Abstract Text: Concussion (i.e., mild traumatic brain injury, or mTBI) is a major public health concern in the United States, especially among the military and sports medicine communities. While the military’s attention has historically focused on blast and war-related TBI, the majority of concussions/mTBIs in service members are actually sustained during military training-related activities. The CARE/SALTOS Integrated (CSI) Study – Military Cohort Tier 2 is a stratified cohort study to longitudinally follow-up on previously assessed military service academy cadets/midshipmen in order to address critical questions surrounding potential long-term effects of concussion/mTBI and/or head impact exposure (HIE) on warfighter brain health. Participants will be stratified on measures of exposure to concussion/mTBI and repetitive HIE or blunt/blast exposure (HIGH EXPOSURE; LOW EXPOSURE). Participants at four military sites will undergo a detailed, in-person research evaluation including clinical assessments, neurologic evaluation, neuropsychological testing, advanced MRI imaging, collection of fluid biomarkers, and genetic testing. This study will advance both translatable processes and knowledge that will identify and ultimately reduce or eliminate acute to late and long-term effects from concussion/mTBI and repetitive HIE.
Aim 1: Prospectively characterize the relationship between concussion(s)/mTBI, repetitive HIE, and brain health outcomes up to 10 years following an athletic and military service academy career in the domains of neurological and psychological health; cognition; quality of life and career/military performance. Hypothesis 1.1 – Individuals with a history of concussion/mTBI and/or HIE will perform worse on measures of neurological and psychological health; cognition; quality of life and career/military performance than those without a concussion/mTBI and/or repetitive HIE history. Hypothesis 1.2 – In those with a concussion/mTBI and/or HIE history, increasing metrics of exposure level (e.g., number of concussions, HIE, extent of blunt and/or blast exposure) will be negatively correlated (dose-response relationship) with measures of neurological and psychological health; cognition; quality of life and career/military performance.
Aim 2: Prospectively characterize the relationship between concussion(s)/mTBI and/or HIE on brain structure and function up to 10 years following an athletic and military service academy career, using advanced neuroimaging (multimodal MRI; genomic and proteomic markers of neurodegeneration and neuroinflammation). Hypothesis 2.1 – Individuals with a history of concussion/mTBI and/or HIE (HIGH EXPOSURE GROUP) will have greater structural and functional brain abnormalities on MRI; and higher levels of genomic and proteomic markers of neuroinflammation and neurodegeneration than those without a history of concussion/mTBI and/or repetitive HIE (LOW EXPOSURE GROUP). Hypothesis 2.2 – In those with a history of concussion/mTBI and/or HIE, increasing metrics of exposure level (e.g., number of concussions, extent of blunt and/or blast exposure) will be correlated (dose-response relationship) with measures of structural and functional brain abnormalities on MRI; and higher levels of genomic and proteomic markers of neuroinflammation and neurodegeneration.
Aim 3: Develop a multidimensional algorithm that predicts brain health up to 10 years after HIE. Hypothesis 3.1 –An array of pre-exposure (e.g., genetic modulators, sex), exposure (e.g., number of concussions, extent of blunt and/or blast exposure), post-exposure (e.g., intercurrent life events, psychological & general health factors), and injury response (e.g., structural/functional MRI abnormalities, neuroinflammatory and neurodegeneration marker burden) variables will predict brain health outcomes. Hypothesis 3.2 – Individuals with a concussion(s)/mTBI and/or HIE history who have additional concussion(s) and/or HIE exposure subsequent to their athletic or MSA career will perform worse on measures of neurological/psychological health; cognition; quality of life and career/military performance than those without additional concussion(s)/mTBI and/or HIE exposure.
