Cognitive decline among WTC survivors with chronic mental and physical disorders

患有慢性精神和身体疾病的世贸中心幸存者认知能力下降

• 批准号: 10683779
• 负责人: JOAN REIBMAN
• 金额: $ 60万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10683779
• 关键词: Cognitive; decline; among; WTC; survivors

Project Summary The World Trade Center Environmental Health Center (WTC EHC) is a NIOSH-designated treatment and monitoring program for community members (“WTC Survivors”) with acute and/or chronic WTC exposures. Physical exposures include acute exposures to the massive dust clouds from the collapsing WTC buildings as well as chronic exposures to the resuspended dust and fumes in the subsequent months. Many also had traumatic psychological exposures as they witnessed death and dismemberment, worried about their own safety, lost their livelihood, or were displaced. There is a high prevalence of post-traumatic stress disorder (PTSD), chronic pulmonary disorder, and many types of cancers among WTC Survivors. Enrollees of WTC EHC include about 50% women and have diverse social-economic and racial/ethnic backgrounds. The WTC dust and fume exposures have been shown to be associated with mental-physical disorders, including PTSD, respiratory disorders, and cancers. Importantly, increased cognitive impairments have recently been extensively studied and widely reported for WTC responders; however, little is known for WTC Survivors. We hypothesize that the oxidative stress from the WTC exposures and affiliated systemic inflammation are part of the biological mechanism underlying the comorbid mental and physical disorders and contributing to neuroinflammation, neurodegeneration, and cognitive impairments in many WTC Survivors. To date, the biological mechanism underlying the WTC exposures, prevalent comorbid mental and physical disorders, and cognitive impairments and decline over time have not been investigated in WTC Survivors, leading to knowledge gaps and considerable uncertainty in both diagnosis and assessment of health disorders for Survivors. To improve diagnosis and treatment and to identify the biological underpinning of these health disorders, we propose a longitudinal study to assess cognitive functions and rate of changes over time among WTC Survivors enrolled at WTC EHC and also measure blood-based biomarkers of systemic inflammation, neuroinflammation, and neurodegeneration. We will conduct causal inference to analyze existing patient-level WTC exposures and comorbid mental-physical disorders data together with newly obtained cognitive scores and blood-based biomarker data to assess the effect of comorbid conditions and inflammation and neurodegeneration biomarkers in blood as mediators of the WTC exposures for cognitive impairments and cognitive decline over time both in the whole study population and in vulnerable subpopulations. The study aims to understand the biological mechanisms of how complex WTC exposures affect comorbid mental and physical disorders and impact cognitive dysfunctions in WTC Survivors. Completing this project may lead to the identification of novel blood-based biomarkers for non-invasive accurate disease diagnosis and cost- effective monitoring as well as potential targets for effective intervention.

项目摘要 世界贸易中心环境卫生中心（WTC EHC）是NIOSH指定的治疗方法 急性和/或慢性WTC暴露的社区成员（“ WTC幸存者”）的监测计划。 物理暴露包括从WTC建筑物中崩溃的大量尘埃云的急性暴露 以及在随后的几个月中慢性暴露于恢复的灰尘和烟雾中。许多人也有 当他们目睹死亡和肢解时，创伤性心理暴露，担心自己的 安全，失去生计或流离失所。创伤后应激障碍患病率很高 WTC幸存者中（PTSD），慢性肺疾病和许多类型的癌症。 WTC的注册 EHC包括约50％的妇女，并具有潜水员的社会经济和种族/种族背景。 WTC 尘埃和烟气暴露已被证明与包括PTSD在内的精神物理疾病有关 呼吸系统疾病和癌症。重要的是，最近的认知障碍增加了 对WTC响应者进行广泛研究，并广泛报告；但是，WTC幸存者闻名很少。我们 假设WTC暴露和会员全身注入的氧化应激是 合并症的精神和身体疾病的基础生物学机制，并为 许多WTC幸存者中的神经炎症，神经退行性和认知障碍。迄今为止， WTC暴露，普遍存在的精神和身体疾病以及 WTC幸存者尚未研究认知障碍和随着时间的流逝下降，导致 诊断和健康障碍评估的知识差距和相当大的不确定性 幸存者。改善诊断和治疗并确定这些健康的生物学基础 疾病，我们提出了一项纵向研究，以评估随着时间的推移的认知功能和变化的速度 WTC幸存者参加了WTC EHC，还测量了系统性炎症的血液生物标志物， 神经炎症和神经变性。我们将进行因果推论以分析现有的患者级 WTC暴露和合并的精神物理障碍数据以及新获得的认知分数 以及基于血液的生物标志物数据，以评估合并症和注射的影响 血液中的神经变性生物标志物作为WTC暴露于认知障碍和 在整个研究人群和脆弱的亚人群中，随着时间的流逝，认知能力下降。研究 旨在了解复杂的WTC暴露如何影响合并症和精神的生物学机制 WTC幸存者的身体疾病和影响认知功能障碍。完成此项目可能会导致 鉴定新型血液基于非侵入性准确疾病诊断诊断和成本 - 成本的生物标志物 有效监测以及有效干预的潜在目标。