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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：
10371245
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/10371245
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 Women Molecular Monitor 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 Prospective Studies Proteins Proteomics Protocols documentation Quality of life Race Recording of previous events Recovery Research Severities Site Staging Stressful Event Symptoms Tauopathies Temporal Lobe Thick Time Visit Woman age related aged base blood-based biomarker cognitive testing cohort critical period entorhinal cortex expectation experience follow-up imaging biomarker improved in vivo longitudinal positron emission tomography men middle age mild cognitive impairment neurofilament neuroimaging neuroinflammation neuropathology operation particle physically handicapped programs recruit response sex stressor 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.

摘要