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

项目摘要/摘要 每年约有280万美国人因创伤性脑损伤(TBI)寻求医疗护理，导致 估计每年的成本超过750亿美元。老年人的脑损伤上升速度最快、最快。 其他年龄段，≥75岁的成年人中每50人中就有1人在2013年因脑外伤寻求医疗救治。老年脑外伤患者 经历更高的死亡率，更慢的恢复，更差的结果，并可能处于特别高的脑外伤后风险 痴呆症。几乎没有循证的管理指南，没有工具为患者和家属提供 对预后有可靠的估计，几乎没有经过验证的治疗方法。进展受到以下因素的限制：1.系统性 将老年残疾患者排除在大多数先前的前瞻性脑损伤研究之外，以及2.缺乏与年龄相适应的脑损伤 研究工具。总体目标是启动一项两个地点的前瞻性老年脑损伤队列研究，将直接 通过将最先进的老年学研究方法应用于脑外伤领域来解决这些障碍，以改善 老年患者在脑损伤研究中的代表性，并开发一种新的方法来测量年龄- 合适的脑损伤预测因素、结果、基于血液的生物标记物和神经病理学。该方法依赖于2 基本概念：1.老年性脑外伤不同于年轻患者的脑外伤，需要有针对性的年龄-- 适当的方法。2.基线健康状况--包括合并症/多药、身体虚弱、 功能状态和大脑结构-在老年病学领域被认为是预后的关键预测因素，但 在TBI研究中没有系统地测量。核心假设是受伤前的健康状况将是 老年性脑外伤的异质性很强，这将是这一人群预后的关键预测因素。一个 TBI和老龄化研究领域的优秀专家团队将实现这些目标：目标1：集合未来的 年龄为≥65岁的患者在颅脑损伤后72小时到急诊科≤接受CT检查。报名 270名脑损伤患者/研究伙伴二人组和90名对照；执行基线评估和抽血，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；提供大脑注册 捐赠计划。目标2：开发和验证优化的老年脑损伤预测指标和结果评估： 系统地检测载脂蛋白E等位基因和损伤前的合并症/多药、身体虚弱、 通过使用经过验证的老年患者和研究伙伴的详细访谈，了解多领域的功能状态 评估这些预测因素与脑外伤后预后的关系。2B：描述自然历史 使用有效的TBI和老年结果来评估老年脑损伤，然后使用数据驱动的分析来确定 在这一人群中进行纵向结果评估的最简明的一套措施。2C(探索性)： 测量损伤前的脑结构(在基线CT上显示未损伤的脑萎缩/白质疾病) 并探讨其与颅脑损伤后预后的关系。目标3：确定适合年龄的诊断和预后 基于血液的生物标记物。这项工作将直接为大规模适龄老年脑外伤的设计提供参考 迫切需要进行临床试验，以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.