Slow-wave sleep across the Alzheimer’s disease continuum: cognitive trajectories and sex differences
Abstract Background Sleep disturbances are common in Alzheimer's disease and have been reported in its preclinical stage. A detailed characterization of sleep disruption across the Alzheimer’s disease continuum is required to clarify its role as a potential therapeutic target and to evaluate the utility of sleep-related biomarkers. Methods Sleep architecture was characterized through detailed spectral and temporal analysis of the slow-wave activity using polysomnography across the Alzheimer’s disease continuum . Participants included: cognitively unimpaired individuals without abnormal Alzheimer’s disease biomarkers (n = 30), cognitively unimpaired individuals with abnormal Alzheimer’s disease biomarkers (n = 45), and individuals with mild cognitive impairment or mild dementia due to Alzheimer’s disease (n = 41). Associations between slow-wave features and longitudinal cognitive performance were tested in cognitively unimpaired participants. Sex differences were also explored. Results A stepwise increased wake after sleep onset and latency to rapid eye movement sleep was observed, alongside reduced spectral power of slow-wave activity and a progressive flattening of slow-waves across the Alzheimer’s disease continuum in both sexes. In cognitively unimpaired individuals, higher slow-wave slope and greater peak-to-peak amplitude were associated with better cognitive trajectories over time. Conclusions Sleep macro- and microarchitecture are altered early and progressively deteriorate across the Alzheimer’s disease continuum . Slow-wave features relate to cognitive trajectories in preclinical Alzheimer’s disease, with exploratory analyses suggesting stronger associations in men. These findings support slow-wave morphology as a candidate non-invasive marker for future sleep-based intervention studies.
Authors
- Núria Tort‐Colet (ORCID: https://orcid.org/0000-0002-9708-9755)
- Lea T. Grinberg (ORCID: https://orcid.org/0000-0002-6809-0618)
- Neus Falgàs (ORCID: https://orcid.org/0000-0002-3404-2765)
- Amaia Muñoz‐Lopetegi (ORCID: https://orcid.org/0000-0002-8852-0187)
- Aurora Arqueros
- Natalia Soldevila‐Domenech (ORCID: https://orcid.org/0000-0001-6024-8508)
- Gonzalo Sánchez‐Benavides (ORCID: https://orcid.org/0000-0003-3454-800X)
- Albert Lladó (ORCID: https://orcid.org/0000-0002-5066-4150)
- Kaj Blennow (ORCID: https://orcid.org/0000-0002-1890-4193)
- José Luís Molinuevo (ORCID: https://orcid.org/0000-0003-0485-6001)
- Sebastian C. Holst (ORCID: https://orcid.org/0000-0003-3657-4535)
- Angelica Montini (ORCID: https://orcid.org/0000-0001-5625-8850)
- Gerard Piñol‐Ripoll (ORCID: https://orcid.org/0000-0002-4495-2113)
- Iva Knezevic
- Raquel Sánchez‐Valle (ORCID: https://orcid.org/0000-0001-7750-896X)
- Juan Domingo Gispert (ORCID: https://orcid.org/0000-0002-6155-0642)
- Gerard Mayà (ORCID: https://orcid.org/0000-0002-5025-2615)
- Ana Fernández‐Arcos
- Oriol Grau‐Rivera (ORCID: https://orcid.org/0000-0002-4730-5341)
- Henrik Zetterberg (ORCID: https://orcid.org/0000-0003-3930-4354)
- Laura S Stankeviciute (ORCID: https://orcid.org/0000-0002-6601-3336)
- Michalis Kassinopoulos (ORCID: https://orcid.org/0000-0003-4312-4401)
- Marc Suárez‐Calvet (ORCID: https://orcid.org/0000-0002-2993-569X)
- Carolina Minguillón (ORCID: https://orcid.org/0000-0002-2782-6908)
- Carles Gaig (ORCID: https://orcid.org/0000-0002-7113-8125)
- Andrea Val‐Guardiola
- Alfa Study
- Álex Iranzo (ORCID: https://orcid.org/0000-0002-5618-8271)
- Isabel Martín-Sobrino (ORCID: https://orcid.org/0000-0002-7019-1688)
- Laura Hernández
Institutions
- F. Hoffmann-La Roche AG (CH)
- Mayo Clinic (US)
- Lundbeck (Denmark) (DK)
- Sahlgrenska University Hospital (SE)
- Instituto de Salud Carlos III (ES)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (ES)
- Pasqual Maragall Foundation (ES)
- Centro de Investigación Biomédica en Red (ES)
- Hospital Clínic de Barcelona (ES)
- Barcelonaβeta Brain Research Center (ES)
- Hospital Del Mar (ES)
- Mayo Clinic in Florida (US)
- Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (ES)
- Hospital del Mar Research Institute (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Universitat de Barcelona (ES)
- University of Gothenburg (SE)
Publication Details
- Journal
- Alzheimer s Research & Therapy
- Published
- 2026-11-09
- DOI
- https://doi.org/10.1186/s13195-026-02249-4
- Primary Topic
- Dementia and Cognitive Impairment Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Alzheimer's Association
- Eli Lilly and Company
- Biogen
- F. Hoffmann-La Roche
- Fundación BBVA
- Prothena
- Centres de Recerca de Catalunya
- European Commission
- Generalitat de Catalunya
- Novo Nordisk
- Banco Bilbao Vizcaya Argentaria
- Grifols
- Avid Radiopharmaceuticals
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Instituto de Salud Carlos III
- Agencia Estatal de Investigación