Transforming Research and Clinical Knowledge in Older Veterans with Acute Traumatic Brain Injury (TRACK-VA)

改变患有急性创伤性脑损伤的老年退伍军人的研究和临床知识 (TRACK-VA)

• 批准号: 10549742
• 负责人: Pratik Mukherjee
• 金额: --
• 依托单位: VETERANS AFFAIRS MED CTR SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10549742
• 关键词: Accident and Emergency department; Acute; Address; Adult; Age; Aging; Amyloid beta-42; Amyloid beta-Protein; Area; Biologic Characteristic; Biological; Biological Markers; Blood; Chemical Exposure; Clinical; Clinical Sciences; Clinical Trials; Clinical assessments; Cognitive; Common Data Element; Data; Dementia; Development; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Elderly; Enrollment; Epidemic; Exclusion; Functional Magnetic Resonance Imaging; Funding; Glial Fibrillary Acidic Protein; Health; Healthcare; Hospitals; Image; Impaired cognition; Incidence; Injury; Knowledge; Magnetic Resonance Imaging; Medical; Military Personnel; Monitor; Morbidity - disease rate; National Institute of Neurological Disorders and Stroke; Neurites; Older Population; Orthopedics; Outcome; Patients; Phenotype; Population; Post-Traumatic Stress Disorders; Predisposition; Prognosis; Prospective Studies; Prospective cohort; Prospective, cohort study; Proteomics; Protocols documentation; Recovery of Function; Research; Research Infrastructure; Research Priority; Residual state; Rest; Risk Factors; Services; Site; Specificity; TBI Patients; Trauma; Traumatic Brain Injury; United States National Institutes of Health; Veterans; Veterans Health Administration; active duty; age related; blast exposure; brain magnetic resonance imaging; care burden; clinical phenotype; cohort; cost; density; disability; effective intervention; endophenotype; evidence based guidelines; falls; high risk; improved outcome; medical attention; mild traumatic brain injury; military veteran; mortality; multidisciplinary; neuroimaging; neuroimaging marker; precision medicine; public health emergency; research and development; service member; substance use; tau-1; timeline; trauma centers

Acute traumatic brain injury (TBI) in older veterans is an under-recognized public health emergency for Veterans Health Administration (VHA). The highest and fastest rising incidence of TBI in the U.S. is in older adults, mostly due to ground-level falls. Compared with younger patients, older adults with TBI have higher mortality, lower rates of functional recovery, and may be at especially high risk for post-TBI dementia. Details of clinical and biological characteristics of older Veterans with acute TBI are incomplete, and insufficient to implement evidence-based practice guidelines or plan clinical trials. However, pre-existing TBI, medical/psychiatric conditions, and substance use – common in older Veterans – are emerging risk factors for sustaining TBI and for worse outcomes after TBI. There is an urgent need to comprehensively characterize acute TBI in older Veterans presenting to VA hospitals to inform effective interventions to optimize outcomes. Barriers to progress are: 1) Older adults, especially older Veterans, are underrepresented in acute TBI research. The 18-site NINDS-funded Transforming Research and Clinical Knowledge in TBI study (TRACK- TBI; U01NS086090) had no VA sites and, per protocol, excluded older adults with pre-existing conditions; (2) Emerging TBI blood-based and neuroimaging biomarkers have not been validated in older Veterans, many with pre-existing conditions and military relevant exposures that may reduce accuracy. To begin to address age-related barriers to progress, we received funding from NIH for the Transforming Research and Clinical Knowledge in Geriatric TBI (TRACK-GERI; R01 NS110944 2019-2024) study, a 5-year 2-site TRACK-TBI Network prospective cohort of acute geriatric TBI in patients presenting to Level 1 trauma centers. However, this study will not capture patients who present to VAs or non-trauma center Emergency Departments (ED). Thus, TRACK-GERI will not elucidate the unique features of geriatric TBI in Veterans presenting with mostly mild TBI to VA EDs. To fill this gap, we propose to leverage the existing TRACK-TBI Network data and expertise of our exceptional multi-disciplinary team at SFVA/UCSF to achieve these scientific aims: Aim 1: Characterize baseline and 12-mo longitudinal clinical features using TBI Common Data Elements (CDEs) among Veterans age ≥65y enrolled in the TRACK-TBI and TRACK-GERI studies with acute TBI. We will analyze existing data collected at TRACK-TBI’s 18 non-VA Level 1 trauma centers and explore comparisons to civilians (existing geriatric cohort data consists of N>60 Veterans, N>250 civilians).Aim 2: Assemble a new prospective cohort of Veterans age ≥65y presenting to SFVA ED ≤72h after TBI who received CT (“TRACK- VA”) and deeply phenotype clinical and biological features over 12-months using TBI CDEs. Enroll 70 TBI patient/study-partner dyads and 30 matched ED controls (with medical/orthopedic conditions discharged from the ED), perform baseline clinical assessments (pre-injury health, MREs), blood draws (for APOE, proteomic analysis), brain MRI, and assess longitudinal outcomes at 2wk, 3mo, 6mo, and 12mo post-injury. Aim 3: Characterize neuroimaging features of acute geriatric TBI in Veterans using TBI CDEs and quantitative structural and functional MRI. Obtain structural (T1, T2, susceptibility weighted imaging, multi-shell diffusion imaging, diffusion tensor imaging, neurite orientation dispersion and density imaging) and resting-state functional MRI at 2-wks, 6-mo, and 12-mo post-injury in a sub-set of the TRACK-VA cohort (N=50 TBI; N=25 controls). Characterize acute intracranial trauma on 2-week MRI and characterize longitudinal structural and functional changes. Aim 4: Determine accuracy of blood-based GFAP, P-tau, Abeta, and NFL for TBI diagnosis, prognosis of outcome, and disease-monitoring in older Veterans. We will obtain blood at £72h, 6mo, and 12mo post-injury. This project will comprehensively characterize baseline and longitudinal endophenotypes of an intentionally heterogeneous, “real-world,” population of older Veterans presenting with acute TBI. Findings will inform development of effective interventions to optimize outcomes.

