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阻塞性睡眠呼吸暂停与早期但可能可改变的阿尔茨海默病生物标志物变化相关。

Obstructive Sleep Apnea is Associated With Early but Possibly Modifiable Alzheimer's Disease Biomarkers Changes.

作者信息

Liguori Claudio, Mercuri Nicola Biagio, Izzi Francesca, Romigi Andrea, Cordella Alberto, Sancesario Giuseppe, Placidi Fabio

机构信息

Sleep Medicine Centre, Neurophysiopathology Unit, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.

Fondazione Santa Lucia IRCCS, Rome, Italy.

出版信息

Sleep. 2017 May 1;40(5). doi: 10.1093/sleep/zsx011.

Abstract

STUDY OBJECTIVES

Obstructive sleep apnea (OSA) is a common sleep disorder. The, literature lacks studies examining sleep, cognition, and Alzheimer's Disease (AD) cerebrospinal fluid (CSF) biomarkers in OSA patients. Therefore, we first studied cognitive performances, polysomnographic sleep, and CSF β-amyloid42, tau proteins, and lactate levels in patients affected by subjective cognitive impairment (SCI) divided in three groups: OSA patients (showing an Apnea-Hypopnea Index [AHI] ≥15/hr), controls (showing an AHI < 15/hr), and patients with OSA treated by continuous positive airway pressure (CPAP).

METHODS

We compared results among 25 OSA, 10 OSA-CPAP, and 15 controls who underwent a protocol counting neuropsychological testing in the morning, 48-hr polysomnography followed by CSF analysis.

RESULTS

OSA patients showed lower CSF Aβ42 concentrations, higher CSF lactate levels, and higher t-tau/Aβ42 ratio compared to controls and OSA-CPAP patients. OSA patients also showed reduced sleep quality and continuity and lower performances at memory, intelligence, and executive tests than controls and OSA-CPAP patients. We found significant relationships among higher CSF tau proteins levels, sleep impairment, and increased CSF lactate levels in the OSA group. Moreover, lower CSF Aβ42 levels correlate with memory impairment and nocturnal oxygen saturation parameters in OSA patients.

CONCLUSIONS

We hypothesize that OSA reducing sleep quality and producing intermittent hypoxia lowers CSF Aβ42 levels, increases CSF lactate levels, and alters cognitive performances in SCI patients, thus inducing early AD clinical and neuropathological biomarkers changes. Notably, controls as well as OSA-CPAP SCI patients did not show clinical and biochemical AD markers. Therefore, OSA may induce early but possibly CPAP-modifiable AD biomarkers changes.

摘要

研究目的

阻塞性睡眠呼吸暂停(OSA)是一种常见的睡眠障碍。文献中缺乏对OSA患者的睡眠、认知及阿尔茨海默病(AD)脑脊液(CSF)生物标志物的研究。因此,我们首先研究了主观认知障碍(SCI)患者的认知表现、多导睡眠图睡眠情况以及CSFβ-淀粉样蛋白42、tau蛋白和乳酸水平,这些患者被分为三组:OSA患者(呼吸暂停低通气指数[AHI]≥15次/小时)、对照组(AHI<15次/小时)以及接受持续气道正压通气(CPAP)治疗的OSA患者。

方法

我们比较了25例OSA患者、10例OSA-CPAP患者和15例对照组的结果,这些患者接受了一项方案,包括早晨的神经心理学测试、48小时多导睡眠图检查,随后进行CSF分析。

结果

与对照组和OSA-CPAP患者相比,OSA患者的CSF Aβ42浓度较低,CSF乳酸水平较高,t-tau/Aβ42比值较高。与对照组和OSA-CPAP患者相比,OSA患者的睡眠质量和连续性也较差,在记忆、智力和执行测试中的表现较低。我们发现OSA组中较高的CSF tau蛋白水平、睡眠障碍和升高的CSF乳酸水平之间存在显著关系。此外,较低的CSF Aβ42水平与OSA患者的记忆障碍和夜间血氧饱和度参数相关。

结论

我们推测,OSA降低睡眠质量并产生间歇性缺氧,会降低SCI患者的CSF Aβ42水平,升高CSF乳酸水平,并改变认知表现,从而导致早期AD临床和神经病理学生物标志物发生变化。值得注意的是,对照组以及OSA-CPAP SCI患者未显示出临床和生化AD标志物。因此,OSA可能会诱导早期但可能可通过CPAP改善的AD生物标志物变化。

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