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

老年退伍军人的急性创伤性脑损伤（TBI）是一种未得到充分认识的公共卫生紧急情况， 退伍军人健康管理局（VHA）。在美国，TBI发病率最高和上升最快的是老年人。 成年人，主要是由于地面福尔斯。与年轻患者相比，患有TBI的老年人 死亡率，功能恢复率较低，并且可能处于TBI后痴呆的特别高的风险中。细节 患有急性TBI的老年退伍军人的临床和生物学特征是不完整的，不足以 实施循证实践指南或计划临床试验。然而，预先存在的TBI， 医疗/精神疾病和物质使用-在老年退伍军人中很常见-是新出现的风险因素， 持续TBI和TBI后更差的结果。迫切需要全面描述 老年退伍军人急性TBI到VA医院提供有效的干预措施，以优化结果。 进展的障碍是：1）老年人，特别是老年退伍军人，在急性TBI中代表性不足 research. NINDS资助的18个研究中心TBI研究中的转化研究和临床知识（TRACK- TBI; U 01 NS 086090）没有VA部位，并且根据方案，排除了既存疾病的老年人;（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 与预先存在的条件和军事相关的风险，可能会降低准确性。开始处理 与年龄有关的进展障碍，我们获得了NIH的资助，用于转化研究和临床研究。 老年TBI知识（TRACK-GERI; R 01 NS 110944 2019-2024）研究，一项为期5年的2中心TRACK-TBI 1级创伤中心急性老年TBI患者的网络前瞻性队列研究然而，在这方面， 本研究将不收集到VA或非创伤中心急诊科（艾德）就诊的患者。 因此，TRACK-GERI不会阐明退伍军人中老年TBI的独特特征， 轻度TBI至VA ED。为了填补这一空白，我们建议利用现有的TRACK-TBI网络数据， 我们在SFVA/UCSF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通用数据元素（CDE）表征基线和12个月纵向临床特征 在入组TRACK-TBI和TRACK-GERI研究的年龄≥ 65岁的急性TBI退伍军人中。我们将 分析TRACK-TBI的18个非VA 1级创伤中心收集的现有数据，并探索与 目标2：组建一个新的老年组群（现有老年组群数据包括N>60名退伍军人，N>250名平民）。 年龄≥ 65岁的退伍军人在TBI后≤ 72小时内接受SFVA艾德并接受CT的前瞻性队列（“TRACK- VA”）和使用TBI CDE在12个月内的深度表型临床和生物学特征。入组70例TBI 患者/研究伙伴二人组和30名匹配的艾德对照组（医疗/整形外科条件从 艾德），进行基线临床评估（损伤前健康，MRE），抽血（用于APOE，蛋白质组学 分析），脑MRI，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： 使用TBI CDE和定量分析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MRI。获得结构（T1、T2、磁敏感加权成像、多壳层扩散 成像、扩散张量成像、神经突取向分散和密度成像）和静息状态 在TRACK-VA队列的一个子集中，在损伤后2周、6个月和12个月时进行功能性MRI（N=50例TBI; N=25例 对照）。在2周MRI上表征急性颅内创伤，并表征纵向结构和 功能变化。目的4：确定基于血液的GFAP、P-tau、Abeta和NFL用于TBI的准确性 诊断，预后的结果，并在老年退伍军人疾病监测。我们将在72小时6个月获得血液， 伤后12个月。该项目将全面描述基线和纵向 一个故意异质性的，“真实世界”的老年退伍军人人群的内在表型， 急性TBI。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.