Sleep stability, emotional memory and risk for neurodegeneration in World Trade Center Responders

世贸中心急救人员的睡眠稳定性、情绪记忆和神经退行性变风险

• 批准号: 10749687
• 负责人: Anna Mullins
• 金额: $ 24.99万
• 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: 2023-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10749687
• 关键词: Sleep; stability; emotional; memory; risk

Project Summary World Trade Center (WTC) Responders self-report high levels of poor sleep quality and exhibit a high prevalence of sleep disorders such as obstructive sleep apnea (OSA) and insomnia. Research investigating brain health in this population indicates early-age cognitive impairments and neurodegeneration associated with both physical exposures of particulate neurotoxins at the WTC site and chronic post-traumatic stress disorder (PTSD). There is evidence that poor sleep quality is associated with cognitive impairments, biomarkers of neurodegeneration and dementia in both sleep disorders and the general community. However, it is not known if poor sleep quality contributes to increased risk of neurodegeneration in WTC Responders. Sleep quality is a term that encompasses multiple aspects of sleep initiation, maintenance, quantity, and refreshment upon awakening. It is typically assessed subjectively using questionnaires that evaluate general satisfaction with current sleep-related quality of life, sleep behaviors or symptoms. A potentially useful, and objectively measured, proxy for sleep quality is sleep stability. Metrics of sleep stability can be obtained through the lens of the central nervous system (CNS) with electroencephalography (EEG) or the corresponding autonomic nervous system (ANS) activity using cardiopulmonary coupling (CPC). EEG-measured rapid eye movement (REM) and non-REM (NREM) sleep instability is characteristic of insomnia and OSA. Sleep instability caused by OSA results in impaired sleep-dependent memory and increases in markers of neurodegeneration. Reduced and delayed REM, manifestations of REM instability, are associated with increased risk of dementia in a large community cohort. Quality EEG signals are difficult to obtain at-home but newer, wearable CPC-measuring devices can provide sleep quality and disorder severity measures from the home. CPC measured sleep demonstrates exaggerated night-to-night variability in insomnia. Highly variable sleep schedules predict successful response to treatment with cognitive behavioral therapy for insomnia (CBTi). We plan to enroll 40 WTC Responders who will undergo 2 weeks at-home CPC sleep monitoring followed by an overnight in-lab PSG with pre/post-sleep emotional memory picture task and blood sampling. Aim 1a is to test whether single-night REM sleep instability measured by EEG activity is associated with impaired emotional memory. Exploratory Aim 1b is to test any potential association between impaired overnight memory processing and overnight change in plasma biomarkers Tau and NFL. Aim 2 is to test whether inconsistent sleep quality measured by night-to-night variability in CPC is associated with greater evening plasma Tau and NFL levels.

项目概要 世界贸易中心 (WTC) 的受访者自我报告睡眠质量严重不佳，并表现出较高的睡眠质量 阻塞性睡眠呼吸暂停（OSA）和失眠等睡眠障碍的患病率。研究 对这一人群的大脑健康状况的调查表明，他们存在早期认知障碍和 与世贸中心站点颗粒神经毒素的物理暴露相关的神经变性 和慢性创伤后应激障碍（PTSD）。有证据表明睡眠质量差 与睡眠中的认知障碍、神经退行性变和痴呆症的生物标志物相关 疾病和一般社区。然而，尚不清楚睡眠质量是否会导致 世贸中心响应者神经变性的风险增加。睡眠质量这个术语包括 睡眠启动、维持、数量和醒来时恢复活力的多个方面。这是 通常使用问卷进行主观评估，评估对当前的总体满意度 与睡眠相关的生活质量、睡眠行为或症状。潜在有用且客观的 经测量，睡眠质量的代表是睡眠稳定性。睡眠稳定性指标可以通过以下方式获得 中枢神经系统（CNS）的晶状体与脑电图（EEG）或相应的 使用心肺耦合 (CPC) 的自主神经系统 (ANS) 活动。脑电图快速测量 眼动 (REM) 和非快速眼动 (NREM) 睡眠不稳定是失眠和 OSA 的特征。 OSA 引起的睡眠不稳定会导致睡眠依赖性记忆受损和标记物增加 神经退行性变。 REM 减少和延迟（REM 不稳定的表现）与 在大型社区人群中患痴呆症的风险增加。高质量脑电图信号难以获得 在家使用但较新的可穿戴 CPC 测量设备可以提供睡眠质量和疾病严重程度 从家里采取的措施。 CPC 测量的睡眠表现出夸大的夜间睡眠变化 失眠。高度可变的睡眠时间表预测认知治疗的成功反应 失眠行为疗法（CBTi）。我们计划招募 40 名 WTC 救援人员，他们将接受 2 在家进行数周的 CPC 睡眠监测，然后进行过夜的实验室 PSG（睡眠前/睡眠后） 情绪记忆图片任务和血液采样。目标 1a 是测试单晚快速眼动睡眠是否有效 通过脑电图活动测量的不稳定性与情绪记忆受损有关。探索性目标 1b 是测试夜间记忆处理受损与过夜之间的任何潜在关联 血浆生物标志物 Tau 和 NFL 的变化。目标2是测试睡眠质量是否不一致 通过 CPC 的夜间变异性测量，与晚间血浆 Tau 和 NFL 较高相关 水平。