ArticleNeurology2026
Association of Brain Age With Physical Disability and Cognitive Impairment in People With Multiple Sclerosis of the Same Age.
Article in Neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Accelerated Brain Aging Identifies Functional Vulnerability Beyond Chronological Age in Multiple Sclerosis.Sensors (Basel, Switzerland) · 2026Trial
- Mediation Analysis Between Brain Age, Disease-Modifying Factors, and Disability and Cognitive Performance in Multiple Sclerosis.Neurology · 2026Article
- Rethinking prognosis in multiple sclerosis: a multiaxial perspective.Nature reviews. Neurology · 2026Review
- Occupational dust exposure and cerebral small vessel disease: a public health perspective on prevention and early detection.Frontiers in medicine · 2026Review
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesThe 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.
methodsThis 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.
resultsThe study included 116 HC (mean age 52.9 ± 1.1 years, 61% female) and 237 pwMS (mean age 52.9 ± 0.9 years, median disease duration 16.3 years [interquartile range 8.2-24.4] and a median EDSS of 3.5 [interquartile range 2.5-4.0]). Brain-PAD was higher in pwMS compared with HC by 9.7 years (SE = 0.82, 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.
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