Laurell Axel A S, Mak Elijah, Dounavi Maria-Eleni, Underwood Benjamin R, Dauvilliers Yves, Dudas Robert B, Marguet Oriane, Ritchie Craig W, Koychev Ivan, Lawlor Brian A, Naci Lorina, Malhotra Paresh, Grau-Rivera Oriol, Gispert Juan Domingo, O'Brien John T
Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Cambridgeshire and Peterborough NHS Foundation Trust, Windsor Research Unit, Fulbourn Hospital, Cambridge, UK.
Alzheimers Dement. 2025 May;21(5):e70244. doi: 10.1002/alz.70244.
Sleep dysfunction in those at higher risk of dementia may be associated with early structural changes to the hypothalamus.
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.
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.
This suggests that aging and APOE ε4 are associated with hypothalamic changes, highlighting mechanisms linking sleep dysfunction to dementia.
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.
痴呆症高危人群的睡眠功能障碍可能与下丘脑早期结构变化有关。
我们使用多变量回归分析了来自预防痴呆症及阿尔茨海默病与家庭（ALFA）研究中认知健康参与者（n = 1939）的自我报告睡眠情况（匹兹堡睡眠质量指数[PSQI]），并根据载脂蛋白E（APOE）基因型分为纯合子、杂合子和非携带者进行分层。使用FreeSurfer从T1加权磁共振图像中提取下丘脑亚单位体积。
与杂合子和非携带者相比，APOE ε4纯合子的下丘脑前上部更大，这一效应在该队列中的年轻人中更为明显。55岁以后，APOE ε4携带者的PSQI全球评分更高，前上部和管状上部亚单位较小与更多的睡眠障碍有关。睡眠时长和效率随年龄增长而恶化，但仅在那些下丘脑前下部较小的参与者中如此。
这表明衰老和APOE ε4与下丘脑变化有关，突出了将睡眠功能障碍与痴呆症联系起来的机制。
载脂蛋白E（APOE）ε4纯合子的下丘脑前上部更大。APOE ε4携带者睡眠较差，但仅在55岁以后。APOE ε4携带者睡眠较差与下丘脑亚单位较小有关。年龄较大与下丘脑较小的人睡眠较差有关。
