Cognition and neuropathology in World Trade Center-exposed FDNY, NYPD, and construction worker responders

摘要 世界贸易中心（WTC）的救援人员在参与救援时暴露在微小的尘埃颗粒中 2001年9月11日之后，世贸中心的重建工作。许多人继续遭受后... 创伤性应激障碍（PTSD）是他们经历的结果。这些可能改变了他们的预期 大脑健康的变化。我们的团队已经研究了认知老化早期迹象的可能性， 发现轻度认知障碍（MCI）的负担高于预期，令人惊讶的是， 功能限制（PFL）常见于身体残疾和神经退行性疾病。我们提出 MCI的早期出现是因为PTSD和吸入颗粒物暴露导致了神经退行性疾病， 疾病，导致阿尔茨海默病神经病理学增加。我们建议进行一项大型研究， 暴露于WTC的纽约市消防局（FDNY）响应人员，包括认知功能 与基于血液的生物标志物的最先进的蛋白质组学研究一起进行分析， 使用两种经过充分验证的正电子发射断层扫描（PET）配体的30名医学健康WTC应答者 （[11 C]-PiB测量β-淀粉样蛋白，[18 F]-Flortaucipir测量tau蛋白病）。详细的认知测试将有助于 来确定认知功能障碍的程度将使用同步结构MRI测量 神经退行性疾病这项研究是及时的，因为我们正处于神经病理学的关键时期， 新出现的和疾病的病因仍有可能确定。

Abstract World Trade Center (WTC) responders were exposed to a mix of tiny dust particles as they participated in rescue and recovery efforts at the WTC in the aftermath of 9/11/2001. A significant number continue to suffer from Post- Traumatic Stress Disorder (PTSD) as a result of their experiences. These may have changed their expectations of brain health as they age. Our team has interrogated the potential for early signs of cognitive aging and has identified higher than expected burden of mild cognitive impairment (MCI) and, surprisingly, changes to physical functional limitations (PFL) common in both physical disability and in neurodegenerative disease. We propose that MCI is arising early because PTSD and inhaled particulate exposures have caused a neurodegenerative disease, resulting in increased Alzheimer’s disease neuropathology. We propose to conduct a large study of WTC-exposed Fire Department of the City of New York (FDNY) responders that includes cognitive functioning profiling alongside state-of-the-art proteomic studies of blood-based biomarkers alongside a PET/MRI study of 30 medically healthy WTC responders using two well-validated positron emission tomography (PET) ligands ([11C]-PiB to measure β-amyloid, and [18F]-Flortaucipir to measure tauopathy). Detailed cognitive testing will help to determine the level of cognitive dysfunction. Simultaneous structural MRI will be used to measure the extent of neurodegeneration. This study is timely because we are in a critical period when neuropathology is emerging and the etiology of the disease is still possible to determine.