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

OSA 治疗对黑人睡眠依赖性记忆和血液生物标志物的影响

• 批准号: 10740142
• 负责人: OMONIGHO A MICHAEL Bubu
• 金额: $ 253.14万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10740142
• 关键词: Accounting; Address; Adherence; African American population; Aftercare; Age; Alzheimer' s Disease; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amygdaloid structure; Amyloid beta-Protein; Apnea; Area; Attention; Biological Markers; Black Populations; Blood; Blood Pressure; Brain; Brain Injuries; Clinic; Clinical; Cognition; Collaborations; Data; Discrimination; Disparity; Education; Enrollment; Event; Executive Dysfunction; Exhibits; Fibrinogen; Functional Magnetic Resonance Imaging; Goals; Health; High Prevalence; Hippocampus; Hour; Hypertension; Impaired cognition; Impairment; Individual; Instruction; Investigation; Measures; Memory; Minority Recruitment; Monitor; Nerve Degeneration; Neurocognitive; Neurocognitive Deficit; Neuropsychological Tests; Newly Diagnosed; Obstructive Sleep Apnea; Oral Positive Airway Pressure; Outcome; Patients; Performance; Pharmaceutical Preparations; Pilot Projects; Plasma; Polysomnography; Prevalence; Protein Isoforms; Public Health; Public Health Practice; Regimen; Risk; Sampling; Severities; Sleep; Sleep Apnea Syndromes; Sleep Stages; Social support; Socioeconomic Factors; Speed; Testing; Time; adverse outcome; blood-based biomarker; cognitive performance; cost; effective therapy; follow-up; health care availability; improved; indexing; innovation; minority communities; multimodality; positive airway pressure; prevent; processing speed; psychosocial; research clinical testing; social health determinants; social influence; social structure; structural health determinants; success; system-level barriers; tau Proteins; therapy design; treatment adherence; treatment effect; way finding

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.

项目摘要。 越来越多的证据表明，阻塞性睡眠呼吸暂停 (OSA) 患者存在认知障碍以及 阿尔茨海默病 (AD) 生物标志物，例如β-淀粉样蛋白和 tau 蛋白，气道正压通气 (PAP) 增加。 治疗是 OSA 的有效治疗方法，但经常受到依从性不佳的限制。 短期和长期充分的 OSA 治疗可改善注意力、精神运动速度、记忆力和 与 OSA 相关的执行功能缺陷 然而，有关 OSA 影响的数据很少。 尽管黑人患有 OSA 和 AD 的负担不成比例，但对神经认知结果的治疗 以及传统上治疗依从性较低的问题。在这项创新的假设驱动研究中，我们将解决这一问题。 通过“个性化多模式 OSA 治疗”，黑人对 OSA 治疗的依从性不足 通过提供 PAP、口腔矫治器治疗的任意组合来降低少数群体的健康风险 （OAT）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/教学使用以及实时依从性监控，从而实现 使用治疗前和治疗后设计，我们将检查个性化多模式。 OSA 治疗对受试者内 i) 神经变性血液生物标志物变化的影响（目标 1），ii) 睡眠依赖性空间导航记忆和功能磁共振成像 (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 整体认知、标准陈述性记忆、注意力和处理速度测试持续改善 （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 治疗将预测： 1. 夜间血浆 NfL 的纵向变化； 2. 3.脑回路活动和空间导航记忆的改善和持续改善的程度 12 个月大时的睡眠和认知表现。我们将利用睡眠差异工作组的成功 从少数族裔社区招募人员，以及与附属睡眠诊所合作并测试我们的中心 假设 60 名新诊断的中度至重度 OSA 黑人受试者年龄为 45-75 岁。 在 3 个月之前和之后接受全面的临床评估、神经心理学测试和临床实验室。 个性化多模式 OSA 治疗，所有受试者都将接受一晚的实验室多导睡眠图检查 睡前和睡后抽血以及 MR 扫描仪的空间导航记忆测试 12 个月的随访。 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 与持续治疗依从性相关，以告知临床和公共卫生实践 OSA 治疗依从性不足及其对黑人认知的影响。