Comprehensive Investigation of the Clinical Course of Traumatic Brain Injury

描述(申请人提供)：创伤性脑损伤(TBI)在美国是一个主要的公共卫生问题，目前在美国的发病率是史无前例的。脑外伤患者经历了不同的早期康复和长期临床结果模式，一些脑外伤幸存者随着年龄的增长经历了认知和健康的加速下降。人们对预测不同结果轨迹的因素知之甚少。一般情况下，与老年人认知和健康相关的因素下降的程度(例如，缺乏运动， 医疗合并症)适用于有脑外伤病史未知的老年人。许多现有的研究面临方法学上的挑战，这些挑战限制了它们在评估认知和健康结果方面的有效性，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，这些方法的假设在纵向临床研究中通常是不满足的。我们目前对脑外伤结果的了解受到这些限制的限制。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，如这里所建议的，以显著促进对脑损伤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说明常用的脑损伤结果测量的不精确性，然后使用非常适合于此目的的先进统计方法评估脑损伤患者认知和健康结果的时间变化轨迹。申请书中概述的研究和职业发展计划由四个相辅相成的目标组成，这些目标将在获奖期内实施。目标1旨在熟练应用先进的心理测量学方法来评估和调整常用的脑损伤评估工具中的测量误差和偏差。目标2是掌握应用复杂的统计学方法，这些方法能够随着时间的推移评估影响脑外伤预后的因素之间的纵向关系，并将个体临床轨迹与脑外伤死后神经病理特征联系起来。目标3涉及在神经病理学、神经影像和遗传学的相关学科上建立广泛的流利性，这些学科是跨学科脑损伤研究所必需的。目标4是获得独立研究资金。与K01奖项相关的研究结果将促进人们对潜在的可修改因素的了解，这些因素与脑损伤后临床结果的异质性相关，为脑损伤幸存者在整个生命周期内进行适当的时机和个性化的干预铺平了道路。所获得的知识可以指导改善脑外伤幸存者的健康和生活质量的努力，并帮助患者、家属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.