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

• 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
• 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' s Disease; Alzheimer' 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

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110,000多人死亡，这是第六个最常见的原因 死亡。 2000亿美元的ADRD对个人及其家人来说是繁重的，在工作时对社会来说是昂贵的 对ADRD的风险和弹性因素越来越多，关于临床前AD的原因知之甚少。 生命课程研究人员认为，一生的压力源可以累积以引起增加 与临床前广告一致的症状，将记忆的变化和认知的早期阶段一致 障碍。 （R01 AG049953; PI，Clouston），我们认为慢性创伤后应激障碍（PTSD）是一个相对较高的 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。 暴露，中年暴露，遗传差异和后来的健康变化将有助于解释 世界贸易中心反应中临床前广告的认知症状。 预测增加了与临床前AD一致的认知和身体症状的风险 该关联的作用仍然是不透明的。 增加了血浆神经丝光和血浆TAU（该样品中的记忆与记忆有关）， 还确定了PTSD与等离子淀粉样蛋白B负担之间的关联 PTSD可能会引起阿尔茨海默氏症的病理级联反应，结果是认知功能障碍 包括记忆在内的流体认知领域。 PTSD可能会触发AD神经病理学的级联。 要经历ADRD，我们还假设假设可以减少Bybybyby的认知储备 扩大现有神经病理学的影响。 吸入的纳米核心物质暴露，一些响应者在WTC时报告了这一点 增加了已知神经毒素的负担，导致神经性疾病的风险不断变化 包含提高的tauopathy。 呢

项目成果

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".

• DOI: 10.1177/2470547019877651
• 发表时间: 2019-01-01
• 期刊: Chronic stress (Thousand Oaks, Calif.)
• 作者: Koraishy, Farrukh M;Salas, Joanne;Scherrer, Jeffrey F
• 通讯作者: Scherrer, Jeffrey F

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

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.

Acute versus Chronic Exposures to Inhaled Particulate Matter and Neurocognitive Dysfunction: Pathways to Alzheimer's Disease or a Related Dementia.

• DOI: 10.3233/jad-200679
• 发表时间: 2020
• 期刊: Journal of Alzheimer's disease : JAD
• 作者: Kritikos M;Gandy SE;Meliker JR;Luft BJ;Clouston SAP
• 通讯作者: Clouston SAP