Physical and mental health pathways to cognitive decline in World Trade Center responders: The roles of pulmonary function and post-traumatic stress disorder

摘要 为了响应RFA-OH-21-004，我们探索了WTC暴露与认知功能之间的关系。 通过身体和精神健康状况的非认知途径下降，特别是异常 肺量测定和慢性创伤后应激障碍该项目将回答与长期影响有关的关键问题 身体和精神健康状况，并进一步扩大我们对非认知 导致认知能力下降的途径。 世界贸易中心的救援人员已经被证明经历了快速的身体衰老，精神健康状况不佳 结果，以及最近的认知障碍的早期发作。早发性认知障碍可能是 通过表现为非认知症状的机制运作。肺功能异常和慢性 创伤性应激障碍（PTSD）是两种高度流行和普遍的身体和精神健康状况 在WTC反应者中，可能表明潜在的认知能力下降。事实上， 911恐怖袭击，随着这群人进入老年， 认知能力下降不仅会为预防工作提供信息，而且还会为高风险患者的专门干预提供信息。 个体 这个项目将使用来自斯托尼布鲁克大学世界贸易中心健康项目的二级数据 (SBU WTC-HP，R01 AG049953）。目的1将检验肺量测定异常的联合效应 慢性PTSD对认知功能下降的影响大于其个体效应。目标2将调查 肺功能异常和慢性PTSD单独或联合介导相关性的程度 WTC暴露和认知能力下降之间的联系 我们团队以前的工作支持这个项目：我们以前已经证明， 功能和身体功能共同下降;我们已经表明，呼吸道症状和慢性PTSD 在WTC反应者中经常共同发生;我们已经表明，慢性PTSD是早期- WTC应答者的认知障碍发作。这些发现指向一个共同的潜在机制 影响这些条件和结果;然而，需要进一步调查，以确定慢性和 从WTC暴露到认知能力下降的路径。 在这个项目中，我们将系统地研究从世界贸易中心到非认知的直接和间接路径 暴露于认知能力下降，以改善对特定非认知能力下降的个体的识别 导致认知障碍的途径这将最终导致预防工作，以减轻 通过治疗非认知症状来预防认知障碍。

ABSTRACT In response to RFA-OH-21-004, we explore the association between WTC exposure and cognitive decline via non-cognitive pathways of physical and mental health conditions, specifically abnormal spirometry and chronic PTSD. This project will answer critical questions relating to long-term effects of physical and mental health conditions, and further expand our knowledge on non-cognitive pathways that lead to cognitive decline. World Trade Center responders have been shown to experience rapid physical aging, poor mental health outcomes, and more recently, early onset of cognitive impairment. Early onset cognitive impairment may be operating via mechanisms that manifest as non-cognitive symptoms. Abnormal spirometry and chronic post- traumatic stress disorder (PTSD) are two highly prevalent and pervasive physical and mental health conditions in WTC responders that may be indicative of insidious cognitive decline. Indeed, it has been two decades since the September 11th terrorist attacks, and as this cohort moves into older age, disentangling specific pathways to cognitive decline will inform not only on preventative efforts but also on specialized interventions in high risk individuals. This project will use secondary data from the Stony Brook University World Trade Center Health Program (SBU WTC-HP, R01 AG049953). Aim 1 will test the hypothesis that the joint effects of abnormal spirometry and chronic PTSD on cognitive decline are larger than their individual effects. Aim 2 will then investigate the extent to which abnormal spirometry and chronic PTSD individually and conjointly mediate the association between WTC exposure and cognitive decline. Compelling previous work from our team supports this project: We have previously shown that cognitive function and physical function decline co-jointly; we have shown that respiratory symptoms and chronic PTSD in WTC responders co-occur frequently; and we have shown that chronic PTSD is in the pathway to early- onset cognitive impairment in WTC responders. These findings point towards a shared underlying mechanism affecting these conditions and outcomes; however, further investigation is needed to determine chronicity and paths from WTC exposure to cognitive decline. In this project, we will systemically examine the direct and indirect non-cognitive paths from WTC exposure to cognitive decline to improve identification of individuals who are on specific non-cognitive pathways to cognitive impairment. This will eventually lead to prevention efforts to mitigate preventable cognitive impairment by treating non-cognitive symptoms.