'Brain age' is a numerical estimate of the biological age of the brain and an overall effort to measure neurodegeneration, regardless of disease type. In multiple sclerosis, accelerated brain ageing has been linked to disability accrual. Artificial intelligence has emerged as a promising tool for the assessment and quantification of the impact of neurodegenerative diseases. Despite the existence of numerous AI models, there is a noticeable lack of comparative imaging data for traditional machine learning versus deep learning in conditions such as multiple sclerosis. A retrospective observational study was initiated to analyse clinical and MRI data (4584 MRIs) from various scanners in a large longitudinal cohort (n = 1516) of people with multiple sclerosis collected from two institutions (Karolinska Institute and Oslo University Hospital) using a uniform data post-processing pipeline. We conducted a comparative assessment of brain age using a deep learning simple fully convolutional network and a well-established traditional machine learning model. This study was primarily aimed to validate the deep learning brain age model in multiple sclerosis. The correlation between estimated brain age and chronological age was stronger for the deep learning estimates (r = 0.90, P < 0.001) than the traditional machine learning estimates (r = 0.75, P < 0.001). An increase in brain age was significantly associated with higher expanded disability status scale scores (traditional machine learning: t = 5.3, P < 0.001; deep learning: t = 3.7, P < 0.001) and longer disease duration (traditional machine learning: t = 6.5, P < 0.001; deep learning: t = 5.8, P < 0.001). No significant inter-model difference in clinical correlation or effect measure was found, but significant differences for traditional machine learning-derived brain age estimates were found between several scanners. Our study suggests that the deep learning-derived brain age is significantly associated with clinical disability, performed equally well to the traditional machine learning-derived brain age measures, and may counteract scanner variability.
Keywords: artificial intelligence; brain age gap; magnetic resonance imaging; neurodegeneration; scanner variability.
© The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain.