Structural MRI signature of late- versus adult-onset multiple sclerosis: a multiparametric study.

BACKGROUND

Structural MRI differences between late-onset multiple sclerosis (LOMS; onset ≥ 50 years) and adult-onset MS (AOMS) patients remain incompletely characterized, particularly regarding tissue damage distribution and relationship with clinical and cognitive outcomes.

OBJECTIVES

To compare the structural MRI profile of LOMS and AOMS patients within a multiparametric framework including age-matched healthy control (HC) groups, and to examine MRI-clinical associations.

METHODS

Forty LOMS patients, 195 sex- and disease duration (DD)-matched AOMS patients, and 175 age-matched HC (HC-LO = 50; HC-AO = 125) underwent 3 T MRI and clinical-cognitive assessment. Analyses included white matter (WM) lesion volume (T2-LV) and distribution, volumetric measures, tract-based spatial statistics, and voxel-based morphometry. Voxel-wise analyses assessed group differences and associations with DD, Expanded Disability Status Scale (EDSS), and Symbol Digit Modalities Test (SDMT) (p < 0.05, FWE-corrected).

RESULTS

Both MS groups showed higher T2-LV, widespread WM microstructural abnormalities. and lower total, gray matter (GM), and deep GM volumes than age-matched HC (pFDR ≤ 0.015). LOMS patients showed higher lesion frequency in the left superior longitudinal fasciculus (SLF) than AOMS patients (pFWE = 0.003). Onset category × disease status interaction revealed higher T2-LV (pFDR = 0.005) and more pronounced regional GM atrophy in motor-insular-subcortical regions in the LOMS versus AOMS groups (pFWE ≤ 0.040). In LOMS patients, longer DD correlated with higher lesion frequency in the left SLF and mean diffusivity in several WM tracts (pFWE < 0.05). In AOMS patients, higher EDSS and lower SDMT scores related to higher lesion frequency in commissural tracts and thalamic-hippocampal atrophy (pFWE ≤ 0.040).

CONCLUSION

LOMS patients exhibit higher T2-hyperintense WM lesion burden and more pronounced regional GM atrophy than AOMS patients, despite similar DD and no detectable global GM differences, potentially reflecting combined MS-related damage and age-related processes shaping a more severe structural MRI profile.