Variation in systemic biological health risk is associated with white matter integrity differences in young adult veterans.

Biological health risk factors (e.g., hypertension, high cholesterol, insulin resistance, kidney and liver dysfunction) have been associated with reduced brain white matter integrity (WMI) in middle-aged and older adults. However, less is known about how these risk factors may impact WMI in younger populations, a critical time to capture early effects given the increasing prevalence of these conditions in young people. This study assessed relationships between biological health risk markers and global and regional WMI within a sample of 491 young adult post-9/11 Veteran participants 18–40 years of age (Mean ± SD = 30.64 ± 5.05). T1 and diffusion weighted 3T MRI scans were processed using the FreeSurfer image analysis suite and FSL Diffusion Toolbox. Atlas-based regions of interest of WMI were derived from the white matter skeleton using FSL Tract-Based Spatial Statistics. Biological health markers were clustered into four factors using exploratory factor analysis: Factor 1–4 weighted by (1) blood pressure, (2) HDL cholesterol, (3) glucose/protein, and (4) cholesterol/glucose/kidney function, respectively. Factor 2 was associated with reduced global and regional fractional anisotropy (FA), primarily in frontal and parietal regions. Factor 4 was associated with variation in global mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), and showed different regional effects across the WMI indices. The other two factors (factors 1 and 3) were not significantly related to WMI. These findings indicate biological health risk factors may have dissociable influences on global and regional WMI that are observable early in the adult lifespan, suggesting increased risk for accelerated WMI aging.