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; 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）患者具有认知障碍和 阿尔茨海默氏病（AD）生物标志物（如淀粉样蛋白β和TAU）的增加。正气压正压（PAP） 治疗是OSA的有效治疗方法，但通常受到次优依从性的限制。轶事证据表明 短期和长期适用的OSA治疗改进的注意力，精神运动速度，记忆和 执行功能定义与OSA相关。但是，关于OSA影响的数据稀缺 黑人对神经认知结果的治疗 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 量身定制的“个性化多模式OSA治疗”对黑人的OSA治疗不足 通过提供任何PAP，口服器具疗法的组合，降低少数社区的健康风险 （燕麦）和位置疗法，以及通过无成本解决个人和系统级障碍 入学，个性化的教育/教学用途以及实时依从性监控，导致 有效减少AHI。使用前后治疗设计，我们将检查个性化的多模式 OSA治疗对受试者内部变化i）神经退行性的生物标志物（AIM 1），II） 依赖睡眠的空间导航记忆和功能磁共振成像（fMRI）（AIM 2），并且 iii）检查在12个月时AHI的足够持续减少（有效AHI <15）是否与 全球认知，标准声明记忆，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个性化的多模式的有效AHI降低程度 OSA治疗将预测：1。过夜血浆NFL的纵向变化； 2。纵向变化 脑电路活动和空间航行记忆改善和3。 在12个月的睡眠和认知表现中。我们将利用我们睡眠差异工作组的成功 从少数社区招募以及与会员睡眠诊所的合作并测试我们的中央 在60个新诊断的现代至重度OSA黑色受试者45-75岁的新诊断的新诊断的样本中。受试者会 接受完整的临床评估，神经心理学测试和临床实验室。 3个月之前和之后 个性化的多模式OSA治疗，所有受试者都会经历一个晚上的LAB多聚会摄影术， MR扫描仪中的睡眠前和睡眠后血液抽血和空间导航记忆测试。一个12个月的后续 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，我们将获得并探索确定健康的社会结构决定者（SDOH）因素 与持续的治疗依从性有关，以告知针对临床和公共卫生实践 OSA治疗对黑人认知的依从性和影响不足。