Slow-wave sleep across the Alzheimer’s disease continuum: cognitive trajectories and sex differences
Year: 2026
Type: article
Study design: Observational Study
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.
Source: Alzheimer s Research & Therapy
Authors: Núria Tort-Colet, Ana Fernández-Arcos, Gerard Mayà, Laura Stankeviciute, Carolina Minguillon, Laura Hernández, Iva Knezevic, Natalia Soldevila-Domenech, Gonzalo Sanchez-Benavides, Michalis Kassinopoulos, Marc Suárez-Calvet, Sebastian C. Holst, Henrik Zetterberg, Kaj Blennow, Lea T. Grinberg, Amaia Muñoz-Lopetegi, Isabel Martín-Sobrino, Aurora Arqueros, Angelica Montini, Carles Gaig, Albert Lladó, Raquel Sánchez-Valle, Gerard Piñol-Ripoll, Andrea Val-Guardiola, Álex Iranzo, Juan Domingo Gispert, Jose Luis Molinuevo, Neus Falgàs, Oriol Grau-Rivera, for the ALFA study, Clara Abadías, Müge Akinci, Andrea Ambite, Federica Anastasi, Ricardo Aquite, Sara Aragó, Eider Arenaza Urquijo, Kahina Baouche, Ricardo Berbería, Annabella Beteta, Marco Bianchi, Helena Blasco, Anna Brugulat-Serrat, Raffaele Cacciaglia, Jordi Camí, Fernanda Campos Strazzi, Lidia Canals Gispert, Alba Cañas, Diego Cascales, José Contador, Marta Crous-Bou, Irene Cumplido, Rafael Dal-Ré, Marina de Diego, Neus de la Cruz-Sanchez, Marta del Campo, Carme Deulofeu, Ruth Dominguez, Maria Emilio, Isabel Estragués, Tavia Evans, Carles Falcón, Karine Fauria, Marta Félez, Aida Fernandez, Alba Fernández Bonet, Elisabeth Ferrer i Mairal, Jordi Freixa, Sherezade Fuentes, Clara Gallay, Marina García, Manuel Garfia, Fernando Gaston Rossi, Patricia Genius, José María González de Echávarri, Armand González-Escalante, Xavier Gotsens, Nina Gramunt Fombuena, Laura Gusó, Ana Harris, Felipe Hernández-Villamizar, Gema Huesa, Jordi Huguet, Laura Iglesias, Esther Jiménez, Maria León, Aldana Lizarraga, David López-Martos, Ferran Lugo, Paula Marne, Carlota Medina, Francisco Javier Meléndez, Tania Menchón, Marta Milà Alomà, Cristina Mustata, Irene Navalpotro, Grégory Operto, Paula Ortiz, Eva Palacios, Eleni Palpatzis, Wiesje Pelkmans, Jordi Peña-Casanova, Isabel Perez, Aitana Plaza, Albina Polo, Clara Porta, Sandra Pradas, Aleix Puig, Andreea Rădoi, Jaume Roca Alcaraz, Albert Rodrigo-Pares, Noelia Rodríguez de Guzmán Gallego, Blanca Rodríguez-Fernández, Maria Roman, Sarata Sall Sall, Gemma Salvadó, Mireia Sánchez, Pau Sánchez, Sabrina Segundo, Mahnaz Shekari, Lluis Solsona, Anna Soteras, Pilar Tartière-González, Laia Tenas, Javier Torres-Torronteras, Elisabet Zhan Travesset Muntada, David Vállez, Montserrat Vilà, Marc Vilanova, Natalia Vilor-Tejedor
Institutions: Instituto de Salud Carlos III, Pasqual Maragall Foundation, Barcelonaβeta Brain Research Center, Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable, Hospital del Mar Research Institute, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, University of Gothenburg, Hospital Del Mar, F. Hoffmann-La Roche AG, Sahlgrenska University Hospital, Mayo Clinic, Mayo Clinic in Florida, Biomedical Research Networking Center on Neurodegenerative Diseases, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine, Centro de Investigación Biomédica en Red, Lundbeck (Denmark)
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,290
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
Awards: Caracterización del sueño con medidas de actigrafía y orexina en LCR y su asociación con biomarcadores en enfermedad de Alzheimer preclínica, G2058760593, Implementación de un Servicio de Salud Cerebral para la Estratificación Personalizada y Prevención del Riesgo de Demencia: El Proyecto B-HEALTH, G3480869486, G3988176957, Novel Biomarkers Related to Sleep-Wake Alterations in Alzheimer’s disease, G5080475149, G6564880142, G7084143925, G7604509605, El impacto clínico de los nuevos biomarcadores sanguíneos de Alzheimer: el estudio PLASMAR, G8872466100
OpenAlex ID: W7165184127