Cross-Sectional and Longitudinal Brain Scans Reveal Accelerated Brain Aging in Multiple Sclerosis

ABSTRACT Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system. By combining longitudinal MRI-based brain morphometry and brain age estimation using machine learning, we tested the hypothesis that MS patients have higher brain age relative to chronological age than healthy controls (HC) and that longitudinal rate of brain aging in MS patients is associated with clinical course. Seventy-six MS patients, 71 % females and mean age 34.8 years (range 21-49) at inclusion, were examined with brain MRI at three time points with a mean total follow up period of 4.4 years. A machine learning model was applied on an independent training set of 3208 HC, estimating individual brain age and calculating the difference between estimated brain age and chronological age, termed brain age gap (BAG). We also assessed the longitudinal change rate in BAG in MS individuals. We used additional cross-sectional MRI data from 235 HC for case-control comparison. MS patients showed increased BAG (4.4 ±6.6 years) compared to HC (Cohen’s D = 0.69, p = 4.0 × 10 −6 ). Longitudinal estimates of BAG in MS patients suggested an accelerated rate of brain aging corresponding to an annual increase of 0.41 (±1.23) years compared to chronological aging for the MS patients (p = 0.008). On average, patients with MS have significantly higher BAG compared to HC and accelerated rate of brain aging compared to chronological aging. Brain age estimation represents a promising method for evaluation of brain changes in MS, with potential for predicting future outcome and guide treatment.