-Cyclotron Research Centre-In Vivo Imaging, University of Liège, Liège, Belgium
    Competing interests
    No competing interests declared.
  6. Christian Berthomier

    Physip, Paris, France
    Competing interests
    Christian Berthomier, is an owner of Physip, the company that analysed the EEG data as part of a collaboration. This ownership and the collaboration had no impact on the design, data acquisition and interpretations of the findings..
  7. Eric Salmon

    GIGA-Cyclotron Research Centre-In Vivo Imaging, University of Liège, Liège, Belgium
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2520-9241
  8. Christine Bastin

    GIGA-Cyclotron Research Centre-In Vivo Imaging, University of Liège, Liège, Belgium
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4556-9490
  9. Christophe Phillips

    GIGA-Cyclotron Research Centre-In Vivo Imaging, University of Liège, Liège, Belgium
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4990-425X
  10. Fabienne Collette

    GIGA-Cyclotron Research Centre-In Vivo Imaging, University of Liège, Liège, Belgium
    Competing interests
    No competing interests declared.
  11. Pierre Maquet

    GIGA-Cyclotron Research Centre-In Vivo Imaging, University of Liège, Liège, Belgium
    Competing interests
    No competing interests declared.
  12. Julie Carrier

    Centre for Advanced Research in Sleep Medicine, Université de Montréal, Montreal, Canada
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5311-2370
  13. Jean-Marc Lina

    Centre for Advanced Research in Sleep Medicine, Université de Montréal, Montreal, Canada
    Competing interests
    No competing interests declared.
  14. Gilles Vandewalle

    GIGA-Cyclotron Research Centre-In Vivo Imaging, University of Liège, Liège, Belgium
    For correspondence
    gilles.vandewalle@uliege.be
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2483-2752

Funding

Fonds De La Recherche Scientifique - FNRS (FRSM 3.4516.11)

  • Gilles Vandewalle

Fédération Wallonie-Bruxelles (ARC-SLEEPDEM 17/09)

  • Daphne Chylinski
  • Maxime Van Egroo
  • Justinas Narbutas
  • Christine Bastin
  • Christophe Phillips
  • Fabienne Collette
  • Pierre Maquet
  • Gilles Vandewalle

European Regional Development Fund (RAdiomed)

  • Daphne Chylinski
  • Maxime Van Egroo
  • Justinas Narbutas
  • Vincenzo Muto
  • Mohamed Ali Bahri
  • Eric Salmon
  • Christine Bastin
  • Christophe Phillips
  • Fabienne Collette
  • Pierre Maquet
  • Gilles Vandewalle

Canadian Institutes of Health Research (grant number 190750)

  • Julie Carrier
  • Jean-Marc Lina

General Electric (ISS290)

  • Eric Salmon
  • Christine Bastin
  • Christophe Phillips
  • Fabienne Collette
  • Pierre Maquet
  • Gilles Vandewalle

Fonds De La Recherche Scientifique - FNRS

  • Maxime Van Egroo
  • Christine Bastin
  • Christophe Phillips
  • Fabienne Collette
  • Gilles Vandewalle

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The study was registered with EudraCT 2016-001436-35. All procedures were approved by the Hospital-Faculty Ethics Committee of ULiège. All participants signed an informed consent prior to participating in the study.

Reviewing Editor

  1. Sakiko Honjoh, University of Tsukuba, Japan

Publication history

  1. Received: February 26, 2022
  2. Preprint posted: March 19, 2022 (view preprint)
  3. Accepted: May 23, 2022
  4. Accepted Manuscript published: May 31, 2022 (version 1)
  5. Version of Record published: June 8, 2022 (version 2)

Copyright

© 2022, Chylinski et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Daphne Chylinski
  2. Maxime Van Egroo
  3. Justinas Narbutas
  4. Vincenzo Muto
  5. Mohamed Ali Bahri
  6. Christian Berthomier
  7. Eric Salmon
  8. Christine Bastin
  9. Christophe Phillips
  10. Fabienne Collette
  11. Pierre Maquet
  12. Julie Carrier
  13. Jean-Marc Lina
  14. Gilles Vandewalle
(2022)
Timely coupling of sleep spindles and slow waves is linked to early amyloid-β burden and predicts memory decline
eLife 11:e78191.
https://doi.org/10.7554/eLife.78191

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