Brain age gap correlates with DTI-derived microstructural abnormalities in multiple sclerosis
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Background
Brain age gap (BAG) is increased in multiple sclerosis (MS), but whether it reflects microstructural pathology beyond conventional atrophy remains unclear.
Objective
To test whether BAG is elevated in MS and correlates with conventional and diffusion tensor imaging (DTI) abnormalities relative to healthy controls.
Methods
A case-control study of 43 people with MS and 18 healthy controls was performed. BAG was estimated from T1-weighted MRI using brainageR. Controls were used as MRI reference distributions. MRI values were expressed as deviation z-scores and correlated with BAG within MS. Conventional MRI and DTI domains were analysed using age/sex-adjusted partial correlations with domain-wise Benjamini-Hochberg FDR correction, where appropriate.
Results
BAG was higher in MS than controls (4.79 vs −2.58 years; p<0.001; Cohen’s d=0.84). Within MS, BAG correlated with EDSS (partial r=0.38, p=0.014), disease duration (r=0.39, p=0.011), and lesion volume (r=0.67, p<0.001). Control-referenced conventional MRI abnormalities correlated strongly with BAG, including lower peripheral grey matter volume (r=−0.71, q<0.001), higher CSF volume (r=0.69, q<0.001), and lower grey matter volume (r=−0.67, q<0.001). DTI associations were robust, including higher NAWM mean diffusivity (r=0.66, q<0.001), higher radial diffusivity (r=0.65, q<0.001), and lower fractional anisotropy (r=−0.52, q<0.001).
Conclusions
BAG was elevated in MS and correlated with clinical severity, conventional MRI abnormality, and DTI-derived microstructural injury. These findings support BAG as a biologically relevant MS phenotype extending beyond volumetric atrophy.
