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

项目摘要。 越来越多的证据表明，阻塞性睡眠呼吸暂停（OSA）患者有认知障碍，以及 阿尔茨海默病（AD）生物标志物如淀粉样蛋白β和tau蛋白的增加。气道正压通气（PAP） 治疗是对OSA的有效治疗，但经常受到次优依从性的限制。传闻证据表明 短期和长期适当的OSA治疗，改善注意力，精神速度，记忆力和 与OSA相关的执行功能缺陷。然而，关于阻塞性睡眠呼吸暂停综合征的影响的数据很少 在黑人中进行神经认知结果的治疗，尽管有不成比例的OSA和AD负担， 以及传统的低治疗依从性。在这项创新的假设驱动的研究中，我们将解决 在黑人中使用“个性化多模式OSA治疗”， 通过提供PAP、口腔矫治器治疗的任何组合， (OAT)和位置疗法，以及解决个人和系统层面的障碍，通过无成本 注册、个性化教育/教学使用和实时依从性监控， 有效降低AHI。使用前和后处理设计，我们将研究个性化的多模态 OSA治疗对受试者内变化的影响：i）基于血液的神经变性生物标志物（目的1），ii） 睡眠依赖性空间导航记忆和功能性磁共振成像（fMRI）（目标2），以及 iii）检查12个月时AHI的充分持续降低（有效AHI<15）是否与以下因素相关： 持续改善整体认知、标准陈述性记忆、注意力和处理速度测试 (Aim 3）。我们的中心假设是，通过我们的个性化多模式治疗， OSA治疗将预测：1。过夜血浆NfL的纵向变化; 2.纵向变化 脑回路活动和空间导航记忆改善; 3.持续改善的程度 在12个月的睡眠和认知表现。我们将利用我们的睡眠差异工作组的成功 从少数民族社区招募，并与附属睡眠诊所合作，测试我们的中心 在60名年龄为45-75岁的新诊断的中度至重度OSA黑人受试者的样本中，受试者将 接受全面的临床评估、神经心理测试和临床实验室检查。3个月之前和之后 个性化的多模式OSA治疗，所有受试者将接受一个晚上的实验室多导睡眠图， 睡眠前和睡眠后抽血和MR扫描仪中的空间导航记忆测试。12个月后， up还将评估睡眠持续改善对认知能力变化的影响。 重要的是，我们将获得和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相关，以告知临床和公共卫生实践， 在黑人中，OSA治疗依从性不足和对认知的影响。

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.