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

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.

• Authors: Carrie B Peltz, Kimbra Kenney, Jessica Gill, Ramon Diaz-Arrastia, Raquel C Gardner, Kristine Yaffe
• Journal: Neurology (Neurology) Vol. 95 Issue 9 Pg. e1126-e1133 (09 01 2020) ISSN: 1526-632X [Electronic] United States
• PMID: 32571850 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2020 American Academy of Neurology.

Chemical References

• Amyloid beta-Peptides
• Biomarkers
• GFAP protein, human
• Glial Fibrillary Acidic Protein
• IL10 protein, human
• IL6 protein, human
• Interleukin-6
• L1CAM protein, human
• MAPT protein, human
• Neural Cell Adhesion Molecule L1
• Neurofilament Proteins
• Peptide Fragments
• SNCA protein, human
• TNF protein, human
• Tumor Necrosis Factor-alpha
• alpha-Synuclein
• amyloid beta-protein (1-42)
• neurofilament protein L
• tau Proteins
• Interleukin-10

Topics

• Aged
• Aged, 80 and over
• Amyloid beta-Peptides (blood)
• Biomarkers (blood)
• Brain Injuries, Traumatic (blood)
• Case-Control Studies
• Cognitive Dysfunction (blood)
• Exosomes (metabolism)
• Female
• Glial Fibrillary Acidic Protein (blood)
• Humans
• Interleukin-10 (blood)
• Interleukin-6 (blood)
• Male
• Mental Status and Dementia Tests
• Neural Cell Adhesion Molecule L1 (metabolism)
• Neurofilament Proteins (blood)
• Neuropsychological Tests
• Peptide Fragments (blood)
• Phosphorylation
• Tumor Necrosis Factor-alpha (blood)
• Veterans
• alpha-Synuclein (blood)
• tau Proteins (blood)