Cross-sectional and longitudinal association of sleep and Alzheimer biomarkers in cognitively unimpaired adults

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• dc.contributor.author Blackman, Jonathan
• dc.contributor.author Stankeviciute, Laura
• dc.contributor.author Arenaza Urquijo, Eider M.
• dc.contributor.author Suárez-Calvet, Marc
• dc.contributor.author Sánchez Benavides, Gonzalo
• dc.contributor.author Vilor Tejedor, Natàlia, 1988-
• dc.contributor.author Iranzo, Alejandro
• dc.contributor.author Molinuevo, José Luis
• dc.contributor.author Gispert López, Juan Domingo
• dc.contributor.author Coulthard, Elizabeth
• dc.contributor.author Grau-Rivera, Oriol
• dc.contributor.author European Prevention of Alzheimer’s Disease (EPAD) Consortium
• dc.date.accessioned 2023-02-23T07:03:33Z
• dc.date.available 2023-02-23T07:03:33Z
• dc.date.issued 2022
• dc.description.abstract Sleep abnormalities are prevalent in Alzheimer's disease, with sleep quality already impaired at its preclinical stage. Epidemiological and experimental data point to sleep abnormalities contributing to the risk of Alzheimer's disease. However, previous studies are limited by either a lack of Alzheimer's disease biomarkers, reduced sample size or cross-sectional design. Understanding if, when, and how poor sleep contributes to Alzheimer's disease progression is important so that therapies can be targeted to the right phase of the disease. Using the largest cohort to date, the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study, we test the hypotheses that poor sleep is associated with core Alzheimer's disease CSF biomarkers cross-sectionally and predicts future increments of Alzheimer's disease pathology in people without identifiable symptoms of Alzheimer's disease at baseline. This study included 1168 adults aged over 50 years with CSF core Alzheimer's disease biomarkers (total tau, phosphorylated tau and amyloid-beta), cognitive performance, and sleep quality (Pittsburgh sleep quality index questionnaire) data. We used multivariate linear regressions to analyse associations between core Alzheimer's disease biomarkers and the following Pittsburgh sleep quality index measures: total score of sleep quality, binarized score (poor sleep categorized as Pittsburgh sleep quality index > 5), sleep latency, duration, efficiency and disturbance. On a subsample of 332 participants with CSF taken at baseline and after an average period of 1.5 years, we assessed the effect of baseline sleep quality on change in Alzheimer's disease biomarkers over time. Cross-sectional analyses revealed that poor sleep quality (Pittsburgh sleep quality index total > 5) was significantly associated with higher CSF t-tau; shorter sleep duration (<7 h) was associated with higher CSF p-tau and t-tau; and a higher degree of sleep disturbance (1-9 versus 0 and >9 versus 0) was associated with lower CSF amyloid-beta. Longitudinal analyses showed that greater sleep disturbances (1-9 versus 0 and >9 versus 0) were associated with a decrease in CSF Aβ42 over time. This study demonstrates that self-reported poor sleep quality is associated with greater Alzheimer's disease-related pathology in cognitively unimpaired individuals, with longitudinal results further strengthening the hypothesis that disrupted sleep may represent a risk factor for Alzheimer's disease. This highlights the need for future work to test the efficacy of preventive practices, designed to improve sleep at pre-symptomatic stages of disease, on reducing Alzheimer's disease pathology.
• dc.description.sponsorship O.G.-R. receives funding from the Alzheimer’s Association Research Fellowship Program (2019-AARF-644568). J.D.G. is supported by the Spanish Ministry of Science and Innovation (RYC-2013-13054). M.S.-C. receives funding from Instituto de Salud Carlos III (PI19/00155) and from the Spanish Ministry of Science, Innovation and Universities (Juan de la Cierva programme grant IJC2018-037478-I). N.V.-T. is funded by a Spanish Ministry of Science, Innovation and Universities postdoctoral grant (Juan de la Cierva programmegrant FJC2018-038085-I). E.M.A.-U. holds a ‘Ramón y Cajal’ fellowship (RYC2018-026053-I) and a grant of the Ministry of Science and Innovation (PID2019-111514RA-I00). J.B. receives funding from Alzheimer’s Research UK (supported by the Margaret Jost Fellowship and the Don Thoburn Memorial Scholarship) and the David Telling Charitable Trust, and E.C. has received funding from BRACE and ARUK (Bristol & Bath Network).
• dc.format.mimetype application/pdf
• dc.identifier.citation Blackman J, Stankeviciute L, Arenaza-Urquijo EM, Suárez-Calvet M, Sánchez-Benavides G, Vilor-Tejedor N, Iranzo A, Molinuevo JL, Gispert JD, Coulthard E, Grau-Rivera O; European Prevention of Alzheimer’s Disease (EPAD) Consortium. Cross-sectional and longitudinal association of sleep and Alzheimer biomarkers in cognitively unimpaired adults. Brain Commun. 2022 Nov 3;4(6):fcac257. DOI: 10.1093/braincomms/fcac257
• dc.identifier.doi http://dx.doi.org/10.1093/braincomms/fcac257
• dc.identifier.issn 2632-1297
• dc.identifier.uri http://hdl.handle.net/10230/55866
• dc.language.iso eng
• dc.publisher Oxford University Press
• dc.relation.ispartof Brain Commun. 2022 Nov 3;4(6):fcac257
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-111514RA-I00
• dc.rights © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Alzheimer’s disease
• dc.subject.keyword Biomarkers
• dc.subject.keyword Preclinical
• dc.subject.keyword Sleep
• dc.title Cross-sectional and longitudinal association of sleep and Alzheimer biomarkers in cognitively unimpaired adults
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion