A Life Course Approach to Integrating Trauma and Cognitive Aging: A Cohort of 9/11 Responders

整合创伤和认知老化的生命全程方法：9/11 事件响应者队列

基本信息

批准号：
10623337
负责人：
SEAN CLOUSTON
金额：
$ 158.23万
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：
2015
资助国家：
美国
起止时间：
2015-05-15 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10623337
关键词：
Address Age Alzheimer&apos s Disease Alzheimer&apos s disease related dementia American Amyloid Apolipoproteins Biological Assay Blood Cause of Death Cessation of life Childhood Chronic Chronic Post Traumatic Stress Disorder Climacteric Cognition Cognitive Cognitive aging Craniocerebral Trauma Data Disease Dust Elderly Emotional Encephalopathies Event Exposure to Family Family member Freezing Friends Functional disorder Future Genetic Genetic Carriers Glial Fibrillary Acidic Protein Health Holocaust survivor Impaired cognition Incidence Individual Inhalation Life Cycle Stages Light Link Liquid substance Longitudinal Studies Measures Memory Monitor Nerve Degeneration Neurobehavioral Manifestations Neurotoxins Particulate Matter Pathologic Phosphorylation Pilot Projects Plasma Population Post-Traumatic Stress Disorders Prevention Questionnaires Recovery Reporting Research Research Infrastructure Research Personnel Risk Risk Factors Sampling Severities Smoke Societies Stress Stressful Event Symptoms Tauopathies Thallium Time Trauma United States National Institutes of Health Urine Veterans Woman Work biological adaptation to stress blood-based biomarker care costs cognitive function cognitive performance cognitive reserve cohort comorbidity cost cost estimate design experience high risk lifetime risk men middle age mild cognitive impairment nanoparticulate nervous system disorder neurofilament neuroinflammation neuropathology neurotoxic novel operation physical symptom pre-clinical resilience factor response senescence stressor tau Proteins tau-1 β-amyloid burden

项目摘要

Abstract Alzheimer’s disease (AD) caused more than 110,000 deaths in 2017 making it the sixth most common cause of death. With an estimated lifetime risk of 40% in the U.S. population and an estimated cost of care exceeding $200 billion, ADRD is burdensome for individuals and their families, and costly to society. While work is increasingly determining risk and resilience factors for ADRD, little is known about causes of preclinical AD. Life course researchers have posited that a lifetime of stressors can accumulate to cause increased incidence of symptoms consistent with preclinical AD including changes to memory and early stages of cognitive impairment. In creating the first and only cognitive monitoring study of World Trade Center responders (R01 AG049953; PI, Clouston), we posited that chronic posttraumatic stress disorder (PTSD), a relatively common disorder characterized by intrusive memories of past trauma accompanied by a heightened stress response, might help to provide a unique mechanism linking lifetime stressors with later onset of cognitive decline reminiscent of ADRD. Those data sought to examine the extent to which childhood exposures, midlife exposures, genetic differences, and later-life changes in health would help to explain cognitive symptoms of preclinical AD in World Trade Center responders. While we now understand that PTSD predicts increased risk of cognitive and physical symptoms consistent with preclinical AD, the mechanisms of action for this association remain opaque. In a recent pilot study, we found that WTC responders have increased plasma neurofilament-light and plasma tau (which was associated with memory in this sample), and also identified a strong association between PTSD and changes to plasma amyloid-b burden. We now posit that PTSD may either cause an Alzheimer’s pathological cascade with one result being cognitive dysfunction in domains of fluid cognition including memory. This study seeks to examine, using longitudinal data, the extent to which PTSD might trigger an AD neuropathological cascade. However, since responders are very young to be experiencing ADRD, we additionally hypothesize that PSTD may reduce cognitive reserve thereby amplifying the effects of extant neuropathology. Finally, we propose an alternative hypothesis stating that inhaled nanoparticulate matter exposures, which some responders reported while at the WTC may have increased the burden of a known neurotoxin with one result being increased risk of neuropathological changes including increased tauopathy. !

抽象的阿尔茨海默氏病（AD）在2017年造成11万多人死亡，这是第六大最常见原因死亡。美国人口估计有40％的终身风险，估计的护理费用超过 2000亿美元的ADRD对个人及其家人来说是繁殖的，对社会来说是昂贵的。虽然工作是越来越多地确定了ADRD的风险和弹性因素，对临床前AD的原因知之甚少。生命课程研究人员认为，一生的压力源会累积以引起发病率的增加症状与临床前广告一致的症状，包括对记忆的变化和认知早期阶段损害。在创建世界贸易中心响应者的第一个也是唯一的认知监测研究时（R01 AG049953; PI，Cloudon），我们保证了慢性创伤后应激障碍（PTSD），一种相对较长的常见疾病的特征是过去创伤的侵入性记忆，并伴有增强压力反应可能有助于提供一种独特的机制，将终身压力与以后的发作联系起来认知能力下降，让人联想到ADRD。那些数据感以检查童年的程度暴露，中年暴露，遗传差异和后来的健康变化将有助于解释世界贸易中心响应者临床前广告的认知症状。虽然我们现在了解PTSD 预测与临床前AD一致的认知和身体症状的风险增加了该协会的行动仍然不透明。在最近的一项试点研究中，我们发现WTC响应者有增加了血浆神经丝光和血浆TAU（与该样品中的记忆有关），并且还确定了PTSD与血浆淀粉样蛋白B负担的变化之间的密切关联。我们现在定位 PTSD可能会引起阿尔茨海默氏症的病理级联，其中一个是认知功能障碍流体认知的域，包括记忆。本研究旨在使用纵向数据检查 PTSD可能会引发AD神经病理级联反应。但是，由于响应者很小要经历ADRD，我们还假设PSTD可能会减少认知储备扩大额外神经病理学的影响。最后，我们提出了一个替代假设，指出继承的纳米含量暴露，一些响应者在WTC时报告了这一点增加了已知神经毒素的燃烧，其中一种是增加神经病理变化的风险包括增加的tauopathy。呢

项目成果

期刊论文数量（49）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

World Trade Center Site Exposure Duration Is Associated with Hippocampal and Cerebral White Matter Neuroinflammation.

DOI：
10.1007/s12035-022-03059-z
发表时间：
2023-01
期刊：
MOLECULAR NEUROBIOLOGY
影响因子：
5.1
作者：
Huang, Chuan;Kritikos, Minos;Sosa, Mario Serrano;Hagan, Thomas;Domkan, Alan;Meliker, Jaymie;Pellecchia, Alison C.;Santiago-Michels, Stephanie;Carr, Melissa A.;Kotov, Roman;Horton, Megan;Gandy, Sam;Sano, Mary;Bromet, Evelyn J.;Lucchini, Roberto G.;Clouston, Sean A. P.;Luft, Benjamin J.
通讯作者：
Luft, Benjamin J.

Chronic Posttraumatic Stress Disorder and Comorbid Cognitive and Physical Impairments in World Trade Center Responders.

DOI：
10.1002/jts.22631
发表时间：
2021-06
期刊：
Journal of traumatic stress
影响因子：
3.3
作者：
Diminich ED;Clouston SAP;Kranidis A;Kritikos M;Kotov R;Kuan P;Carr M;Bromet EJ;Luft BJ
通讯作者：
Luft BJ

Functional changes in neural mechanisms underlying post-traumatic stress disorder in World Trade Center responders.

DOI：
10.1038/s41398-023-02526-y
发表时间：
2023-07-11
期刊：
TRANSLATIONAL PSYCHIATRY
影响因子：
6.8
作者：
Invernizzi, Azzurra;Rechtman, Elza;Curtin, Paul;Papazaharias, Demetrios M.;Jalees, Maryam;Pellecchia, Alison C.;Santiago-Michels, Stephanie;Bromet, Evelyn J.;Lucchini, Roberto G.;Luft, Benjamin J.;Clouston, Sean A.;Tang, Cheuk Y.;Horton, Megan K.
通讯作者：
Horton, Megan K.

"Association of Severity of Posttraumatic Stress Disorder With Inflammation: Using Total White Blood Cell Count as a Marker".