Mild Cognitive Impairment and Obstructive Sleep Apnea

描述(申请人提供)：轻度认知障碍(MCI)，以记忆障碍为特征，但日常功能很少或没有下降，是介于正常衰老和阿尔茨海默病(AD)之间的过渡阶段。每年有高达15%的患有MCI(OaMCI)的老年人转变为AD。在oaMCI患者中，很少有干预措施能有效延缓认知衰退并保护日常功能。然而，治疗并存的阻塞性睡眠呼吸暂停(OSA)可能有可能延缓认知能力下降。大约60%患有MCI和早期AD的老年人患有OSA，而普通人群中这一比例仅为7%-18%。OSA的特征是间歇性的夜间上呼吸道塌陷，伴随呼吸减少和/或停止，导致缺氧、睡眠片断、日间嗜睡和认知功能障碍。持续气道正压(CPAP)是一种睡眠时佩戴的加压鼻罩，可以有效地治疗阻塞性睡眠呼吸暂停综合征，但关于其在这一人群中的疗效信息很少。对于oaMCI合并CPAP治疗阻塞性睡眠呼吸暂停是否延缓认知功能衰退并保留日常生活功能的问题，目前还没有人给出答案。在目标1中，我们将进行一项为期6个月的随机对照临床试验，以评估主动CPAP(n=75)与假CPAP(n=35)对患有遗忘性轻度认知障碍和OSA的老年人认知和日常功能的影响。然后，我们建议在一项开放标签试验中，对积极的CPAP组再跟踪6个月，以评估与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的使用时间。在目标2中，我们将探讨CPAP治疗的依从性、控制基线的OSA严重程度、既往存在脑血管疾病和缺氧缺血性脑损伤的神经影像证据、载脂蛋白E4以及先前确定的人口统计学和其他患者因素是否能预测CPAP活动1年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。目的通过将1年来神经影像生物标志物[海马体积(初级)、局部脑体积和厚度、海马子区体积、缺血灶体积和脑血流量]与1年临床变化的相关性，探讨神经影像在量化CPAP对脑的影响方面的有效性。这些结果将为全面试验的神经成像结果测量提供依据。这项拟议研究的主要目标是确定OSA在oaMCI中的疗效大小以及研究设计和方法的可行性，以确定OSA在oaMCI中的治疗是否延缓认知衰退并保留日常功能。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，以及那些最有可能从这种治疗中受益的人的特征。

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.