Surface-based morphometry reveals divergent aging trajectories in veterans with and without traumatic brain injury.

Abstract

This study investigates how traumatic brain injury (TBI) alters cortical aging by comparing cortical thickness (CT) and surface area (SA) in 34 brain regions between TBI survivors and age-matched controls. Using a cross-sectional retrospective design, 105 Vietnam Veterans (32 with moderate-to-severe TBI, 73 controls) were analyzed via surface-based morphometry. Principal Component Analysis (PCA) reduced dimensionality, and Multivariate Analysis of Covariance tested group differences while controlling for age, education, depression, Post-Traumatic Stress Disorder, and intracranial volume. Findings revealed divergent morphometric signatures of aging: the proportion of SA variance explained by the first principal component (PC1) was lower in the TBI cohort compared to controls, particularly in parietal and limbic regions. Conversely, CT variance explained by PC1 was higher in TBI compared to controls, with fewer factor loadings in frontal and occipital regions, suggesting differential structural aging patterns due to TBI. Regression analysis demonstrated a stronger association of SA with age in TBI (R2 = 0.619, p = 0.01), while CT exhibited significant negative age-related thinning in TBI-specific regions (R2 = 0.450, p < 0.001). Together, these results suggest that TBI survivors exhibit structured, yet distinct, cortical remodeling, contrasting with the more diffuse patterns seen in normal aging. The differentiated organization of brain areas based on CT and SA points to brain morphology-based biomarkers capable of distinguishing pathological from normative aging trajectories. These biomarkers hold translational potential for refining diagnostic models of brain age and informing targeted neuromodulation or rehabilitation strategies to support cognitive and functional resilience in older adults with TBI.