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）是一种未被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 发病率最高且上升最快的是老年人 成年人，主要是由于地面跌倒造成的。与年轻患者相比，患有 TBI 的老年人的患病率更高 死亡率、功能恢复率较低，并且患 TBI 后痴呆的风险特别高。详情 患有急性 TBI 的老年退伍军人的临床和生物学特征的研究不完整，不足以 实施循证实践指南或计划临床试验。然而，已有的 TBI， 医疗/精神疾病和药物滥用（在老年退伍军人中很常见）是新出现的危险因素 持续 TBI 以及 TBI 后更糟糕的结果。迫切需要全面表征 老年退伍军人的急性创伤性脑损伤到退伍军人管理局医院就诊，以提供有效的干预措施以优化结果。 进展的障碍是： 1) 老年人，尤其是老年退伍军人，在急性 TBI 中所占比例不足 研究。 NINDS 资助的 18 个中心的 TBI 研究转化研究和临床知识 (TRACK- 创伤性脑损伤； U01NS086090）没有 VA 站点，并且根据方案，排除了患有既往疾病的老年人； (2) 新兴 TBI 血液和神经影像生物标志物尚未在老年退伍军人中得到验证，许多 已有条件和军事相关暴露可能会降低准确性。开始解决 由于年龄相关的进展障碍，我们获得了 NIH 的资助，用于转化研究和临床 老年 TBI 知识（TRACK-GERI；R01 NS110944 2019-2024）研究，一项为期 5 年的 2 点 TRACK-TBI 就诊于 1 级创伤中心的患者的急性老年 TBI 网络前瞻性队列。然而， 本研究不会收集到 VA 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 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 网络数据和 SFVA/UCSF 杰出的多学科团队的专业知识来实现这些科学目标： 目标 1： 使用 TBI 通用数据元素 (CDE) 描述基线和 12 个月纵向临床特征 参加 TRACK-TBI 和 TRACK-GERI 研究的患有急性 TBI 的年龄≥65 岁的退伍军人。我们会 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（现有老年队列数据包括 N>60 名退伍军人、N>250 名平民）。目标 2：组建新的 年龄≥65 岁、在 TBI 后 72 小时内就诊于 SFVA 且接受 CT 治疗的退伍军人前瞻性队列（“TRACK- VA”），并使用 TBI CDE 在 12 个月内深入分析临床和生物学特征。注册 70 TBI 患者/研究伙伴二人组和 30 名匹配的 ED 对照（具有从医院出院的医疗/骨科疾病） ED），进行基线临床评估（受伤前健康状况，MRE），抽血（APOE，蛋白质组学） 分析）、脑 MRI，并评估受伤后 2 周、3 个月、6 个月和 12 个月的纵向结果。目标 3： 使用 TBI CDE 和定量描述退伍军人急性老年 TBI 的神经影像学特征 结构和功能 MRI。获得结构（T1、T2、磁化率加权成像、多壳扩散 成像、扩散张量成像、神经突方向分散和密度成像）和静息态 TRACK-VA 队列子集损伤后 2 周、6 个月和 12 个月的功能性 MRI（N=50 TBI；N=25） 控制）。通过 2 周 MRI 表征急性颅内创伤，并表征纵向结构和特征 功能变化。目标 4：确定基于血液的 GFAP、P-tau、Abeta 和 NFL 对于 TBI 的准确性 老年退伍军人的诊断、结果预后和疾病监测。我们将在 72 英镑小时、6 个月时采血， 以及受伤后12个月。该项目将全面描述基线和纵向特征 故意异质的“现实世界”老年退伍军人群体的内表型 急性脑外伤。研究结果将为制定有效的干预措施以优化结果提供信息。

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.