{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:50:57Z","timestamp":1791283857297,"version":"4.1.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":266,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015442","name":"Global Brain Health Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015442","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer\u2019s Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["PI25\/00222"],"award-info":[{"award-number":["PI25\/00222"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003030","name":"Ag\u00e8ncia de Gesti\u00f3 d'Ajuts Universitaris i de Recerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015439","name":"Research Centres of Catalonia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015439","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Joan Rod\u00e9s\u2014Josep Baselga Research"},{"DOI":"10.13039\/501100005142","name":"Banco Bilbao Vizcaya Argentaria (BBVA) Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005142","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sleep disturbances are frequently observed in patients with neurodegenerative diseases, but in vivo evidence linking subcortical sleep\u2013wake structures to sleep phenotypes is limited. We aim to examine associations between MRI-derived measures of subcortical sleep\u2013wake regulating regions and polysomnographic sleep parameters in individuals with Alzheimer\u2019s disease and cognitively healthy controls. Fifty-seven adults (45 with biomarker-confirmed Alzheimer\u2019s disease and 12 cognitively healthy controls with normal pTau217 plasma levels) were recruited at the Hospital Cl\u00ednic de Barcelona. All participants completed overnight polysomnography and 3T brain MRI, including a neuromelanin-sensitive sequence. MRI-derived measures of wake-promoting structures [locus coeruleus (LC), posterior hypothalamus and basal forebrain] and sleep-promoting regions (anterior hypothalamus) were obtained. We estimated the association between nocturnal polysomnographic variables [including total sleep time, sleep efficiency, time in rapid eye movement (REM) and non-REM sleep stages, REM sleep latency, wake after sleep onset and arousals] and MRI-derived measures. Then, a principal component analysis (PCA) was used to obtain derived patterns of sleep\u2013wake regulation. Among sleep-promoting regions, higher anterior hypothalamic volumes correlated with greater time in bed (\u03c1 = 0.19, P &amp;lt; 0.05), increased sleep period time (SPT) (\u03c1 = 0.25, P &amp;lt; 0.01), and decreased REM over SPT (\u03c1 = \u22120.22, P &amp;lt; 0.05). Within wake-promoting structures, higher posterior hypothalamic volume and LC integrity were associated with higher arousals (\u03c1 = 0.32, P &amp;lt; 0.05 and \u03c1 = 0.18, P &amp;lt; 0.05, respectively), and higher basal forebrain volume was associated with less REM over SPT (\u03c1 = \u22120.25, P &amp;lt; 0.05). Control anatomic regions showed no associations with sleep parameters. The first two principal components of the PCA explain 47.7% of the variance. Anterior hypothalamic volumes clustered with longer, more efficient sleep, whereas LC integrity aligned with increased wakefulness and REM sleep latency. Alzheimer\u2019s disease participants showed a shift towards the latter pattern, indicating disrupted sleep\u2013wake regulation. MRI-derived measures of subcortical sleep\u2013wake regions were associated with clinical sleep phenotypes in Alzheimer\u2019s disease and ageing. These in vivo findings align with prior post-mortem research, reinforcing the role of subcortical structures in sleep disturbances and highlighting these circuits as potential targets to alleviate sleep symptoms and modify disease progression.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag360","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:58:15Z","timestamp":1790164695000},"source":"Crossref","is-referenced-by-count":0,"title":["Subcortical correlates of sleep in aging and Alzheimer\u2019s disease: an\n                    <i>in vivo<\/i>\n                    study"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3006-9792","authenticated-orcid":false,"given":"Agn\u00e8s","family":"P\u00e9rez-Millan","sequence":"first","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Hospital Cl\u00ednic de Barcelona, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona-IDIBAPS , Barcelona CP08036, Catalonia ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED) , Madrid CP28029 ,","place":["Spain"]},{"name":"eHealth Center, Faculty of Computer Science, Multimedia and Telecommunications, Universitat Oberta de Catalunya , Barcelona CP08018 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"May\u00e0","sequence":"additional","affiliation":[{"name":"Sleep Unit, Neurology Service, Hospital Cl\u00ednic Universitari de Barcelona, University of Barcelona , Barcelona CP08036 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Mart\u00edn-Sobrino","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Hospital Cl\u00ednic de Barcelona, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona-IDIBAPS , Barcelona CP08036, Catalonia ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Pe\u00f1a-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Magnetic Resonance Imaging Core Facility, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) , Barcelona CP08036, Catalonia ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Val-Guardiola","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Hospital Cl\u00ednic de Barcelona, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona-IDIBAPS , Barcelona CP08036, Catalonia ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guadalupe","family":"Fern\u00e1ndez-Villullas","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Hospital Cl\u00ednic de Barcelona, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona-IDIBAPS , Barcelona CP08036, Catalonia ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED) , Madrid CP28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Bosch","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Hospital Cl\u00ednic de Barcelona, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona-IDIBAPS , Barcelona CP08036, Catalonia ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED) , Madrid CP28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adri\u00e0","family":"Tort-Merino","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Hospital Cl\u00ednic de Barcelona, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona-IDIBAPS , Barcelona CP08036, Catalonia ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED) , Madrid CP28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Llad\u00f3","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Hospital Cl\u00ednic de Barcelona, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona-IDIBAPS , Barcelona CP08036, Catalonia ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED) , Madrid CP28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Morales-Ruiz","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Department-CDB, Hospital Clinic, IDIBAPS, CIBERehd , Barcelona CP08036 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M","family":"Walsh","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fein Memory and Aging Center, Weill Institute for Neurosciences, University of California , San Francisco, CA 94143 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1572-2626","authenticated-orcid":false,"given":"Thomas C","family":"Neylan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fein Memory and Aging Center, Weill Institute for Neurosciences, University of California , San Francisco, CA 94143 ,","place":["USA"]},{"name":"Department of Psychiatry, University of California , San Francisco, CA 94143 ,","place":["USA"]},{"name":"San Francisco Veterinary Affairs Medical Center , San Francisco, CA 94121 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carles","family":"Gaig","sequence":"additional","affiliation":[{"name":"Sleep Unit, Neurology Service, Hospital Cl\u00ednic Universitari de Barcelona, University of Barcelona , Barcelona CP08036 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Mu\u00f1oz-Moreno","sequence":"additional","affiliation":[{"name":"Magnetic Resonance Imaging Core Facility, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) , Barcelona CP08036, Catalonia ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7750-896X","authenticated-orcid":false,"given":"Raquel","family":"S\u00e1nchez-Valle","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Hospital Cl\u00ednic de Barcelona, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona-IDIBAPS , Barcelona CP08036, Catalonia ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED) , Madrid CP28029 ,","place":["Spain"]},{"name":"Universitat de Barcelona , Barcelona CP08036 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Iranzo","sequence":"additional","affiliation":[{"name":"Sleep Unit, Neurology Service, Hospital Cl\u00ednic Universitari de Barcelona, University of Barcelona , Barcelona CP08036 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea T","family":"Grinberg","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic , Jacksonville, FL 32224 ,","place":["USA"]},{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic , Jacksonville, FL 32224 ,","place":["USA"]},{"name":"Department of Pathology, University of Sao Paulo Medical School , Sao Paulo 01246-903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neus","family":"Falg\u00e0s","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Hospital Cl\u00ednic de Barcelona, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona-IDIBAPS , Barcelona CP08036, Catalonia ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Neurodegenerativas (CIBERNED) , Madrid CP28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"issue":"10","key":"2026100605563369600_fcag360-B1","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/S1474-4422(14)70172-3","article-title":"Connections between sleep and cognition in older adults","volume":"13","author":"Yaffe","year":"2014","journal-title":"Lancet 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