Cognitive and Vascular Functioning Following TBI

This observational study will examine the association of chronic traumatic cerebrovascular injury and cardiovascular risk factors with TBI-related cognitive impairment and vascular dementia. Cerebrovascular, inflammatory, and neurodegenerative blood biomarkers as well as clinical and neuroimaging data

The investigators will enroll 300 Service Members (SMs) and Veterans who participated in the National Intrepid Center of Excellence (NICoE) intensive outpatient program or Defense and Veterans Brain Injury Center/Traumatic Brain Injury Center of Excellence (DVBIC/TBICoE) 15-Year TBI Natural History of TBI Study (NatHx) at least three years prior to the present evaluation and provided prior blood specimens stored for analysis. Following informed consent, participants will undergo semi-structured interviews assessing posttraumatic stress disorder (PTSD) and updated lifetime TBI history, neurological examination, neuropsychological testing, structural Magnetic Resonance Imaging (MRI) T1, T2, fluid attenuated inversion recovery (FLAIR), diffuse tensor imaging (DTI), as well as novel imaging techniques to assess imaging biomarkers of traumatic cerebrovascular injury (TCVI): 1) functional MRI (fMRI)-Blood Oxygen Level Dependent (BOLD) with hypercapnia challenge to measure cerebrovascular reactivity (CVR); and 2) Dynamic Contrast Enhanced-MRI to assess blood brain barrier integrity, and an additional research blood draw \[apolipoprotein E (APOE) genotype; plasma biomarkers including vascular (e.g., vascular endothelial growth factor, von Willebrand Factor, cholesterol, homocysteine), inflammatory (e.g., high sensitivity c-reactive protein, interleukin-6 (IL-6), chitinase-3-like protein 1 (YKL-40)), and neuronal degeneration (e.g., neurofilament light, phosphorylated tau, brain-derived neurotrophic factor, beta amyloid proteins)\]. A medical record review will be conducted specifically for current and past history of cerebrovascular risk factors (e.g., hypertension, diabetes, tobacco use) and psychological conditions (e.g., PTSD, depression). The project will also leverage previously collected data, comparing participants' symptoms, cognitive performance, imaging, and, blood biomarkers to those previously collected through the NICoE, 15-Year study and/or the DOD serum repository, with data from at least two time points on all individuals.

Eligibility Criteria:
Inclusion Criteria:

1. Active duty uniformed SM or Veteran who is currently eligible for treatment at WRNMMC (i.e., Defense Enrollment Eligibility Reporting System (DEERS)-eligible).
2. Ability to read, write, and speak English.
3. Ability to provide informed consent.
4. NICoE Intensive Outpatient Program (IOP) or NatHx Study comprehensive evaluation ≥3 years prior to current evaluation with valid neuropsychological test results.
5. Consent to allow access to prior research data collected through the NICoE TBI Neuroimaging Core Project or NatHx Study and consent to allow access to at least 1 prior blood specimen previously collected through these studies or the DoD Serum Biorepository.

Additional TBI Inclusion Criteria

1. History of at least one mild, moderate, severe, or penetrating TBI \> 3 years prior to enrollment. TBI will be diagnosed if any one of the following criteria immediately after the injury is met and attributed to the brain injury, rather than environmental/psychological/other injury factors (DoD-VA criteria246):

1. Loss of consciousness (LOC) or post-traumatic amnesia (PTA)
2. Alteration of consciousness (AOC)
3. Evidence of neurologic dysfunction
4. TBI-related abnormality on structural neuroimaging (either CT or MRI). Additional Healthy Control Criteria

   1. History of military deployment.
   2. Low history of blast exposure (i.e., \<10 blasts) Additional Blast Control Criteria

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   1. History of significant blast exposure (i.e., exposure to ≥ 10 blasts)

Exclusion Criteria:

1. Disabling neurologic or psychological disorders such as autism, cerebral palsy, developmental disorder, stroke, brain tumor, multiple sclerosis, meningitis, encephalitis, brain abscess, vascular malformation, pre-injury epilepsy, schizophrenia, bipolar disorder, personality disorder
2. Diabetes mellitus requiring drug treatment
3. Hypertension requiring more than 1 antihypertensive drug to control BP
4. History of myocardial infarction or other systemic vasculopathies
5. Dementia diagnosis at initial NICoE/NatHx Study assessment