Self-reported sleep quality and longitudinal amyloid burden in clinically unimpaired adults from the AMYPAD PNHS study

Poor self-reported sleep quality is associated with cognitive impairment. Alzheimer’s disease (AD) patients present sleep disruptions decades before they start to decline clinically. Similarly, amyloid-β (Aβ) starts accumulating during the preclinical phase of the disease. This study investigated associations between self-reported sleep quality and Aβ burden longitudinally in clinically unimpaired (CU) adults. Four hundred seventeen CU adults from the AMYPAD PNHS cohort were included, with baseline self-reported sleep quality assessments (Pittsburgh Sleep Quality Index, PSQI) and longitudinal Aβ PET scans. Participants were categorized by baseline Aβ levels as negative (A-), grey-zone (GZ), or positive (A+). Linear mixed-effects (LME) models tested the association between baseline sleep quality and Aβ burden over time, including interaction effects with baseline Aβ status. Global PSQI score was not associated with Aβ burden over time in the entire group. However, a significant interaction with baseline Aβ status was found, whereby poorer subjective sleep quality was linked to accelerated Aβ accumulation in GZ participants. Poorer subjective sleep quality is associated with faster Aβ accumulation in CU individuals with intermediate Aβ levels, highlighting sleep as a potential target for early AD prevention and identifying an optimal intervention window.

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Publication Details

Journal
Alzheimer s Research & Therapy
Published
2026-04-17
DOI
https://doi.org/10.1186/s13195-026-02049-w
Primary Topic
Sleep and related disorders
Type
article
Field-Weighted Citation Impact
0.00

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article

Self-reported sleep quality and longitudinal amyloid burden in clinically unimpaired adults from the AMYPAD PNHS study

Emma S. Luckett, Rossella Gismondi, David Vállez García, Bernard Hanseeuw et al.
Alzheimer s Research & Therapy
Sleep and related disorders
article

Self-reported sleep quality and longitudinal amyloid burden in clinically unimpaired adults from the AMYPAD PNHS study

Emma S. Luckett, Rossella Gismondi, David Vállez García, Bernard Hanseeuw, Lisa Quenon, Anja Mett, Daniele Altomare, Ana Fernández‐Arcos, Gill Farrar, Laura Stankeviciute, Mark E. Schmidt, S. Grootoonk, Richard Manber, Juan D. Gispert, F Jessen, Robin Wolz, Lisa Ford, Natalia Soldevila-Domenech, Rik Vandenberghe, Lyduine E. Collij, Mahnaz Shekari, Giovanni B. Frisoni, Michael Schöll, Christopher Buckley, Marta Marquié, Oriol Grau-Rivera, Anouk den Braber, Andrew W. Stephens, Gonzalo Sánchez-Benavides, Núria Tort-Colet, Craig Ritchie, Frederik Barkhof, Mercè Boada, Pieter J. Visser
article en

Abstract

Poor self-reported sleep quality is associated with cognitive impairment. Alzheimer’s disease (AD) patients present sleep disruptions decades before they start to decline clinically. Similarly, amyloid-β (Aβ) starts accumulating during the preclinical phase of the disease. This study investigated associations between self-reported sleep quality and Aβ burden longitudinally in clinically unimpaired (CU) adults. Four hundred seventeen CU adults from the AMYPAD PNHS cohort were included, with baseline self-reported sleep quality assessments (Pittsburgh Sleep Quality Index, PSQI) and longitudinal Aβ PET scans. Participants were categorized by baseline Aβ levels as negative (A-), grey-zone (GZ), or positive (A+). Linear mixed-effects (LME) models tested the association between baseline sleep quality and Aβ burden over time, including interaction effects with baseline Aβ status. Global PSQI score was not associated with Aβ burden over time in the entire group. However, a significant interaction with baseline Aβ status was found, whereby poorer subjective sleep quality was linked to accelerated Aβ accumulation in GZ participants. Poorer subjective sleep quality is associated with faster Aβ accumulation in CU individuals with intermediate Aβ levels, highlighting sleep as a potential target for early AD prevention and identifying an optimal intervention window.

Alzheimer s Research & Therapy
University of Geneva (CH), Cliniques Universitaires Saint-Luc (BE), Johnson & Johnson (United States) (US), Janssen (Belgium) (BE), University of Applied Sciences and Arts of Southern Switzerland (CH), University of Cologne (DE), Lund University (SE), General Electric (Spain) (ES), Amersham Hospital (GB), Instituto de Salud Carlos III (ES), German Center for Neurodegenerative Diseases (DE), Universitat Internacional de Catalunya (ES), Maastricht University (NL), Biomedical Research Networking Center on Neurodegenerative Diseases (ES), Ixico (United Kingdom) (GB), Center for Human Genetics (US), University Hospital of Geneva (CH), Pasqual Maragall Foundation (ES), Amsterdam Neuroscience (NL), UK Dementia Research Institute (GB), Barcelonaβeta Brain Research Center (ES), Hospital Del Mar (ES), Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (ES), National Hospital for Neurology and Neurosurgery (GB), Amsterdam University Medical Centers (NL), ABT Molecular Imaging (United States) (US), University College London (GB), Vrije Universiteit Amsterdam (NL), University of Gothenburg (SE), UCLouvain (BE), University of Edinburgh (GB), KU Leuven (BE)
Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III
No poverty
Openalex Percentile: Top 17%
Sleep and related disorders
DOIOpen Access PDFOpenAlex
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