Hypothesis
- Battlefield trauma will result in an increased systemic inflammatory load with the ADVANCE cohort.
- There will be a difference in inflammatory signalling across different injury types and severities, e.g., mild TBI, moderate/ severe TBI, non-TBI, and other traumas.
- Poor cardiovascular health (as defined by gold standard Vicorder measures of PWV and PWA, in addition to HRV and derived QRISK scores) is associated with systemic inflammation.
- TBI will negatively impact cardiovascular health, and this will be influenced by systemic inflammation.
- Poor cardiovascular health will be a significant contributor to worse clinical outcomes and will negatively impact brain health.
Summary
The project aims are defined as:
- To define systemic inflammatory load in the ADVANCE cohort from Soma Logic biomarker analysis. To determine if there is a difference in systemic inflammatory signal across TBI exposures.
- To investigate a systemic inflammatory link between TBI and cardiovascular dysfunction, and how this impacts cardiac and brain health (neurodegenerative biomarkers and cognitive outcomes (neuropsychological battery).
The hypotheses for the aims are:
- Battlefield trauma will result in an increased systemic inflammatory load with the ADVANCE cohort.
- There will be a difference in inflammatory signalling across different injury types and severities, e.g., mild TBI, moderate/ severe TBI, non-TBI, and other traumas.
- Poor cardiovascular health (as defined by gold standard Vicorder measures of PWV and PWA, in addition to HRV and derived QRISK scores) is associated with systemic inflammation.
- TBI will negatively impact cardiovascular health, and this will be influenced by systemic inflammation.
- Poor cardiovascular health will be a significant contributor to worse clinical outcomes and will negatively impact brain health.
Using Soma Logic plasma protein analysis, a data-driven approach will be taken in carrying out cluster analysis to define systemic inflammatory load across the whole cohort. Further data-driven cluster analysis will be carried out to compare patterns of inflammatory protein expression across TBI exposures (no TBI, mild TBI, moderate/server TBI) and investigate how this relates to cardiovascular disease risk. Correlations will be investigated between cardiovascular disease risk and trauma-induced systematic inflammatory signalling. I will investigate how neurodegenerative biomarkers (advanced MRI, fluid biomarkers), link to inflammatory signals in the blood (Soma Logic). Mediation analysis will be used to assess whether any potential correlation between reduced HRV and increased neurodegeneration protein expression is mediated by increased microglial-mediated pro-inflammatory signalling. I will compare cardiovascular disease risk (Q-RISK, PWV, PVA, HRV) with clinical outcome measures such as neuropsychological performance and brain health metrics derived from neuroimaging. I will also compare neurodegenerative biomarker outputs between Soma Logic and Simoa platforms.
Keywords
Biomarkers, Traumatic Brain Injury, Inflammation, TBI, Cardiovascular Health