Burden and change in Alzheimers disease neuropathology in aging World Trade Center responders

世贸中心老龄化响应人员中阿尔茨海默病神经病理学的负担和变化

基本信息

批准号：
10577742
负责人：
SEAN CLOUSTON
金额：
$ 79.38万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-15 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10577742
关键词：
Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease related dementia American Amyloid Amyloid beta-Protein Amyloid deposition Biological Markers Blood Brain Brain imaging Case/Control Studies Chronic Post Traumatic Stress Disorder Clinical Clinical Trials Cognitive Cognitive aging Data Deposition Diagnosis Disease Dust Early Onset Alzheimer Disease Education Ethnic Origin Etiology Event Exposure to Feasibility Studies Funding Health Impaired cognition Incidence Individual Inflammatory Life Ligands Light Link Magnetic Resonance Magnetic Resonance Imaging Measures Medical Minority Monitor National Institute on Alcohol Abuse and Alcoholism Nature Nerve Degeneration Neurobehavioral Manifestations Neurocognitive Neurodegenerative Disorders Occupations Olfactory Cortex Pathogenesis Patients Pattern Peripheral Physical Function Pituitary Gland Plasma Population Positron-Emission Tomography Post-Traumatic Stress Disorders Prognosis Proliferating Prospective Studies Proteins Proteomics Protocols documentation Quality of life Race Recording of previous events Recovery Research Sampling Severities Site Staging Stressful Event Symptoms Tauopathies Temporal Lobe Thick Trauma Visit Woman age related aged blood-based biomarker cognitive testing cohort critical period disease classification entorhinal cortex expectation experience follow-up imaging biomarker improved in vivo longitudinal positron emission tomography men middle age mild cognitive impairment molecular imaging neurofilament neuroimaging neuroinflammation neuropathology operation particle physically handicapped programs recruit response sex stressor structural imaging symptomatology tau Proteins treatment response

项目摘要

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 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. Given the magnitude and scale of events surrounding 9/11 and the level of exposure within a young civilian population, prior studies are insufficient in determining the pathogenesis of MCI in the WTC responder cohort. We propose that MCI is arising early because PTSD causes a neuroinflammatory response resulting in increased activation of the pituitary gland resulting in increased Alzheimer’s disease neuropathology. We propose to conduct a large longitudinal PET/MRI study of 120 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. Proteomic analyses will be completed to track changes and to validate a monitoring program for biomarkers in this population. This study is timely because we are in a critical period when neuropathology is still emerging.

抽象的世界贸易中心 (WTC) 救援人员在参与救援时暴露在微小灰尘颗粒的混合物中 2001 年 9 月 11 日之后世贸中心的恢复工作继续受到影响。由于他们的经历而导致的创伤性应激障碍（PTSD）可能改变了他们的期望。我们的团队研究了认知衰老早期迹象的可能性，并发现了这一点。轻度认知障碍（MCI）的负担高于预期，并且令人惊讶的是，身体功能发生变化限制（PFL）在身体残疾和神经退行性疾病中都很常见。围绕 9/11 事件的规模以及年轻平民群体中的暴露程度，先前的研究显示不足以确定 WTC 应答者队列中 MCI 的发病机制，我们认为 MCI 正在出现。早期因为 PTSD 会引起神经炎症反应，导致垂体激活增加导致阿尔茨海默病神经病理学的增加，我们建议进行大型纵向 PET/MRI。使用两种经过充分验证的正电子发射断层扫描 (PET) 对 120 名身体健康的世贸中心响应者进行了研究配体（[11C]-PiB 用于测量 β-淀粉样蛋白，[18F]-Flortaucipir 用于测量 tau 蛋白病）。将有助于确定认知功能障碍的水平，同时结构 MRI 将用于测量将完成蛋白质组学分析以跟踪变化并验证监测。这项研究是及时的，因为我们正处于一个关键时期。神经病理学仍在兴起。