{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:34:26Z","timestamp":1790879666446,"version":"4.1.0"},"reference-count":72,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000320","name":"Alzheimer's Society","doi-asserted-by":"publisher","award":["178"],"award-info":[{"award-number":["178"]}],"id":[{"id":"10.13039\/501100000320","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000320","name":"Alzheimer's Society","doi-asserted-by":"publisher","award":["264"],"award-info":[{"award-number":["264"]}],"id":[{"id":"10.13039\/501100000320","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000320","name":"Alzheimer's Society","doi-asserted-by":"publisher","award":["329"],"award-info":[{"award-number":["329"]}],"id":[{"id":"10.13039\/501100000320","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["TriBEKa\u201017\u2010519007"],"award-info":[{"award-number":["TriBEKa\u201017\u2010519007"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018956","name":"NIHR Cambridge Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR203312"],"award-info":[{"award-number":["NIHR203312"]}],"id":[{"id":"10.13039\/501100018956","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/00117"],"award-info":[{"award-number":["PI19\/00117"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI24\/00116"],"award-info":[{"award-number":["PI24\/00116"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Sleep dysfunction in those at higher risk of dementia may be associated with early structural changes to the hypothalamus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We used multivariate regression to analyze self\u2010reported sleep (Pittsburgh Sleep Quality Index [PSQI]) from cognitively healthy participants in the PREVENT Dementia and Alzheimer's and Families (ALFA) studies (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a01939), stratified by apolipoprotein E (\n                      <jats:italic>APOE<\/jats:italic>\n                      ) genotype as homozygotes, heterozygotes, and non\u2010carriers. FreeSurfer was used to extract hypothalamic subunit volumes from T1\u2010weighted magnetic resonance images.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 homozygotes had a larger anterior\u2013superior hypothalamus compared to heterozygotes and non\u2010carriers, an effect which was driven by younger people in the cohort.\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 carriers had a higher PSQI global score after age 55, and smaller anterior\u2013superior and tubular\u2013superior subunits were associated with more sleep disturbances. Sleep duration and efficiency worsened with age, but only in participants with a small anterior\u2013inferior hypothalamus.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      This suggests that aging and\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 are associated with hypothalamic changes, highlighting mechanisms linking sleep dysfunction to dementia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            Apolipoprotein E (\n                            <jats:italic>APOE)<\/jats:italic>\n                            \u03b54 homozygotes ha a larger anterior\u2013superior hypothalamus.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:italic>APOE<\/jats:italic>\n                            \u03b54 carriers have worse sleep, but only after age 55.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Worse sleep in\n                            <jats:italic>APOE<\/jats:italic>\n                            \u03b54 carriers was associated with smaller hypothalamic subunits.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Higher age was associated with worse sleep in people with a small hypothalamus.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70244","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T08:30:52Z","timestamp":1748334652000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Hypothalamic volume, sleep, and\n                    <i>APOE<\/i>\n                    genotype in cognitively healthy adults"],"prefix":"10.1002","volume":"21","author":[{"given":"Axel A. S.","family":"Laurell","sequence":"first","affiliation":[{"name":"Department of Psychiatry University of Cambridge, Addenbrooke's Hospital  Cambridge UK"},{"name":"Cambridgeshire and Peterborough NHS Foundation Trust, Windsor Research Unit Fulbourn Hospital  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elijah","family":"Mak","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Cambridge, Addenbrooke's Hospital  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria\u2010Eleni","family":"Dounavi","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Cambridge, Addenbrooke's Hospital  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin R.","family":"Underwood","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Cambridge, Addenbrooke's Hospital  Cambridge UK"},{"name":"Cambridgeshire and Peterborough NHS Foundation Trust, Windsor Research Unit Fulbourn Hospital  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Dauvilliers","sequence":"additional","affiliation":[{"name":"Sleep\u2010Wake Disorders Center Department of Neurology Gui\u2010de\u2010Chauliac Hospital, CHU Montpellier Universit\u00e9 de Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"Dudas","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Cambridge, Addenbrooke's Hospital  Cambridge UK"},{"name":"Cambridgeshire and Peterborough NHS Foundation Trust, Windsor Research Unit Fulbourn Hospital  Cambridge UK"},{"name":"Department of Psychiatry University of East Anglia  Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriane","family":"Marguet","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig W.","family":"Ritchie","sequence":"additional","affiliation":[{"name":"School of Medicine University of St Andrews  St Andrews UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Koychev","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Oxford Warneford Hospital  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian A.","family":"Lawlor","sequence":"additional","affiliation":[{"name":"Global Brain Health Institute, Trinity College Dublin  Dublin UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorina","family":"Naci","sequence":"additional","affiliation":[{"name":"Trinity College Institute of Neuroscience, Trinity College Dublin  Dublin UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paresh","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences Imperial College London, Burlington Danes, The Hammersmith Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriol","family":"Grau\u2010Rivera","sequence":"additional","affiliation":[{"name":"Barcelona\u03b2eta Brain Research