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.
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).
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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.
© 2022, Chylinski et al.
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