Brain atrophy appears to occur in patients with multiple sclerosis (MS) in excess of that associated with normal ageing, and may be observed early in the clinical course of the disease. The dynamics and tissue specificity of this process remain unclear This preliminary study explored the evolution of brain grey matter (GM) and white matter (WM) volume loss (as fractions of total intracranial volumes) in 13 subjects with relapsing-remitting MS (mean disease duration 1.9 years at first scan), compared with nine normal control (NC) subjects. Subjects were scanned every six months for 18 months. In MS compared with NC subjects, significant differences in WM fractional volumes were observed at baseline (mean - 5.8%, P = 0.008) but no apparent progressive WM tissue loss was detected. In contrast, while no significant differences in GM fractional volumes were observed at baseline, there was significantly greater time-related volume loss in MS compared with NC subjects over the follow-up period (circa - 0.0086 per year in MS subjects, - 0.0021 per year in the NC subjects, difference P = 0.010). These results suggest that while both GM and WM atrophy are seen early in the clinical course of MS, they may not occur concurrently and may evolve at different rates.

BackgroundBrain atrophy occurs in both normal ageing and in multiple sclerosis (MS), but it occurs at a faster rate in MS, where it is the major driver of disability progression. Here, we employed a neuroimaging biomarker of structural brain ageing to explore how MS influences the brain ageing process. MethodsIn a longitudinal, multi-centre sample of 3,565 MRI scans in 1,204 MS/clinically isolated syndrome (CIS) patients and 150 healthy controls (HCs) (mean follow-up time: patients 3·41 years, HCs 1·97 years) we measured 'brain-predicted age' using T1-weighted MRI. Brain-predicted age difference (brain-PAD) was calculated as the difference between the brain-predicted age and chronological age. Positive brain-PAD indicates a brain appears older than its chronological age. We compared brain-PAD between MS/CIS patients and HCs, and between disease subtypes. In patients, the relationship between brain-PAD and Expanded Disability Status Scale (EDSS) at study entry and over time was explored. FindingsAdjusted for age, sex, intracranial volume, cohort and scanner effects MS/CIS patients had markedly older-appearing brains than HCs (mean brain-PAD 11·8 years [95% CI 9·1-14·5] versus -0·01 [-3·0-3·0], p<0·0001). All MS subtypes had greater brain-PAD scores than HCs, with the oldest-appearing brains in secondary-progressive MS (mean brain-PAD 18·0 years [15·4-20·5], p<0·05). At baseline, higher brain-PAD was associated with a higher EDSS, longer time since diagnosis and a younger age at diagnosis. Brain-PAD at study entry significantly predicted time-to-EDSS progression (hazard ratio 1·02 [1·01-1·03], p<0·0001): for every 5 years of additional brain-PAD, the risk of progression increased by 14·2%.Interpretation MS increases brain ageing across all MS subtypes. An older-appearing brain at baseline was associated with more rapid disability progression, suggesting 'brain-age' could be an individualised prognostic biomarker from a single, cross-sectional assessment. Evidence before this studyWe searched Pubmed and Scopus with the terms "multiple sclerosis" and "brain ageing" or "brain age" and "neuroimaging" or "MRI" for studies published before 15 th March 2019. This searched return no studies of brain ageing in multiple sclerosis. We also searched the pre-print server for biology, bioRxiv, and found one manuscript deposited, though this study has yet to appear in a peer-reviewed journal. This study found a strong effect of multiple sclerosis on the apparent age of the brain, though was only cross-sectional, was from a single centre, did not consider disease subtypes and did not consider the relevance of clinical characteristics for brain ageing. Therefore, although there is strong prior evidence of the importance of brain atrophy in multiple sclerosis, there was no information on how the nature of this atrophy relates to brain ageing. Added value of this studyHere we demonstrate for the first time that the progressive atrophy in multiple sclerosis patients results in an acceleration of age-related changes to brain structure....

No abstract

No abstract