Center, Pasqual Maragall Foundation  Barcelona Spain"},{"name":"Universitat Pompeu Fabra (UPF)  Barcelona Spain"},{"name":"Hospital del Mar Medical Research Institute  Barcelona Spain"},{"name":"Servei de Neurologia Hospital del Mar  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBER\u2010FES), Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Domingo","family":"Gispert","sequence":"additional","affiliation":[{"name":"Barcelona\u03b2eta Brain Research Center, Pasqual Maragall Foundation  Barcelona Spain"},{"name":"Universitat Pompeu Fabra (UPF)  Barcelona Spain"},{"name":"Hospital del Mar Medical Research Institute  Barcelona Spain"},{"name":"Servei de Neurologia Hospital del Mar  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBER\u2010FES), Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Cambridge, Addenbrooke's Hospital  Cambridge UK"},{"name":"Cambridgeshire and Peterborough NHS Foundation Trust, Windsor Research Unit Fulbourn Hospital  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the ALFA study","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the PREVENT Dementia Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12521"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2024.1755"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004171"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.13573"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101782"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn944"},{"key":"e_1_2_9_8_1","doi-asserted-by":"crossref","unstructured":"LaurellAAS ShahSN RahmatiM O'BrienJT UnderwoodBR.Hypothalamic structure and function in Alzheimer's disease and Lewy\u2010body dementia: a systematic review and meta\u2010analysis2024:2024.09.03.24312999 [Preprint]. doi:10.1101\/2024.09.03.24312999","DOI":"10.1101\/2024.09.03.24312999"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-017-8613-x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2011.52"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010024\u201002931\u2010w"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.22.2888"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000134671.99649.32"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/32.11.1507"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300060515611539"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102350\u20102\u20109"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.10.002"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD\u2010223511"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsae094"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003255"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0191281"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010020\u201000740\u20100"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen\u20102012\u2010001893"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3109\/09540261.2013.869195"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcae189"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2016.02.003"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165\u20101781(89)90047\u20104"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2015.00166"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/frsle.2023.1226824"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1177\/014662167700100306"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100447.1983.tb09716.x"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2020.117287"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.121.262464"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2023.103478"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.664781"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010020\u20100879\u20103"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006082"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102020\u2010322924"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678x211020863"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678x231173587"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2020.03.006"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2020.10.029"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcae046"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcad351"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.26798"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu222"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102017\u2010315795"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.07.013"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1558\u20105646.1957.tb02911.x"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.02.008"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhl103"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201066114\u20106"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0102477"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201041078\u20105"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111200"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2018.3597"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201079289\u20109"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201053578\u20104"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59660"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004\u20101520"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0063136"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2017.01.011"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.2510"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.01.007"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2014.00119"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1159\/000514967"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.13\u201003\u201001065.1993"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2019.04.001"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/11.6.490"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304\u20103940(96)12787\u20107"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1999.7185"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/27.7.1255"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70244","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.70244","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70244","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:29:57Z","timestamp":1789558197000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.70244"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":72,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1002\/alz.70244"],"URL":"https:\/\/doi.org\/10.1002\/alz.70244","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5]]},"assertion":[{"value":"2024-11-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70244"}}