老年退伍军人的急性创伤性脑损伤（TBI）是公众不足的公共卫生紧急情况 退伍军人卫生管理局（VHA）。美国TBI的最高和最快的上升事件是年龄较大的 成年人，主要是由于地面瀑布。与年轻患者相比，患有TBI的老年人具有更高的 死亡率，功能恢复率较低，可能是TBI后痴呆症的高风险。细节 急性TBI老年退伍军人的临床和生物学特征是不完整的，不足 实施循证实践指南或计划临床试验。但是，先前存在的tbi， 医学/精神病疾病和使用物质（在老年退伍军人中常见）是新兴的风险因素 维持TBI并在TBI之后的情况下取得更严重的结果。迫切需要全面描述 向VA医院展示的老年退伍军人的急性TBI，以告知有效的干预措施以优化结果。 进步的障碍是：1）急性TBI的老年人，尤其是老年退伍军人的人数不足 研究。 TBI研究中的18个地点Ninds资助的转型研究和临床知识（Track- tbi; U01NS086090）没有VA地点，并且根据规程排除了具有先前情况的老年人； （2） 新兴的TBI血液和神经影像学生物标志物尚未在老年退伍军人中得到验证，许多 既有先前存在的条件和军事相关暴露，可以降低准确性。开始解决 与年龄相关的进步障碍，我们从NIH获得了转型研究和临床的资金 老年TBI的知识（Track-Geri; R01 NS110944 2019-2024）研究，一项5年2年的2个轨道TBI 急性老年TBI的网络前瞻性队列在1级创伤中心的患者中。然而， 这项研究不会捕获出现在VAS或非创伤中心急诊科（ED）的患者。 那就是Track-Geri不会阐明老年TBI在退伍军人中的独特特征 轻度TBI到VA eds。为了填补这一空白，我们建议利用现有的轨道-TBI网络数据和 我们在SFVA/UCSF的卓越多学科团队的专业知识，以实现这些科学目的：目标1： 使用TBI通用数据元素（CDE）表征基线和12个MO纵向临床特征 在急性TBI的TRACK-TBI和Track-GERI研究中，≥65岁的退伍军人中≥65岁。我们将 分析在Track-TBI的18个非VA 1级创伤中心收集的现有数据，并探索与 平民（现有的老年人群数据由N> 60名退伍军人组成，N> 250平民）.AIM 2：组装新的 接受CT的TBI之后，向SFVA ED≤72H的退伍军人的预期队列≥65岁（track- VA”）和使用TBI CDE的12个月以上的表型临床和生物学特征。注册70 TBI 患者/研究合作伙伴二元组和30个匹配的ED对照（医疗/骨科条件从 ED），进行基线临床评估（受伤前健康，MRES），血液抽血（对于APOE，蛋白质组学 分析），2WK，3MO，6MO和12MO后伤害后的脑部MRI和评估纵向结局。目标3： 使用TBI CDE和定量表征退伍军人中急性老年TBI的神经影像学特征 结构和功能性MRI。获得结构（T1，T2，敏感性加权成像，多壳扩散 成像，扩散张量成像，神经元化分散和密度成像）和静止状态 在2周，6-MO和12-MO后的功能性MRI，在Track-Va队列的子集中受伤（n = 50 tbi; n = 25） 控件）。表征2周MRI上急性颅内创伤，并表征纵向结构和 功能变化。目标4：确定基于血液的GFAP，P-TAU，ABETA和NFL的准确性 老年退伍军人的诊断，预后的预后和疾病监控。我们将以72小时（6mo）的价格获得血液 和12mo后伤害。该项目将全面地表征基线和纵向 有意异构的“现实世界”的内表型，呈现的老年退伍军人 急性TBI。调查结果将为您开发有效的干预措施，以优化结果。