Mullins Anna E, Parekh Ankit, Kam Korey, Castillo Bresne, Roberts Zachary J, Fakhoury Ahmad, Valencia Daphne I, Schoenholz Reagan, Tolbert Thomas M, Bronstein Jason Z, Mooney Anne M, Burschtin Omar E, Rapoport David M, Ayappa Indu, Varga Andrew W
Division of Pulmonary, Critical Care, and Sleep Medicine, Mount Sinai Integrative Sleep Center, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Front Physiol. 2021 Nov 22;12:750516. doi: 10.3389/fphys.2021.750516. eCollection 2021.
Obstructive sleep apnea (OSA) is considered to impair memory processing and increase the expression of amyloid-β (Aβ) and risk for Alzheimer's disease (AD). Given the evidence that slow-wave sleep (SWS) is important in both memory and Aβ metabolism, a better understanding of the mechanisms by which OSA impacts memory and risk for AD can stem from evaluating the role of disruption of SWS specifically and, when such disruption occurs through OSA, from evaluating the individual contributions of sleep fragmentation (SF) and intermittent hypoxemia (IH). In this study, we used continuous positive airway pressure (CPAP) withdrawal to recapitulate SWS-specific OSA during polysomnography (PSG), creating conditions of both SF and IH in SWS only. During separate PSGs, we created the conditions of SWS fragmentation but used oxygen to attenuate IH. We studied 24 patients (average age of 55 years, 29% female) with moderate-to-severe OSA [Apnea-Hypopnea Index (AHI); AHI4% > 20/h], who were treated and adherent to CPAP. Participants spent three separate nights in the laboratory under three conditions as follows: (1) consolidated sleep with CPAP held at therapeutic pressure (); (2) CPAP withdrawn exclusively in SWS ( ) breathing room air; and (3) CPAP withdrawn exclusively in SWS with the addition of oxygen during pressure withdrawal ( + ). Multiple measures of SF (e.g., arousal index) and IH (e.g., hypoxic burden), during SWS, were compared according to condition. Arousal index in SWS during CPAP withdrawal was significantly greater compared to CPAP but not significantly different with and without oxygen ( = 1.1/h, + = 10.7/h, = 10.6/h). However, hypoxic burden during SWS was significantly reduced with oxygen compared to without oxygen [ + = 23 (%min)/h, = 37 (%min)/h]. No significant OSA was observed in non-rapid eye movement (REM) stage 1 (NREM 1), non-REM stage 2 (NREM 2), or REM sleep (e.g., non-SWS) in any condition. The SWS-specific CPAP withdrawal induces OSA with SF and IH. The addition of oxygen during CPAP withdrawal results in SF with significantly less severe hypoxemia during the induced respiratory events in SWS. This model of SWS-specific CPAP withdrawal disrupts SWS with a physiologically relevant stimulus and facilitates the differentiation of SF and IH in OSA.
阻塞性睡眠呼吸暂停（OSA）被认为会损害记忆处理，并增加β-淀粉样蛋白（Aβ）的表达以及患阿尔茨海默病（AD）的风险。鉴于有证据表明慢波睡眠（SWS）在记忆和Aβ代谢中都很重要，要更好地理解OSA影响记忆和AD风险的机制，可以通过专门评估SWS中断的作用来实现；当这种中断通过OSA发生时，则可以通过评估睡眠片段化（SF）和间歇性低氧血症（IH）的个体作用来实现。在本研究中，我们采用持续气道正压通气（CPAP）撤机的方法，在多导睡眠图（PSG）期间重现特定于SWS的OSA，仅在SWS中创造SF和IH的条件。在单独的PSG期间，我们创造了SWS片段化的条件，但使用氧气来减轻IH。我们研究了24例中度至重度OSA [呼吸暂停低通气指数（AHI）；AHI4%>20次/小时]的患者（平均年龄55岁，29%为女性），这些患者接受了CPAP治疗且依从性良好。参与者在实验室里在三种条件下分别度过三个夜晚，具体如下：（1）在治疗压力下持续使用CPAP进行巩固睡眠（ ）；（2）仅在SWS期间撤掉CPAP（ ）并呼吸室内空气；（3）仅在SWS期间撤掉CPAP，并在撤机期间补充氧气（ + ）。根据条件比较了SWS期间SF（如觉醒指数）和IH（如低氧负荷）的多种测量指标。撤掉CPAP期间SWS的觉醒指数与使用CPAP时相比显著更高，但在补充氧气和未补充氧气的情况下无显著差异（ = 1.1次/小时， + = 10.7次/小时， = 10.6次/小时）。然而，与未补充氧气相比，补充氧气时SWS期间的低氧负荷显著降低[ + = 23（%分钟）/小时， = 37（%分钟）/小时]。在任何条件下，非快速眼动（REM）睡眠1期（NREM 1）、非REM睡眠2期（NREM 2）或REM睡眠（如非SWS）中均未观察到明显的OSA。特定于SWS的CPAP撤机可诱导伴有SF和IH的OSA。CPAP撤机期间补充氧气会导致SF，且在SWS中诱发的呼吸事件期间低氧血症的严重程度显著降低。这种特定于SWS的CPAP撤机模型通过生理相关刺激破坏SWS，并有助于区分OSA中的SF和IH。
