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.

项目概要 世界贸易中心环境健康中心 (WTC EHC) 是 NIOSH 指定的治疗和治疗中心 针对急性和/或慢性接触世贸中心的社区成员（“世贸中心幸存者”）的监测计划。 物理暴露包括严重暴露于倒塌的世贸中心大楼产生的大量尘埃云中， 在接下来的几个月里，许多人还长期暴露在重新悬浮的灰尘和烟雾中。 当他们目睹死亡和肢解时，他们会遭受创伤性心理暴露，担心自己的生命 安全、失去生计或流离失所。创伤后应激障碍的患病率很高。 WTC 幸存者中的创伤后应激障碍 (PTSD)、慢性肺部疾病和多种癌症。 EHC 包括约 50% 的女性，并且拥有多元化的社会经济和种族/民族背景。 灰尘和烟雾暴露已被证明与身心疾病有关，包括创伤后应激障碍（PTSD）、 重要的是，认知障碍最近有所增加。 对世贸中心响应者进行了广泛研究和广泛报道；然而，对世贸中心幸存者却知之甚少。 来自世贸中心暴露的氧化应激和相关的全身炎症是其中的一部分 共病精神和身体疾病的生物学机制并有助于 迄今为止，许多世贸中心幸存者都出现了神经炎症、神经退行性疾病和认知障碍。 WTC 暴露背后的生物学机制、普遍存在的精神和身体疾病共病，以及 认知障碍和随着时间的推移而下降的情况尚未在世贸中心幸存者中进行调查，导致 健康障碍的诊断和评估方面存在知识差距和相当大的不确定性 改善幸存者的诊断和治疗并确定这些健康的生物学基础。 疾病，我们提出一项纵向研究来评估认知功能和随时间变化的速度 WTC 幸存者参加了 WTC EHC，还测量了全身炎症的血液生物标志物， 我们将进行因果推断来分析现有的患者水平。 WTC 暴露和共病精神身体疾病数据以及新获得的认知评分 和基于血液的生物标志物数据，以评估共病和炎症的影响， 血液中的神经退行性生物标志物作为认知障碍 WTC 暴露的介质 随着时间的推移，整个研究人群和弱势亚人群的认知能力都会下降。 旨在了解复杂的世贸中心暴露如何影响共病心理和疾病的生物学机制 完成该项目可能会导致世贸中心幸存者的身体障碍和认知功能障碍。 识别新型血液生物标志物，用于非侵入性准确疾病诊断和成本 有效的监测以及有效干预的潜在目标。