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Abstract
Objective To determine whether blood-based biomarkers can differentiate older veterans with and without traumatic brain injury (TBI) and cognitive impairment (CogI).
Methods We enrolled 155 veterans from 2 veterans' retirement homes: 90 without TBI and 65 with TBI history. Participants were further separated into CogI groups: controls (no TBI, no CogI), n = 60; no TBI with CogI, n = 30; TBI without CogI, n = 30; and TBI with CogI, n = 35. TBI was determined by the Ohio State University TBI Identification Method. CogI 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], α-synuclein, β-amyloid 42 [Aβ42], and phosphorylated tau [p-tau]) and cytokines (tumor necrosis factor–α [TNF-α], 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 CogI groups differed on CNS-enriched exosome concentration of p-tau, NfL, IL-6, TNF-α (all p < 0.05), and GFAP (p = 0.06), but not on Aβ42 or other markers. Adjusted area under the curve (AUC) analyses found that all significantly associated biomarkers combined separated TBI with/without CogI (AUC, 0.85; 95% confidence interval [CI], 0.74–0.95) and CogI with/without TBI (AUC, 0.88; 95% CI, 0.77–0.99).
Conclusions Increased levels of blood-based, CNS-enriched exosomal biomarkers associated with TBI and CogI 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 p-tau, NfL, IL-6, and TNF-α are associated with CogI.
Glossary
- α-syn=
- α-synuclein;
- Aβ42=
- β-amyloid 42;
- AD=
- Alzheimer disease;
- AUC=
- area under the curve;
- AVLT=
- Auditory Verbal Learning Test;
- CI=
- confidence interval;
- CogI=
- cognitive impairment;
- CTE=
- chronic traumatic encephalopathy;
- GFAP=
- glial fibrillary acidic protein;
- IL-6=
- interleukin-6;
- IL-10=
- interleukin-10;
- LOC=
- loss of consciousness;
- MMSE=
- Mini-Mental State Examination;
- mTBI=
- mild traumatic brain injury;
- NfL=
- neurofilament light;
- NINDS=
- National Institute of Neurologic Disorders and Stroke;
- OSU-TBI-ID=
- Ohio State University TBI Identification Method;
- p-tau=
- phosphorylated tau;
- ROC=
- receiver operating characteristic;
- TBI=
- traumatic brain injury;
- TNF-α=
- tumor necrosis factor–α;
- WAIS-R=
- Wechsler Adult Intelligence Scale–Revised
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Class of Evidence: NPub.org/coe
- Received September 30, 2019.
- Accepted in final form February 27, 2020.
- © 2020 American Academy of Neurology
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