Treatment of OSA on sleep-dependent memory and blood biomarkers in blacks

项目总结。 越来越多的证据表明，阻塞性睡眠呼吸暂停(OSA)患者除了有认知障碍外，还存在认知障碍 阿尔茨海默病(AD)生物标志物的增加，如淀粉样β蛋白和tau。气道正压(PAP) 治疗是治疗阻塞性睡眠呼吸暂停综合征的有效方法，但往往受到依从性不佳的限制。坊间证据显示 短期和长期适当的OSA治疗可以改善注意力、精神运动速度、记忆力和 与阻塞性睡眠呼吸暂停相关的执行功能缺陷。然而，关于OSA的影响的数据很少 黑人的治疗对神经认知结果的影响，尽管OSA和AD的负担不成比例， 以及传统上较低的治疗依从性。在这项创新的假设驱动的研究中，我们将解决 黑人对阻塞性睡眠呼吸暂停治疗的坚持不足，为他们量身定做的个性化多模式阻塞性睡眠呼吸暂停治疗 通过提供PAP、口腔矫治器疗法的任意组合来降低微型化社区的健康风险 (燕麦片)和体位疗法，以及通过免费解决个人和系统层面的障碍 注册、个性化教育/教学使用和实时遵守监控，从而实现 有效地降低了呼吸暂停低通气指数。使用前后处理设计，我们将检查个性化的多模式 OSA治疗对受试者内部变化的影响I)神经变性的血液生物标记物(目标1)，II 睡眠依赖的空间导航记忆和功能磁共振成像(目标2)，以及 三)检查AHI在12个月时的适当持续减少(有效AHI和15)是否与以下因素有关 全球认知、标准陈述性记忆、注意力和处理速度测试的持续改善 (目标3)。我们的中心假设是，我们的个性化多模式有效降低AHI的程度 OSA治疗可预测：1.过夜血浆NFL的纵向变化；2. 脑回路活动与空间导航记忆改善；3.持续改善程度 在12个月的睡眠和认知表现方面。我们将利用我们睡眠差异工作组的成功 从小规模社区招聘，以及与附属睡眠诊所的合作，并测试我们的中央 对60名年龄在45-75岁的新诊断的中到重度阻塞性睡眠呼吸暂停综合征黑人受试者的假设。研究对象将 接受全面的临床评估、神经心理测试和临床实验室。在3个月之前和之后 个性化的多模式阻塞性睡眠呼吸暂停治疗，所有受试者将接受一晚的实验室多导睡眠监测 睡前、睡后抽血及空间导航记忆检查。为期12个月的跟踪调查- UP还将评估睡眠持续改善对认知表现变化的影响。 重要的是，我们将获取并探索确定健康的社会结构决定因素(SDOH)因素 与持续的治疗依从性有关，以告知临床和公共卫生实践 阻塞性睡眠呼吸暂停治疗对黑人认知的影响及依从性不足。

PROJECT SUMMARY. Growing evidence suggests that obstructive sleep apnea (OSA) patients have cognitive impairments as well as increases in Alzheimer's disease (AD) biomarkers such as amyloid beta and tau. Positive airway pressure (PAP) therapy is an effective treatment for OSA but is often limited by suboptimal adherence. Anecdotal evidence show both short and long-term adequate OSA treatment improving attention, psychomotor speed, memory and executive function deficits associated with OSA. However, there is scarcity of data regarding the impact of OSA treatment among blacks on neurocognitive outcomes, despite having a disproportionate burden of OSA and AD, as well as a traditionally low treatment adherence. In this innovative hypothesis-driven study, we will address inadequate adherence to OSA treatment in blacks with “personalized multi-modal OSA treatment”, tailored to reduce health risks in minoritized communities by offering any combination of PAP, oral appliance therapy (OAT) and positional therapy, as well as address individual and system-level barriers through no-cost enrollment, personalized educational/instructional use, and real-time adherence monitoring that results in an effective reduction in AHI. Using a pre-and-post treatment design, we will examine the personalized multi-modal OSA treatment effect on within-subject changes on i) blood-based biomarkers of neurodegeneration (Aim 1), ii) sleep-dependent spatial navigational memory and functional magnetic resonance imaging (fMRI) (Aim 2), and iii) examine whether adequate sustained reductions in AHI at 12 months (effective AHI<15) are associated with sustained improvement in global cognition, standard declarative memory, attention and processing speed tests (Aim 3). Our central hypothesis is that the degree of effective AHI reduction by our personalized multi-modal OSA treatment will predict: 1. the longitudinal change in overnight plasma NfL; 2. the longitudinal change in brain circuit activity and spatial navigational memory improvement and 3. the degree of sustained improvements in sleep and cognitive performance at 12-months.We will leverage the success of our Sleep Disparity Workgroup in recruiting from minoritized communities, and the collaboration with affiliated sleep clinics and test our central hypothesis in a sample of 60 newly diagnosed moderate-to-severe OSA black subjects ages 45-75. Subjects will undergo full clinical evaluation, neuropsychological tests and clinical labs. Prior to and after 3-months of personalized multi-modal OSA treatment, all subjects will undergo a night of in-lab polysomnography with a pre-sleep and post-sleep blood draw and spatial navigational memory test in the MR scanner. A 12-month follow- up will also assess the effect of sustained improvements in sleep on changes in cognitive performance. Importantly, we will acquire and explore identifying socio-structural determinants of health (SDOH) factors that are associated with sustained treatment adherence to inform both clinical and public health practices targeting inadequate adherence and impact of OSA treatment on cognition in blacks.