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.

Public Health Relevance

Geriatric traumatic brain injury (TBI) is a serious public health issue, yet current metrics used to guide TBI care (and withdrawal of care) are not accurate in older patients, leading to arbitrary care decisions and dramatic variation in mortality and outcome across centers. This proposal directly addresses major knowledge gaps by launching a prospective cohort study of geriatric TBI that will apply established geriatric research methods to enroll and track even the frailest patients, thereby advancing knowledge of the comprehensive natural history, and identifying key predictors of outcome, diagnostic and prognostic biomarkers, and the underlying neuropathology of this serious and under-studied condition. The findings of this study have the potential to directly save lives and improve outcomes by developing and validating age-appropriate metrics to guide clinical care of older adults with TBI.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Bellgowan, Patrick S F
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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