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

老年退伍军人急性创伤性脑损伤是一种未被充分认识的突发公共卫生事件 退伍军人健康管理局(VHA)。在美国，脑外伤发病率最高、上升最快的是老年人 成人，主要是由于地面坠落。与年轻患者相比，老年脑外伤患者的发病率更高 死亡率，较低的功能恢复率，并可能是脑外伤后痴呆的特别高风险。详细信息 老年退伍军人急性颅脑损伤的临床和生物学特征不完整，不足以 实施循证实践指南或计划临床试验。然而，先前存在的TBI， 医疗/精神状况和物质使用--在老年退伍军人中很常见--是新出现的危险因素 持续的脑损伤和脑损伤后更糟糕的结果。迫切需要全面地描述 老年退伍军人中的急性脑损伤向退伍军人医院提出有效的干预措施，以优化结果。 取得进展的障碍是：1)老年人，特别是老年退伍军人，在急性脑外伤中的代表性不足 研究。由NINDS资助的18个站点的转化研究和临床知识在脑损伤研究(Track- TbI；U01NS086090)没有VA部位，根据协议，排除了有既往疾病的老年人；(2) 新出现的基于血液和神经成像的脑损伤生物标记物尚未在许多老年退伍军人中得到验证 预先存在的疾病和与军事相关的暴露可能会降低准确性。开始着手解决 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 老年脑外伤的知识(TRACK-GERI；R01 NS110944 2019-2024)研究，为期5年的2个部位的脑损伤 出现在1级创伤中心的老年急性脑外伤患者的网络前瞻性队列。然而， 这项研究不包括到VAS或非创伤中心急诊科(ED)就诊的患者。 因此，Track-GERI不会阐明退伍军人中老年脑外伤的独特特征，主要表现为 轻度创伤性脑损伤至VA急救。为了填补这一空白，我们建议利用现有的Track-TBI网络数据和 我们在旧金山大学/加州大学旧金山分校卓越的多学科团队的专业知识，以实现这些科学目标：目标1： 使用TBI公共数据元素(CDE)描述基线和12个月纵向临床特征 在参加Track-≥和Track-GERI研究的65岁退伍军人中，他们患有急性脑外伤。我们会 分析在Track-TBI的18个非退伍军人事务部1级创伤中心收集的现有数据，并探索与 平民(现有的老年队列数据包括60名退伍军人，250名平民)。目标2：组建一个新的 年龄为≥65岁的退伍军人在脑外伤后72小时到SFVA Ed≤接受CT检查的预期队列(“Track- Va“)，并在12个月内使用脑损伤CDE进行表型、临床和生物学特征的深入研究。注册70个TBI 患者/研究伙伴二人组和30名匹配的ED对照组(有医疗/矫形条件的患者从 ED)，执行基线临床评估(受伤前健康，MRE)、抽血(APOE，蛋白质组 分析)，并评估损伤后2周、3个月、6个月和12个月的纵向结果。目标3： 退伍军人急性老年性颅脑损伤的脑CDE和定量研究 结构和功能磁共振成像。获得结构(T1、T2、磁化率加权成像、多壳层扩散 成像、扩散张量成像、轴突定向弥散和密度成像)和静息状态 Track-VA组(N=50个TBI；N=25个)损伤后2周、6个月和12个月的功能磁共振成像 控制)。在2周的MRI上描述急性颅脑损伤的特征，并描述纵向结构和 功能变化。目的4：确定基于血液的GFAP、P-tau、Abeta和NFL对脑外伤的准确性 老年退伍军人的诊断、预后和疾病监测。我们将在国标72小时，6个月， 伤后12个月。该项目将全面描述基线和纵向特征 特意异质的“真实世界”老年退伍军人群体的内表型 急性颅脑损伤。调查结果将为制定有效的干预措施提供信息，以优化结果。

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.