Transforming Research And Clinical Knowledge in Geriatric Traumatic Brain Injury (TRACK-GERI)

项目概要/摘要 每年约有 280 万美国人因创伤性脑损伤 (TBI) 寻求医疗救助，导致 估计每年的成本超过 750 亿美元。老年人的 TBI 上升率最高且最快 其他年龄组，2013 年，每 50 名 75 岁以上成年人中就有 1 人因 TBI 寻求医疗救助。 患有 TBI 的老年人 死亡率更高、恢复更慢、结果更差，并且可能面临特别高的 TBI 后风险 失智。缺乏基于证据的管理指南，没有为患者和家属提供的工具 对预后的可靠估计，以及经过验证的治疗方法很少。进展受到以下因素的限制： 1. 系统性 大多数先前的前瞻性 TBI 研究将老年残疾患者排除在外，以及 2. 缺乏适合年龄的 TBI 研究工具。总体目标是启动一项 2 中心前瞻性老年 TBI 队列研究，该研究将直接 通过将最先进的老年研究方法应用于 TBI 领域来解决这些障碍，以改善 老年患者在 TBI 研究中的代表性，并开发一种测量年龄的新方法 适当的 TBI 预测因素、结果、血液生物标志物和神经病理学。该方法基于 2 基本概念： 1. 老年 TBI 不同于年轻患者的 TBI，需要有目标年龄 适当的方法。 2. 基线健康状况 – 包括合并症/多重用药、身体虚弱、 功能状态和大脑结构——被认为是老年病学领域结果的关键预测因素，但 TBI 研究中没有系统地测量。中心假设是受伤前的健康状况将 老年 TBI 的异质性极强，将成为该人群结果的关键预测因素。安 由 TBI 和衰老研究领域的杰出专家组成的团队将实现以下目标： 目标 1：组建一个前瞻性的团队 年龄≥65岁、在TBI后≤72小时到急诊科接受CT检查的患者队列。报名 270 名 TBI 患者/研究伙伴二人组和 90 名对照；进行基线评估和抽血，以及 评估 2 周、3 个月、6 个月（主要终点）和 12 个月的纵向结果；提供大脑登记 捐赠计划。目标 2：开发并验证优化的老年 TBI 预测因子和结果评估： 2a：系统测量载脂蛋白 E 等位基因和损伤前合并症/多药治疗、身体虚弱、 通过使用经过验证的老年病学对患者和研究合作伙伴进行详细访谈，了解多领域功能状态 仪器并评估这些预测因素与 TBI 后结果的关联。 2b：描述自然历史 使用经过验证的 TBI 和老年结果来评估老年 TBI，然后使用数据驱动的分析来确定 对这一人群进行纵向结果评估的最简约的一套措施。 2c（探索性）： 测量受伤前的大脑结构（基线 CT 上显示的未受伤大脑的萎缩/白质疾病） 并探讨与 TBI 后结果的关联。目标 3：确定适合年龄的诊断和预后 基于血液的生物标志物。这项工作将直接为大规模适合年龄的老年 TBI 的设计提供信息 迫切需要进行临床试验来改善这一弱势群体的护理和结果。

PROJECT SUMMARY / ABSTRACT Some 2.8 million Americans seek medical attention for traumatic brain injury (TBI) annually, resulting in estimated annual costs of over $75 billion. Older adults have the highest and fastest rising rate of TBI of any other age-group, with 1 in 50 adults age ≥75y seeking medical attention for TBI in 2013. Older adults with TBI experience higher mortality, slower recovery, worse outcomes, and may be at especially high risk for post-TBI dementia. There are few evidence-based guidelines for management, no tools to provide patients and families with reliable estimates of prognosis, and few proven treatments. Progress has been limited by: 1. systematic exclusion of older disabled patients from most prior prospective TBI studies, and 2. lack of age-appropriate TBI research tools. The overall objective is to launch a 2-site prospective geriatric TBI cohort study that will directly address these barriers by applying state-of-the-art geriatric research methods to the field of TBI to improve representation of older patients in TBI research, and to develop a novel approach to measuring age- appropriate TBI predictors, outcomes, blood-based biomarkers, and neuropathology. The approach rests on 2 foundational concepts: 1. Geriatric TBI is different from TBI in younger patients and will require a targeted age- appropriate approach. 2. Baseline health status – including comorbidities/polypharmacy, physical frailty, functional status, and brain structure – is recognized as a key predictor of outcome in the field of geriatrics but is not systematically measured in TBI research. The central hypothesis is that pre-injury health will be extremely heterogeneous in geriatric TBI and will be a key predictor of outcome in this population. An outstanding team of experts in TBI and aging research will achieve these Aims: Aim 1: Assemble a prospective cohort of patients age ≥65y presenting to the Emergency Department ≤72h after TBI who underwent CT. Enroll 270 TBI patient/study-partner dyads and 90 controls; perform baseline assessments and blood draws, and assess longitudinal outcomes at 2wk, 3mo, 6mo (primary endpoint) and 12mo; offer enrollment in a brain donation program. Aim 2: Develop and validate optimized geriatric TBI predictor and outcome assessments: 2a: Systematically measure apolipoprotein E allele and pre-injury comorbidities/polypharmacy, physical frailty, and multi-domain functional status via detailed patient and study partner interviews using validated geriatric instruments and assess association of these predictors with outcome after TBI. 2b: Describe the natural history of geriatric TBI using validated TBI and geriatric outcomes and then use data-driven analytics to identify the most parsimonious set of measures for longitudinal outcome assessment in this population. 2c (exploratory): Measure pre-injury brain structure (atrophy/white matter disease of uninjured brain visualized on baseline CT) and explore association with outcome after TBI. Aim 3: Identify age-appropriate diagnostic and prognostic blood-based biomarkers. This work will directly inform design of large-scale age-appropriate geriatric TBI clinical trials that are urgently needed to improve care and outcomes in this vulnerable population.