Longitudinal surface-based morphometry reveals potential MRI biomarkers correlated with multidimensional brain health...

Characterizing longitudinal brain changes linked to brain health requires identifying structural and neuroanatomical biomarkers. This study aimed to identify MRI-based neuroanatomical correlates associated with longitudinal change in the BrainHealth Index (BHI), a multidimensional measure of cognition, emotional well-being, and social connectedness, and explore their potential as surrogate markers of brain health trajectories in a naturalistic cohort. We investigated neuroanatomical correlates of BHI using longitudinal surface-based morphometry in 190 healthy adults (aged 20-70). We hypothesized that baseline brain morphology would predict BHI performance and that longitudinal BHI changes would correlate with morphometric changes. Participants underwent up to five MRI scans over four years. Surface-based analyses quantified changes in cortical volume, thickness, sulcal depth (SD), gyrification index (GI), and fractal dimension (FD). Vertex-wise regressions tested associations between baseline BHI and morphometric changes, and between longitudinal BHI changes and morphometric features, controlling for age, sex, education, and scan interval. In males, baseline BHI was associated with increased FD over time in the left inferior parietal cortex. In the whole group, BHI gains correlated with increased GI in the left insula and posterior cingulate. In females, BHI improvements were linked to greater SD in the left precuneus, middle temporal, and right cingulate gyri. A sex-specific interaction showed BHI gains in males associated with increased GI in the left insula and temporal cortices. These findings highlight FD, GI, and SD as potential MRI biomarkers for tracking changes in brain health, revealing sex-specific neuroanatomical associations with BHI improvements in regions such as the insula and precuneus.