Blood biomarkers of traumatic brain injury and cognitive impairment in older veterans.

Objective: To determine whether blood-based biomarkers can differentiate older veterans with and without traumatic brain injury (TBI) and cognitive impairment (CI). Methods: We enrolled 155 veterans from two veterans’ retirement homes: 90 without TBI and 65 with TBI history. Participants were further separated into CI groups: Controls (no TBI, no CI), n=60; no TBI with CI, n=30; TBI without CI, n=30; and TBI with CI, n=35. TBI was determined by the Ohio State University TBI Identification Method. CI was defined as impaired cognitive testing, dementia diagnosis, or use of dementia medication. Blood specimens were enriched for CNS-derived exosomes. Proteins [neurofilament light (NfL), total tau, glial fibrillary acidic protein (GFAP), alpha synuclein, β-amyloid 42 (Aβ42), and phosphorylated tau (pTAU)] and cytokines [tumor necrosis factor alpha (TNFa), interleukin 6 (IL-6) and interleukin 10] were measured using ultrasensitive immunoassays. Results: Veterans were, on average, 79 years old. In participants with TBI history, 65% had mild TBI; average time from most recent TBI was 37 years. In adjusted analyses, the TBI and CI groups differed on CNS-enriched exosome concentration of pTAU, NfL, IL-6, TNFa (all p Conclusions: Increased levels of blood-based, CNS-enriched exosomal biomarkers associated with TBI and CI can be detected, even decades after TBI. Classification of Evidence: This study provides Class II evidence that in veterans with a history of TBI, CNS-enriched exosome concentration of pTAU, NfL, IL-6, TNFa are associated with cognitive impairment.