Transforming Research and Clinical Knowledge in Older Veterans with Acute Traumatic Brain Injury (TRACK-VA)

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Acute traumatic brain injury (TBI) in older veterans is an under-recognized public health emergency for Veterans Health Administration (VHA). The highest and fastest rising incidence of TBI in the U.S. is in older adults, mostly due to ground-level falls. Compared with younger patients, older adults with TBI have higher mortality, lower rates of functional recovery, and may be at especially high risk for post-TBI dementia. Details of clinical and biological characteristics of older Veterans with acute TBI are incomplete, and insufficient to implement evidence-based practice guidelines or plan clinical trials. However, pre-existing TBI, medical/psychiatric conditions, and substance use – common in older Veterans – are emerging risk factors for sustaining TBI and for worse outcomes after TBI. There is an urgent need to comprehensively characterize acute TBI in older Veterans presenting to VA hospitals to inform effective interventions to optimize outcomes. Barriers to progress are: 1) Older adults, especially older Veterans, are underrepresented in acute TBI research. The 18-site NINDS-funded Transforming Research and Clinical Knowledge in TBI study (TRACK- TBI; U01NS086090) had no VA sites and, per protocol, excluded older adults with pre-existing conditions; (2) Emerging TBI blood-based and neuroimaging biomarkers have not been validated in older Veterans, many with pre-existing conditions and military relevant exposures that may reduce accuracy. To begin to address age-related barriers to progress, we received funding from NIH for the Transforming Research and Clinical Knowledge in Geriatric TBI (TRACK-GERI; R01 NS110944 2019-2024) study, a 5-year 2-site TRACK-TBI Network prospective cohort of acute geriatric TBI in patients presenting to Level 1 trauma centers. However, this study will not capture patients who present to VAs or non-trauma center Emergency Departments (ED). Thus, TRACK-GERI will not elucidate the unique features of geriatric TBI in Veterans presenting with mostly mild TBI to VA EDs. To fill this gap, we propose to leverage the existing TRACK-TBI Network data and expertise of our exceptional multi-disciplinary team at SFVA/UCSF to achieve these scientific aims: Aim 1: Characterize baseline and 12-mo longitudinal clinical features using TBI Common Data Elements (CDEs) among Veterans age ≥65y enrolled in the TRACK-TBI and TRACK-GERI studies with acute TBI. We will analyze existing data collected at TRACK-TBI’s 18 non-VA Level 1 trauma centers and explore comparisons to civilians (existing geriatric cohort data consists of N>60 Veterans, N>250 civilians).Aim 2: Assemble a new prospective cohort of Veterans age ≥65y presenting to SFVA ED ≤72h after TBI who received CT (“TRACK- VA”) and deeply phenotype clinical and biological features over 12-months using TBI CDEs. Enroll 70 TBI patient/study-partner dyads and 30 matched ED controls (with medical/orthopedic conditions discharged from the ED), perform baseline clinical assessments (pre-injury health, MREs), blood draws (for APOE, proteomic analysis), brain MRI, and assess longitudinal outcomes at 2wk, 3mo, 6mo, and 12mo post-injury. Aim 3: Characterize neuroimaging features of acute geriatric TBI in Veterans using TBI CDEs and quantitative structural and functional MRI. Obtain structural (T1, T2, susceptibility weighted imaging, multi-shell diffusion imaging, diffusion tensor imaging, neurite orientation dispersion and density imaging) and resting-state functional MRI at 2-wks, 6-mo, and 12-mo post-injury in a sub-set of the TRACK-VA cohort (N=50 TBI; N=25 controls). Characterize acute intracranial trauma on 2-week MRI and characterize longitudinal structural and functional changes. Aim 4: Determine accuracy of blood-based GFAP, P-tau, Abeta, and NFL for TBI diagnosis, prognosis of outcome, and disease-monitoring in older Veterans. We will obtain blood at £72h, 6mo, and 12mo post-injury. This project will comprehensively characterize baseline and longitudinal endophenotypes of an intentionally heterogeneous, “real-world,” population of older Veterans presenting with acute TBI. Findings will inform development of effective interventions to optimize outcomes.