Hypothalamic volume, sleep, and APOE genotype in cognitively healthy adults

Introduction: Sleep dysfunction in those at higher risk of dementia may be associated with early structural changes to the hypothalamus. Methods: We used multivariate regression to analyze self-reported sleep (Pittsburgh Sleep Quality Index [PSQI]) from cognitively healthy participants in the PREVEN...

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Autores: Laurell, Axel A. S., Mak, Elijah, Dounavi, Maria-Eleni, Underwood, Benjamin R., Dauvilliers, Yves, Dudas, Robert B., Marguet, Oriane, Ritchie, Craig, Koychev, Ivan, Lawlor, Brian A., Naci, Lorina, Malhotra, Paresh, Grau, Oriol (Grau Rivera), Gispert, Juan Domingo, O'Brien, John T., ALFA Study, PREVENT Dementia Investigators
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:dnet:rdupf_______::23c47135f54e91f941af7d120b57f893
Acesso em linha:https://hdl.handle.net/10230/72879
http://dx.doi.org/10.1002/alz.70244
Access Level:acceso abierto
Palavra-chave:Alzheimer&apos
s disease
Apolipoprotein E
Hypothalamus
Neuroimaging
Sleep
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spelling Hypothalamic volume, sleep, and APOE genotype in cognitively healthy adultsLaurell, Axel A. S.Mak, ElijahDounavi, Maria-EleniUnderwood, Benjamin R.Dauvilliers, YvesDudas, Robert B.Marguet, OrianeRitchie, CraigKoychev, IvanLawlor, Brian A.Naci, LorinaMalhotra, PareshGrau, Oriol (Grau Rivera)Gispert, Juan DomingoO'Brien, John T.ALFA StudyPREVENT Dementia InvestigatorsAlzheimer&aposs diseaseApolipoprotein EHypothalamusNeuroimagingSleepIntroduction: Sleep dysfunction in those at higher risk of dementia may be associated with early structural changes to the hypothalamus. Methods: We used multivariate regression to analyze self-reported sleep (Pittsburgh Sleep Quality Index [PSQI]) from cognitively healthy participants in the PREVENT Dementia and Alzheimer's and Families (ALFA) studies (n = 1939), stratified by apolipoprotein E (APOE) genotype as homozygotes, heterozygotes, and non-carriers. FreeSurfer was used to extract hypothalamic subunit volumes from T1-weighted magnetic resonance images. Results: APOE ε4 homozygotes had a larger anterior-superior hypothalamus compared to heterozygotes and non-carriers, an effect which was driven by younger people in the cohort. APOE ε4 carriers had a higher PSQI global score after age 55, and smaller anterior-superior and tubular-superior subunits were associated with more sleep disturbances. Sleep duration and efficiency worsened with age, but only in participants with a small anterior-inferior hypothalamus. Discussion: This suggests that aging and APOE ε4 are associated with hypothalamic changes, highlighting mechanisms linking sleep dysfunction to dementia. Highlights: Apolipoprotein E (APOE) ε4 homozygotes ha a larger anterior-superior hypothalamus. APOE ε4 carriers have worse sleep, but only after age 55. Worse sleep in APOE ε4 carriers was associated with smaller hypothalamic subunits. Higher age was associated with worse sleep in people with a small hypothalamus.Wiley2026202620252026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/10230/72879http://dx.doi.org/10.1002/alz.70244reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésAlzheimer's and Dementia. 2025 May;21(5):e70244© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:dnet:rdupf_______::23c47135f54e91f941af7d120b57f8932026-06-12T07:21:37Z
dc.title.none.fl_str_mv Hypothalamic volume, sleep, and APOE genotype in cognitively healthy adults
title Hypothalamic volume, sleep, and APOE genotype in cognitively healthy adults
spellingShingle Hypothalamic volume, sleep, and APOE genotype in cognitively healthy adults
Laurell, Axel A. S.
