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快速眼动睡眠、神经退行性变与衰老过程中的淀粉样蛋白沉积

Rapid Eye Movement Sleep, Neurodegeneration, and Amyloid Deposition in Aging.

作者信息

André Claire, Champetier Pierre, Rehel Stéphane, Kuhn Elizabeth, Touron Edelweiss, Ourry Valentin, Landeau Brigitte, Le Du Gwendoline, Mézenge Florence, Segobin Shailendra, de la Sayette Vincent, Vivien Denis, Chételat Gaël, Rauchs Géraldine

机构信息

Normandie Univ, UNICAEN, INSERM, U1237, PhIND "Physiopathology and Imaging of Neurological Disorders", NeuroPresage Team, GIP Cyceron, Caen, France.

Normandie Univ, UNICAEN, PSL Université, EPHE, INSERM, U1077, Caen University Hospital, GIP Cyceron, NIMH, Caen, France.

出版信息

Ann Neurol. 2023 May;93(5):979-990. doi: 10.1002/ana.26604. Epub 2023 Jan 27.

Abstract

OBJECTIVE

Rapid eye movement (REM) sleep is markedly altered in Alzheimer's disease (AD), and its reduction in older populations is associated with AD risk. However, little is known about the underlying brain mechanisms. Our objective was to investigate the relationships between REM sleep integrity and amyloid deposition, gray matter volume, and perfusion in aging.

METHODS

We included 121 cognitively unimpaired older adults (76 women, mean age 68.96 ± 3.82 years), who underwent a polysomnography, T1-weighted magnetic resonance imaging, early and late Florbetapir positron emission tomography scans to evaluate gray matter volume, perfusion, and amyloid deposition. We computed indices reflecting REM sleep macro- and microstructural integrity (ie, normalized electroencephalographic spectral power values). Voxel-wise multiple regression analyses were conducted between REM sleep indices and neuroimaging data, controlling for age, sex, education, the apnea-hypopnea index, and the apolipoprotein E ε4 status.

RESULTS

Lower perfusion in frontal, anterior and posterior cingulate, and precuneus areas was associated with decreased delta power and electroencephalographic slowing (slow/fast frequencies ratio), and increased alpha and beta power. To a lower extent, similar results were obtained between gray matter volume and delta, alpha, and beta power. In addition, lower REM sleep theta power was more marginally associated with greater diffuse amyloid deposition and lower gray matter volume in fronto-temporal and parieto-occipital areas.

INTERPRETATION

These results suggest that alterations of REM sleep microstructure are associated with greater neurodegeneration and neocortical amyloid deposition in older adults. Further studies are warranted to replicate these findings, and determine whether older adults exhibiting REM sleep alterations are more at risk of cognitive decline and belonging to the Alzheimer's continuum. ANN NEUROL 2023;93:979-990.

摘要

目的

快速眼动(REM)睡眠在阿尔茨海默病(AD)中显著改变,在老年人群中其减少与AD风险相关。然而,其潜在的脑机制尚不清楚。我们的目的是研究衰老过程中REM睡眠完整性与淀粉样蛋白沉积、灰质体积和灌注之间的关系。

方法

我们纳入了121名认知未受损的老年人(76名女性,平均年龄68.96±3.82岁),他们接受了多导睡眠图检查、T1加权磁共振成像、早期和晚期氟代硼替佐米正电子发射断层扫描,以评估灰质体积、灌注和淀粉样蛋白沉积。我们计算了反映REM睡眠宏观和微观结构完整性的指标(即标准化脑电图频谱功率值)。在控制年龄、性别、教育程度、呼吸暂停低通气指数和载脂蛋白Eε4状态的情况下,对REM睡眠指标与神经影像学数据进行了体素级多元回归分析。

结果

额叶、前扣带回和后扣带回以及楔前叶区域灌注降低与δ功率降低和脑电图减慢(慢/快频率比)以及α和β功率增加有关。在灰质体积与δ、α和β功率之间也获得了类似但程度较低的结果。此外,较低的REM睡眠θ功率与额颞叶和顶枕叶区域更大的弥漫性淀粉样蛋白沉积和更低的灰质体积之间存在更微弱的关联。

解读

这些结果表明,老年人REM睡眠微观结构的改变与更大程度的神经退行性变和新皮质淀粉样蛋白沉积有关。有必要进一步研究以重复这些发现,并确定表现出REM睡眠改变的老年人是否更易出现认知衰退以及是否属于阿尔茨海默病连续体。《神经病学年鉴》2023;93:979 - 990。

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