Traumatic Brain Injury and The Aging Brain: Predictors of Clinical Trajectories

 描述(由申请者提供)：在这份Paul B.Beeson以患者为导向的研究职业发展奖(K23)申请中，申请者要求5年的研究和工资支持，以提供受保护的时间和专门的培训，以研究创伤性脑损伤(TBI)对老化大脑的影响。长期的职业目标是成为脑损伤和脑老化研究领域的领先者，专注于脑损伤后神经变性的临床预测因素和机制。这项研究计划的具体长期目标将是发现治疗和预防高危、脆弱、老年成年人脑外伤后认知、行为、运动和功能衰退的新靶点。虽然应聘者是一名接受过奖学金培训的行为神经学家，在该领域及相关领域拥有丰富的工作经验，但在以下三个具体领域中，进一步培训对于取得最佳成功至关重要：(1)研究方法和生物统计学方面的高级培训；(2)老龄化流行病学方面的高级培训，重点是跨学科的神经学和老年病预测因素和结果；以及(3)以脑损伤为重点的研究。与她的指导团队一起，候选人制定了一套严格的培训计划，其中包括以下概述的研究计划、正式的课程作业、一对一教程以及多学科研究小组会议、期刊俱乐部和会议。本申请的直接目标是获得足够的初步数据和技能以供提交 成功申请了NIH R01，并开启了PI的独立研究生涯。值得注意的是，脑外伤每年影响近200万美国人，其发病率在晚年最高。尽管脑外伤日益被认为是各种神经退行性疾病的重要危险因素，尤其是痴呆症和帕金森氏病，但急性或急性脑损伤后老年人认知、行为、运动和功能轨迹的病因和模式 远端脑外伤以及这些轨迹的临床预测因子在很大程度上是未知的。这种知识差距阻碍了对脑外伤后神经退行性疾病的诊断、治疗和预防的研究。这项拟议的研究试图通过以下两个具体目标来解决这一关键的知识差距：(1)定义老年人急性脑损伤后的详细临床轨迹和轨迹预测因子，(2)定义老年人远程脑损伤后轨迹的详细临床轨迹尝试和预测因素。这项创新工作将导致对老年人急性和远程脑损伤后特定认知、行为、运动和功能结果的理解取得重大进展，将确定这些结果的潜在可修改临床预测因素，并可能产生关于这些结果的治疗策略或生物学基础的新假设。因此，这项研究的结果将直接指导患有急性或远程脑损伤的老年人的临床评估、预测和风险分层，并将促进治疗或预防脑损伤后神经变性的研究。

 DESCRIPTION (provided by applicant): In this Paul B. Beeson Patient-Oriented Research Career Development Award (K23) application, the applicant requests 5 years of research and salary support to provide protected time and dedicated training to study the effects of traumatic brain injury (TBI) on the aging brain. The long-term career goal is to become a leader in the nascent field of the study of TBI and brain aging with a focus on clinical predictors and mechanisms of post-TBI neurodegeneration. The specific long-term goal of this research program would be to uncover novel targets for treatment and prevention of post-TBI cognitive, behavioral, motor, and functional decline in high-risk, vulnerable, aging adults. While the candidate - a fellowship-trained behavioral neurologist with a record of productivity in this and related fields - is uniquely qualified to pursue this career trajectory, there are three specific areas in which further training will be critical for optimal success: (1) advanced training in research methods and biostatistics, (2) advanced training in epidemiology of aging with a focus on inter- disciplinary neurological and geriatric predictors and outcomes, and (3) TBI-focused research. Together with her mentoring team, the candidate has developed a rigorous training program that includes the research plan outlined below, formal coursework, one-on-one tutorials, and multi-disciplinary research group meetings, journal clubs, and conferences. The immediate goals of this application are to acquire sufficient preliminary data and skills to submit a successful NIH R01 application and to launch the PI's independent research career. Remarkably, TBI affects nearly 2 million American each year with the highest incidence in late life. While TBI is increasingly recognized as an important risk factor for a variety of neurodegenerative diseases, most notably dementia and Parkinson's disease, the etiology and pattern of cognitive, behavioral, motor, and functional trajectories of older adults after acute or remote TBI as well as clinical predictors of these trajectories are largely unknown. This knowledge gap has stunted research on diagnosis, treatment, and prevention of post-TBI neurodegenerative diseases of aging. The proposed research seeks to address this critical knowledge gap via the following 2 specific aims: (1) to define detailed clinical trajectories and predictors of trajectories after acute TBI in older adults, (2) to define detailed clinical trajectries and predictors of trajectories after remote TBI in older adults. This innovative work will lead to significant advances in the understanding of specific cognitive, behavioral, motor, and functional outcomes after acute and remote TBI in older adults, will identify potentially modifiable clinical predictors of these outcomes, and may generate new hypotheses regarding treatment strategies or biological underpinnings of these outcomes. Thus, the results from this research will directly guide clinical assessment, prognostication, and risk-stratification of older adults wth acute or remote TBI and will advance research to treat or prevent post-TBI neurodegeneration.