Comprehensive Investigation of the Clinical Course of Traumatic Brain Injury

描述（由申请人提供）：创伤性脑损伤（TBI）是美国的一个主要公共卫生问题，目前TBI在美国的患病率是前所未有的。TBI患者经历了不同的早期恢复模式和长期临床结果，一些TBI幸存者随着年龄的增长经历了加速的认知和健康下降。人们对预测不同结果轨迹的因素知之甚少。一般而言，与老年人认知和健康下降相关的因素的程度（例如，缺乏身体活动， 医学并发症）是否适用于有TBI病史的老年人尚不清楚。许多现有的研究面临着方法学上的挑战，限制了它们在评估认知和健康结果方面的有用性，例如样本量小，随访有限，使用不精确的功能测量，以及应用传统的回归方法，其假设通常不符合纵向临床研究。我们目前对TBI结果的了解受到这些局限性的限制。心理测量学和统计建模的最新方法学发展可以应用于现有的数据集，如这里所提出的，以显着推进对TBI结果的理解，以及随着时间的推移影响这些结果的因素。拟议的研究和职业发展计划将首先评估和解释常用的TBI结果测量中的测量不精确性，然后使用非常适合此目的的先进统计方法评估TBI患者认知和健康结果的时间变化轨迹。 本申请中概述的研究和职业发展计划包括四个互补目标，将在奖励期间实施。目标1的目的是发展熟练的应用先进的心理测量方法，以评估和调整测量误差和偏见，在常用的创伤性脑损伤评估工具。目标2是掌握应用复杂的统计方法，这些方法能够评估影响TBI结果的因素之间的纵向关系，并将个体临床轨迹与TBI的死后神经病理学特征联系起来。目标3涉及建立广泛的神经病理学，神经影像学和遗传学的相关学科的流畅性，这是必要的跨学科TBI研究。目标4：确保独立研究经费。 与K01奖项相关的研究结果将促进对与TBI后临床结果异质性相关的潜在可改变因素的了解，为TBI幸存者在整个生命周期内进行适当的定时和个性化干预铺平道路。所获得的知识可以指导努力改善TBI幸存者的健康和生活质量，并帮助患者，家庭和护理系统规划未来。

DESCRIPTION (provided by applicant): Traumatic brain injury (TBI) is a major public health concern in the US, and the current prevalence of TBI in the US is unprecedented. Individuals with TBI experience diverse patterns of early recovery and long- term clinical outcomes, and some TBI survivors experience accelerated cognitive and health decline as they age. Little is known about factors that predict different trajectories of outcome. The extent to which factors associated with cognitive and health decline in older adults in general (e.g., physical inactivity, medical comorbidity) applies to older adults with a history of TBI is not known. Many existing studies face methodological challenges that limit their usefulness in evaluating cognitive and health outcomes over time, such as small sample sizes, limited follow-up, use of imprecise functional measures, and application of traditional regression approaches whose assumptions are typically not met in longitudinal clinical studies. Our current knowledge of TBI outcomes is confined by these limitations. Recent methodological developments in psychometrics and statistical modeling can be applied to existing data sets, as proposed here, to significantly advance understanding of TBI outcomes and the factors that influence these outcomes over time. The proposed research and career development plan will first evaluate and account for measurement imprecision in commonly used TBI outcome measures, and then evaluate trajectories of temporal change in cognitive and health outcomes for individuals with TBI using advanced statistical methods ideally suited to this purpose. The research and career development plan outlined in this application consists of four complementary objectives that will be implemented during the award period. Objective 1 aims to develop proficiency in the application of advanced psychometric methods to evaluate and adjust for measurement error and bias in commonly used TBI assessment tools. Objective 2 is to acquire mastery in applying sophisticated statistical methods that are capable of evaluating longitudinal relationships among factors that influence TBI outcomes over time, and relate individual clinical trajectories to postmortem neuropathological features of TBI. Objective 3 involves establishing broad fluency in related disciplines of neuropathology, neuroimaging, and genetics that are necessary for interdisciplinary TBI research. Objective 4 is to secure independent research funding. Results from the research related to this K01 award will advance knowledge regarding potentially modifiable factors that are associated with heterogeneity in clinical outcomes over time after TBI, paving the way for appropriately timed and individually tailored interventions throughout the lifespan for TBI survivors. The knowledge gained can direct efforts to improve health and life quality for TBI survivors, and to help patients, families, and care systems plan for the future.