Biomarkers Associated with Longitudinal Cognitive Decline in Veterans with Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) represents an important medical and public-health problem. One cohort particularly affected by TBI are veterans that have returned from the Afghanistan and Iraq wars. The ramifications of TBIs are multifold, with some of the most common known to include neurodegeneration. Blood biomarkers may provide a minimally invasive diagnostic tool to predict accelerated longitudinal neurocognitive decline. Thirty-one veterans were therefore enrolled in a longitudinal study, with their baseline blood assays and neurocognitive status collected between 2005 – 2007. The blood biomarkers tested at baseline included TNF-, IL1-, IL-6, IL-2, pregnenolone, allopregnanolone, progesterone, and APOE isoform status. Two neuropsychological measures of visual attention and a measure of delayed memory were assessed longitudinally in 10 veterans. Pregnenolone and IL-2 levels were found to be lower in veterans with TBI compared with controls. The triple interaction between APOE status, TBI status, and pregnenolone levels was borderline significant, indicating that those with the 4 isoform will have worse outcomes. While all three measures of cognitive decline were greater in TBI subjects, the attentional measures (Stroop interference and Symbol Search) were statistically significant. All blood biomarkers were negatively related to cognitive decline, as expected, although results were not significant, likely due to the small sample size. Results show promise in the use of blood biomarkers as an effective method of predicting cognitive decline based on TBI status. Thus, further work with a larger sample size is warranted, as the blood biomarker levels may predict neuroplasticity changes causing cognitive decline in those with TBI.