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.
A lifetime history of traumatic brain injury (TBI) is extremely common and is an important risk factor for aging- related neurodegenerative diseases. It is unknown, however, why some patients with TBI remain resilient as they age while others experience devastating decline in cognition, motor, mood, and behavioral function. The proposed work will address this critical knowledge gap by studying predictors of cognitive, motor, mood/behavior, and global function after acute and remote TBI in older adults.
