Plasma Phospholipid Metabolites Associate With Functional Outcomes Following Mild Traumatic Brain Injury in Older Adults

Objective: To compare differences using a metabolomics approach in older adults (>= 55) with mild traumatic brain injury (mTBI) to control adults and to identify a signature profile related to functional outcome 3-6 months post-injury. Methods: We performed metabolomics analysis using LC-MS of untargeted aqueous metabolites on plasma samples taken from a parent prospective cohort study. Older adults with mTBI (n = 14) were purposively sampled to include participants with worsening (decrease in GOS-E of at least 1 level) and improved (increase in GOS-E of at least 1 level) outcomes from 3 to 6 months. The data were analyzed using PLS-DA with VIP scores, Random Forest, and spline fit between the different groups as a function of time for exposure on outcome. Results: Separation of comparisons were seen at 24 hours (negative ionization) and 6 months (positive ionization), revealing two metabolites of interest, phosphatidylcholine and phosphatidylethanolamine. Phosphatidylcholine levels were higher in those with mTBI compared to controls (p< 0.05), while lower concentration of phosphatidylethanolamine was seen in those with mTBI compared to controls (p< 0.05). Phosphatidylinositol-3,4,5-trisphosphate was significant in those with mTBI compared to controls (n = 10) based on improved (n = 6) versus worsened (n = 8) outcomes from 3 to 6 months. Conclusion: We identified plasma metabolites related to phospholipid metabolism in older adults following mTBI and associated with long-term functional outcome. These findings may underly pathological mechanisms of outcome differences in older adults who experience mTBI.