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 世界贸易中心环境健康中心(WTC EHC)是NIOSH指定的治疗和 对急性和/或慢性WTC暴露的社区成员(“WTC幸存者”)的监测计划。 物理暴露包括急性暴露于世贸中心倒塌建筑产生的大量尘埃云，如 以及在接下来的几个月里长期暴露在再悬浮的粉尘和烟雾中。许多人也有 他们目睹死亡和肢解时的创伤心理暴露，担心自己 安全，失去生计，或流离失所。创伤后应激障碍的发病率很高 WTC幸存者中患有创伤后应激障碍(PTSD)、慢性肺部疾病和多种癌症。世界旅游中心的参加者 EHC包括约50%的妇女，具有不同的社会经济和种族/民族背景。世贸中心 粉尘和油烟暴露已被证明与精神-身体疾病有关，包括创伤后应激障碍， 呼吸系统疾病和癌症。重要的是，认知障碍的增加最近 对WTC应答者进行了广泛的研究和广泛的报道；然而，WTC幸存者知之甚少。我们 假设WTC暴露的氧化应激和相关的全身性炎症是 精神和身体疾病并存的生物学机制 许多WTC幸存者的神经炎症、神经变性和认知障碍。到目前为止， WTC暴露的生物学机制，普遍存在的共病精神和身体障碍，以及 WTC幸存者的认知障碍和随着时间的推移而下降的情况尚未得到调查，导致 健康障碍的诊断和评估方面的知识差距和相当大的不确定性 幸存者。改进诊断和治疗，并确定这些健康的生物学基础 ，我们建议进行一项纵向研究，以评估认知功能和随时间变化的速率 WTC幸存者在WTC EHC注册，还测量基于血液的全身炎症生物标志物， 神经炎症和神经变性。我们将进行因果推理来分析现有的患者层面 WTC暴露和共病的精神-身体障碍数据以及新获得的认知分数 和基于血液的生物标志物数据，以评估并存条件和炎症的影响 血液中神经退行性生物标志物作为WTC暴露的认知障碍和 无论是在整个研究人群中，还是在脆弱的亚群中，认知能力都会随着时间的推移而下降。这项研究 旨在了解复杂的WTC暴露如何影响共病精神和精神疾病的生物学机制 WTC幸存者的躯体障碍和影响认知功能障碍。完成这个项目可能会导致 新的血液生物标记物的识别无创性，准确的疾病诊断和成本。 有效监测以及有效干预的潜在目标。