Cognitive decline among WTC survivors with chronic mental and physical disorders

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建筑物产生的大量尘埃云， 以及在随后的几个月里长期暴露于再悬浮的灰尘和烟雾。许多人还 当他们目睹死亡和肢解时，创伤性心理暴露， 他们失去了生活，失去了生计，或者流离失所。创伤后应激障碍的发病率很高 创伤后应激障碍（PTSD），慢性肺部疾病，以及WTC幸存者中的多种癌症。世贸中心参加者 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 灰尘和烟雾暴露已被证明与精神-身体障碍有关，包括创伤后应激障碍， 呼吸系统疾病和癌症。重要的是，最近， 对WTC反应者进行了广泛研究和广泛报道;然而，对WTC幸存者知之甚少。我们 假设来自WTC暴露的氧化应激和相关的全身炎症是 精神和身体疾病共病的生物学机制， 神经炎症、神经变性和认知障碍。迄今为止 暴露于WTC的生物学机制、普遍存在的精神和身体共病疾病，以及 在世贸中心幸存者中还没有调查认知障碍和随时间的下降，导致 知识差距和相当大的不确定性，诊断和评估健康疾病， 幸存者改善诊断和治疗，并确定这些健康问题的生物学基础， 我们提出了一项纵向研究，以评估认知功能和随时间变化的速度， WTC幸存者在WTC EHC登记，并测量全身炎症的血液生物标志物， 神经炎症和神经变性。我们将进行因果推理，分析现有的病人水平， WTC暴露和共病心身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，以评估共病状况和炎症的影响， 血液中的神经变性生物标志物作为认知障碍的WTC暴露的介质， 在整个研究人群和弱势亚群中，认知能力都随着时间的推移而下降。研究 旨在了解复杂的WTC暴露如何影响共病精神和 WTC幸存者的身体障碍和影响认知功能障碍。完成这个项目可能会导致 用于非侵入性准确疾病诊断的新型血液生物标志物的鉴定和成本- 有效监测以及有效干预的潜在目标。

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.