Most previous multiple sclerosis (MS) brain atrophy studies using MS impact scale 29 (MSIS-29) or symbol digit modalities test (SDMT) have been cross-sectional with limited sets of clinical outcomes.To investigate which brain and lesion volume metrics show the strongest long-term associations with the expanded disability status scale (EDSS), SDMT, and MSIS-29, and whether MRI-clinical associations vary with age.We acquired MRI and clinical data from a real-world Swedish MS cohort. FreeSurfer and SPM Lesion Segmentation Tool were used to obtain brain parenchymal, cortical and subcortical grey matter, thalamic and white matter fractions as well as TWe included 989 persons with MS followed for a median of 9.3 (EDSS), 10.1 (SDMT), and 9.3 (MSIS-29) years, respectively. In a cross-sectional analysis, the strength of the associations of the MRI metrics with the EDSS and MSIS-29 was found to drastically increase after 40-50 years of age. Low baseline regional grey matter fractions were associated with longitudinal increase of EDSS and physical MSIS-29 scores and decrease in SDMT scores and these atrophy measures were stronger predictors than the lesion volumes.The strength of MRI-clinical associations increase with age. Grey matter volume fractions are stronger predictors of long-term disability measures than lesion volumes.