Mild Cognitive Impairment and Obstructive Sleep Apnea

轻度认知障碍和阻塞性睡眠呼吸暂停

• 批准号: 8184631
• 负责人: Kathy Culpepper Richards
• 金额: $ 64.81万
• 依托单位: GEORGE MASON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8184631
• 关键词: Adherence; Adult; Alleles; Alzheimer' s Disease; Behavior Therapy; Bioethics; Biological Markers; Brain; Breathing; Cerebrovascular Circulation; Cerebrovascular Disorders; Characteristics; Clinical; Clinical Trials; Cognitive; Conflict (Psychology); Continuous Positive Airway Pressure; Data; Devices; Double-Blind Method; Elderly; Feasibility Studies; Future; General Population; Goals; Health Personnel; Hippocampus (Brain); Hour; Hypoxia; Impaired cognition; Intervention; Ischemic-Hypoxic Encephalopathy; Masks; Measures; Memory impairment; Methods; Nose; Obstructive Sleep Apnea; Outcome Measure; Participant; Patients; Persons; Physiological; Placebo Control; Placebos; Population; Randomized; Randomized Controlled Trials; Research; Research Design; Sample Size; Severities; Sleep; Staging; Students; Thick; Treatment outcome; apolipoprotein E-4; base; brain volume; design; effective intervention; ischemic lesion; middle age; mild neurocognitive impairment; neuroimaging; normal aging; open label; pilot trial; pressure; sensor; treatment adherence; treatment response

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. PUBLIC HEALTH RELEVANCE: The goal of the research is to determine the power and the feasibility of the study design and methods to inform a full-scale clinical trial that will determine whether treatment of obstructive sleep apnea in older adults with mild cognitive impairment delays cognitive decline and preserves everyday function. We propose to conduct a 6-month double-blind randomized, placebo-controlled pilot clinical trial to compare the effects of active continuous positive airway pressure versus sham continuous positive airway pressure on cognitive and everyday function in 110 older adults with mild cognitive impairment and obstructive sleep apnea. We also will collect pilot data on the 1-year outcomes of treatment of obstructive sleep apnea, and the validity of neuroimaging for measuring clinical change in persons with mild cognitive impairment and obstructive sleep apnea. The results will inform the study design, sample size, participant recruitment and retention methods, and measures for a full-scale trial.

描述（申请人提供）： 轻度认知障碍（MCI），其特征是记忆障碍，但日常功能很少或没有下降，是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。很少有干预措施能有效延缓 oaMCI 认知能力下降并维持日常功能。然而，治疗合并症阻塞性睡眠呼吸暂停（OSA）可能有延缓认知能力下降的潜力。大约 60% 患有 MCI 和早期 AD 的老年人患有 OSA，而普通人群中只有 7-18% 的老年人患有 OSA。OSA 的特点是夜间发作性上呼吸道塌陷，并伴有减少和/或停止呼吸困难，导致缺氧、睡眠碎片、白天嗜睡和认知功能障碍。持续气道正压通气 (CPAP) 是一种在睡眠时佩戴的加压鼻罩，可有效治疗阻塞性睡眠呼吸暂停 (OSA)，但关于其在这一人群中的疗效的信息很少。没有人回答这一问题：使用 CPAP 治疗 oaMCI 患者的 OSA 是否可以延缓认知能力下降并保留日常功能。 在目标 1 中，我们将进行一项为期 6 个月的随机对照试点临床试验，以评估主动 CPAP (n=75) 与假 CPAP (n=35) 相比对患有遗忘性轻度认知的老年人的认知和日常功能的影响大小损伤和 OSA。然后，我们建议在一项开放标签试验中对积极 CPAP 治疗组进行额外 6 个月的跟踪，以估计 CPAP 治疗依从性对认知和日常功能的影响大小。可以使用隐藏的传感器精确测量 CPAP 坚持情况，该传感器确定在规定压力下的使用时间。在目标 2 中，我们将探讨 CPAP 治疗依从性（控制基线 OSA 严重程度、先前存在的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和其他患者因素）是否可以预测 1 年后的认知和日常功能。积极 CPAP 治疗的年份。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，为全面试验提供信息。目标 4 将通过关联神经影像生物标志物 [海马体积（初级）、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）的 1 年变化，探索神经影像用于量化 CPAP 对大脑影响的有效性]，有1年的临床变化。这些结果将为全面试验的神经影像结果测量提供信息。 拟议研究的主要目标是确定效应大小以及研究设计和全面试验方法的可行性，该试验将确定 oaMCI 中 OSA 的治疗是否可以延缓认知能力下降并保留日常功能。其他潜在的研究好处是加深对 oaMCI 和 OSA 认知能力下降的生理机制的了解，以及最有可能从这种治疗中受益的人群的特征。 公共健康相关性：该研究的目标是确定研究设计和方法的效力和可行性，为全面的临床试验提供信息，该试验将确定对患有轻度认知障碍的老年人进行阻塞性睡眠呼吸暂停的治疗是否会延缓认知衰退并保留日常功能。我们建议开展一项为期 6 个月的双盲随机、安慰剂对照试点临床试验，以比较主动持续气道正压通气与假持续气道正压通气对 110 名患有轻度认知障碍和阻塞性老年人的认知和日常功能的影响睡眠呼吸暂停。我们还将收集有关阻塞性睡眠呼吸暂停治疗的 1 年结果的试点数据，以及神经影像学用于测量轻度认知障碍和阻塞性睡眠呼吸暂停患者临床变化的有效性。结果将为研究设计、样本量、参与者招募和保留方法以及全面试验的措施提供信息。