Alzheimer&apos
s disease
Apolipoprotein E
Hypothalamus
Neuroimaging
Sleep
title_short Hypothalamic volume, sleep, and APOE genotype in cognitively healthy adults
title_full Hypothalamic volume, sleep, and APOE genotype in cognitively healthy adults
title_fullStr Hypothalamic volume, sleep, and APOE genotype in cognitively healthy adults
title_full_unstemmed Hypothalamic volume, sleep, and APOE genotype in cognitively healthy adults
title_sort Hypothalamic volume, sleep, and APOE genotype in cognitively healthy adults
dc.creator.none.fl_str_mv Laurell, Axel A. S.
Mak, Elijah
Dounavi, Maria-Eleni
Underwood, Benjamin R.
Dauvilliers, Yves
Dudas, Robert B.
Marguet, Oriane
Ritchie, Craig
Koychev, Ivan
Lawlor, Brian A.
Naci, Lorina
Malhotra, Paresh
Grau, Oriol (Grau Rivera)
Gispert, Juan Domingo
O'Brien, John T.
ALFA Study
PREVENT Dementia Investigators
author Laurell, Axel A. S.
author_facet Laurell, Axel A. S.
Mak, Elijah
Dounavi, Maria-Eleni
Underwood, Benjamin R.
Dauvilliers, Yves
Dudas, Robert B.
Marguet, Oriane
Ritchie, Craig
Koychev, Ivan
Lawlor, Brian A.
Naci, Lorina
Malhotra, Paresh
Grau, Oriol (Grau Rivera)
Gispert, Juan Domingo
O'Brien, John T.
ALFA Study
PREVENT Dementia Investigators
author_role author
author2 Mak, Elijah
Dounavi, Maria-Eleni
Underwood, Benjamin R.
Dauvilliers, Yves
Dudas, Robert B.
Marguet, Oriane
Ritchie, Craig
Koychev, Ivan
Lawlor, Brian A.
Naci, Lorina
Malhotra, Paresh
Grau, Oriol (Grau Rivera)
Gispert, Juan Domingo
O'Brien, John T.
ALFA Study
PREVENT Dementia Investigators
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer&apos
s disease
Apolipoprotein E
Hypothalamus
Neuroimaging
Sleep
topic Alzheimer&apos
s disease
Apolipoprotein E
Hypothalamus
Neuroimaging
Sleep
description Introduction: Sleep dysfunction in those at higher risk of dementia may be associated with early structural changes to the hypothalamus. Methods: We used multivariate regression to analyze self-reported sleep (Pittsburgh Sleep Quality Index [PSQI]) from cognitively healthy participants in the PREVENT Dementia and Alzheimer's and Families (ALFA) studies (n = 1939), stratified by apolipoprotein E (APOE) genotype as homozygotes, heterozygotes, and non-carriers. FreeSurfer was used to extract hypothalamic subunit volumes from T1-weighted magnetic resonance images. Results: APOE ε4 homozygotes had a larger anterior-superior hypothalamus compared to heterozygotes and non-carriers, an effect which was driven by younger people in the cohort. APOE ε4 carriers had a higher PSQI global score after age 55, and smaller anterior-superior and tubular-superior subunits were associated with more sleep disturbances. Sleep duration and efficiency worsened with age, but only in participants with a small anterior-inferior hypothalamus. Discussion: This suggests that aging and APOE ε4 are associated with hypothalamic changes, highlighting mechanisms linking sleep dysfunction to dementia. Highlights: Apolipoprotein E (APOE) ε4 homozygotes ha a larger anterior-superior hypothalamus. APOE ε4 carriers have worse sleep, but only after age 55. Worse sleep in APOE ε4 carriers was associated with smaller hypothalamic subunits. Higher age was associated with worse sleep in people with a small hypothalamus.
publishDate 2025
dc.date.none.fl_str_mv 2025
2026
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/10230/72879
http://dx.doi.org/10.1002/alz.70244
url https://hdl.handle.net/10230/72879
http://dx.doi.org/10.1002/alz.70244
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Alzheimer's and Dementia. 2025 May;21(5):e70244
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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