Mild Cognitive Impairment and Obstructive Sleep Apnea

描述（由申请人提供）：轻度认知障碍（MCI）是介于正常衰老和阿尔茨海默病（AD）之间的过渡阶段，以记忆障碍为特征，但日常功能很少或没有下降。每年高达15%的轻度认知损伤老年人（oaMCI）转化为AD。很少有干预措施能有效延缓oaMCI患者的认知能力下降和维持日常功能。然而，对合并症阻塞性睡眠呼吸暂停（OSA）的治疗可能有延缓认知能力下降的潜力。大约60%患有轻度认知障碍和早期AD的老年人患有OSA，而在一般人群中只有7-18%的老年人患有OSA。阻塞性睡眠呼吸暂停的特征是夜间发作性上气道塌陷并伴有呼吸减少和/或停止，可导致缺氧、睡眠片段化、白天嗜睡和认知功能障碍。持续气道正压通气（CPAP）是一种睡眠时佩戴的加压鼻罩，可以有效治疗阻塞性睡眠呼吸暂停，但关于其在这一人群中的疗效的信息很少。没有人回答是否使用CPAP治疗oaMCI的OSA延迟认知能力下降并保留日常功能的问题。在Aim 1中，我们将进行一项为期6个月的随机对照临床试验，以评估在患有遗忘性轻度认知障碍和OSA的老年人中，与假性CPAP （n=35）相比，活动性CPAP （n=75）对认知和日常功能的影响大小。然后，我们建议在一项开放标签试验中对活性CPAP组再进行6个月的随访，以估计CPAP治疗依从性对认知和日常功能的影响大小。CPAP依从性可以通过一个隐藏的传感器精确测量，该传感器可以确定在规定压力下使用的小时数。在Aim 2中，我们将探讨CPAP治疗依从性、控制基线OSA严重程度、既往脑血管疾病和缺氧缺血性脑损伤的神经影像学证据、ApoE4以及先前确定的人口统计学和其他患者因素是否能预测1年后活动性CPAP治疗后的认知和日常功能。目标3将确定我们的参与者招募和保留计划以及其他研究方法的可行性，以便为全面试验提供信息。目的4将通过将神经影像学生物标志物[海马体积（原发性）、区域脑体积和厚度、海马亚区体积、缺血性病变体积和脑血流量]与1年临床变化相关联，探讨神经影像学在量化CPAP对大脑影响方面的有效性。这些结果将为全面试验的神经影像学结果测量提供信息。本研究的主要目标是确定一项全面试验的效应大小、研究设计和方法的可行性，该试验将确定oaMCI患者的OSA治疗是否会延缓认知能力下降并保持日常功能。其他潜在的研究好处是增加了对oaMCI和OSA认知能力下降的生理机制的理解，以及最有可能从这种治疗中受益的患者的特征。

DESCRIPTION (provided by applicant): Mild cognitive impairment (MCI), characterized by memory impairment but little or no decline in everyday function, is a transitional stage between normal aging and Alzheimer's Disease (AD). Up to 15% of older adults with MCI (oaMCI) convert to AD annually. Few interventions effectively delay cognitive decline and preserve everyday function in oaMCI. However, treatment of comorbid obstructive sleep apnea (OSA) may have potential for delaying cognitive decline. Approximately 60% of older adults with MCI and early AD have OSA, compared to only 7-18% of older adults in the general population.OSA, which is characterized by episodic nocturnal collapse of the upper airway in conjunction with reduction and/or cessation of breathing, causes hypoxia, fragmented sleep, daytime sleepiness, and cognitive dysfunction. OSA is effectively treated with continuous positive airway pressure (CPAP), a pressurized nasal mask worn during sleep, but there is little information on its efficacy in this population. No one has answered the question of whether treatment of OSA in oaMCI with CPAP delays cognitive decline and preserves everyday function. In Aim 1 we will conduct a 6-month randomized controlled pilot clinical trial to estimate the effect size associated with active CPAP (n=75) compared to sham CPAP (n=35) on cognitive and everyday function in older adults with amnestic mild cognitive impairment and OSA. We then propose to follow the active CPAP group for 6 additional months in an open-label trial to estimate the effect size associated with CPAP treatment adherence on cognitive and everyday function. CPAP adherence can be measured precisely with a hidden sensor that determines hours of use at prescribed pressure. In Aim 2 we will explore whether CPAP treatment adherence, controlling for OSA severity at baseline, neuroimaging evidence of pre-existing cerebrovascular disease and hypoxic ischemic brain injury, ApoE4, and previously identified demographic and other patient factors, predicts cognitive and everyday function after 1 year of active CPAP. Aim 3 will determine the feasibility of our participant recruitment and retention plans and other study methods to inform a full-scale trial. Aim 4 will explore the validity of neuroimaging for quantifying the effects of CPAP on the brain by correlating 1 year changes in neuroimaging biomarkers [hippocampal volume (primary), regional brain volume and thickness, hippocampal subfield volumes, ischemic lesion volume, and cerebral blood flow], with 1 year clinical changes. These results will inform the neuroimaging outcome measures for a full-scale trial. The primary goal of the proposed research is to determine effect size and the feasibility of the study design and methods for a full-scale trial that will determine whether treatment of OSA in oaMCI delays cognitive decline and preserves everyday function. Additional potential study benefits are increased understanding of the physiological mechanisms for cognitive decline in oaMCI and OSA, and the characteristics of those most likely to benefit from this treatment.