Association of Brain Age With Physical Disability and Cognitive Impairment in People With Multiple Sclerosis of the Same Age
Len Bos, Alle Meije Wink, James H. Cole, Eva Strijbis, Bastiaan Moraal, Joep Killestein, Hugo Vrenken, Bernard M.J. Uitdehaag, Frederik Barkhof, Menno M. Schoonheim, Bas Jasperse
Abstract
BACKGROUND AND OBJECTIVES: The brain-predicted age difference (brain-PAD) is a novel marker of neurodegeneration in multiple sclerosis (MS). Brain-PAD has been associated with clinical disability in heterogeneous MS patient cohorts of varying ages and disease durations. In this study, we investigate the relation between clinical disability and brain-PAD in a unique birth-year cohort of people with MS (pwMS) and healthy controls (HCs) of the same age all born in 1966, eliminating age as a confounding factor. METHODS: This was a cross-sectional cohort study conducted in the Netherlands. Disability was quantified using the expanded disability status scale (EDSS), 9-hole peg test (9HPT), and the timed 25-foot walk test (T25FWT). Cognition was assessed using the Minimal Assessment of Cognitive Function in MS battery. The brain-PAD was calculated by subtracting the person's chronological age from the predicted brain age derived from 3-dimensional T1-weighted brain MRI scans using machine learning (brainageR software). Brain-PAD for HCs and MS subtypes (relapsing remitting, secondary progressive, and primary progressive) were compared using a generalized linear model. The relation between brain-PAD and disease duration and disability and cognitive measures were tested using univariate linear regression. In addition, the clinical explanatory value added by brain-PAD to those of brain parenchymal fraction (BPF) and T2 lesion volume was investigated. RESULTS: < 0.0001). Brain-PAD had added explanatory value over BPF in clinical outcome measures. DISCUSSION: In a cohort unbiased by age differences, greater brain ageing was associated with worse performance on disability and cognitive tests, underscoring the potential of brain-PAD as a marker for neurodegeneration and disease severity in MS.