Hand Lauren K, Key Mickeal N, Vidoni Eric D, Ludwig Rebecca, Nelson Eryen, Glaser Allison, Drerup Michelle, Phadnis Milind A, Bruce Jared, Burns Jeffrey M, Siengsukon Catherine F
Department of Physical Therapy, Rehabilitation Science, and Athletic Training, University of Kansas Medical Center, Kansas City, Kansas, USA.
University of Kansas Alzheimer's Disease Research Center, Fairway, Kansas, USA.
J Sleep Res. 2025 Jun 3:e70098. doi: 10.1111/jsr.70098.
Insomnia increases the risk of Alzheimer's disease and is associated with increased amyloid-β (Aβ) levels, but assessments using rigorous objective measures are lacking. The purpose of this cross-sectional study was to determine the association between sleep characteristics and Aβ burden using polysomnography and positron emission tomography (PET). Cognitively normal older adults (ages 60-85) with symptoms of insomnia underwent PET and overnight polysomnography. Pearson correlations determined the association between sleep variables and the standard uptake values ratio (SUVR) within global cerebral cortex, precuneus, posterior cingulate cortex (PCC), and the medial prefrontal cortex (mPFC). Multivariable stepwise regression was performed for each region of interest with apolipoprotein-ε (APOE) genotype and age as potential covariates. Sleep parameters between those who were Aβ elevated vs. non-elevated were compared using t-tests. Forty-three adults (69.3 ± 5.5 years old; 32.6% Aβ elevated; mostly non-Hispanic white and female) were included in analyses. Longer stage 1 was related to greater cortical and mPFC SUVR, greater wake after sleep onset was related to greater cortical, mPFC, and precuneus SUVR, and shorter stage 2 was associated with greater PCC SUVR. Compared to those who were Aβ non-elevated, those who were Aβ elevated had longer stage 1 and shorter stage 2 sleep. Greater sleep fragmentation, longer stage 1 sleep, and shorter stage 2 sleep were associated with greater Aβ burden in various regions of the brain in cognitively normal older adults. The results support poor sleep as an early risk factor for Aβ accumulation and possible target for Alzheimer's prevention. Trial Registration: The study was registered on clinicaltrials.gov (NCT03954210).
失眠会增加患阿尔茨海默病的风险，且与淀粉样蛋白β（Aβ）水平升高有关，但缺乏使用严格客观测量方法的评估。这项横断面研究的目的是利用多导睡眠图和正电子发射断层扫描（PET）来确定睡眠特征与Aβ负荷之间的关联。有失眠症状的认知正常的老年人（60 - 85岁）接受了PET和夜间多导睡眠图检查。Pearson相关性分析确定了睡眠变量与全脑皮质、楔前叶、后扣带回皮质（PCC）和内侧前额叶皮质（mPFC）内的标准摄取值比率（SUVR）之间的关联。对每个感兴趣区域进行多变量逐步回归分析，将载脂蛋白ε（APOE）基因型和年龄作为潜在协变量。使用t检验比较Aβ升高组与未升高组之间的睡眠参数。43名成年人（69.3±5.5岁；32.6%的人Aβ升高；大多数为非西班牙裔白人且为女性）纳入分析。第1期睡眠时间越长，皮质和mPFC的SUVR越高；睡眠开始后觉醒时间越长，皮质、mPFC和楔前叶的SUVR越高；第2期睡眠时间越短，PCC的SUVR越高。与Aβ未升高者相比，Aβ升高者第1期睡眠时间更长，第2期睡眠时间更短。在认知正常的老年人中，更大的睡眠碎片化、更长的第1期睡眠时间和更短的第2期睡眠时间与大脑各区域更大的Aβ负荷相关。这些结果支持睡眠质量差是Aβ积累的早期危险因素以及阿尔茨海默病预防的可能靶点。试验注册：该研究已在clinicaltrials.gov上注册（NCT03954210）。
