Axel A. S. Laurell, Elijah Mak, Maria-Eleni Dounavi, Benjamin R. Underwood, Yves Dauvilliers, Robert B. Dudas, Oriane Marguet, Craig W. Ritchie, Ivan Koychev, Brian A. Lawlor, Lorina Naci, Paresh Malhotra, Oriol Grau-Rivera, Juan Domingo Gispert, John T. O'Brien, for the ALFA study, the PREVENT Dementia Investigators
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O'Brien, for the ALFA study, the PREVENT Dementia Investigators","doi":"10.1002/alz.70244","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> INTRODUCTION</h3>\n \n <p>Sleep dysfunction in those at higher risk of dementia may be associated with early structural changes to the hypothalamus.</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>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 (<i>n</i> = 1939), stratified by apolipoprotein E (<i>APOE</i>) genotype as homozygotes, heterozygotes, and non-carriers. FreeSurfer was used to extract hypothalamic subunit volumes from T1-weighted magnetic resonance images.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p><i>APOE</i> 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. <i>APOE</i> 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.</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>This suggests that aging and <i>APOE</i> ε4 are associated with hypothalamic changes, highlighting mechanisms linking sleep dysfunction to dementia.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>Apolipoprotein E (<i>APOE)</i> ε4 homozygotes ha a larger anterior–superior hypothalamus.</li>\n \n <li><i>APOE</i> ε4 carriers have worse sleep, but only after age 55.</li>\n \n <li>Worse sleep in <i>APOE</i> ε4 carriers was associated with smaller hypothalamic subunits.</li>\n \n <li>Higher age was associated with worse sleep in people with a small hypothalamus.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 5","pages":""},"PeriodicalIF":13.0000,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70244","citationCount":"0","resultStr":"{\"title\":\"Hypothalamic volume, sleep, and APOE genotype in cognitively healthy adults\",\"authors\":\"Axel A. 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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 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.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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