Comparing the pathology, clinical and demographic characteristics of younger and older-onset multiple sclerosis

Objective: Older people with multiple sclerosis have a less active radiological and clinical presentation, but many still attain significant levels of disability; but what drives worsening disability in this group? Methods: We used data from the UK MS Register to characterise demographics and clinical features of late-onset multiple sclerosis (LOMS; symptom onset at ≥50 years), compared to adult-onset MS (AOMS; onset18-49 years). We performed a pathology study of a separate MS cohort with a later onset (n=18, mean age of onset 54 years) versus AOMS (n=23, age of onset 30 years). Results: In the Register cohort there were 1608 (9.4%) with LOMS. When compared with AOMS, there was a lower proportion of females, a higher proportion of primary progressive MS, a higher level of disability at diagnosis (median MS impact scale 36.7 v 28.3, p<0.001), and a higher proportion of gait-related initial symptoms. People with LOMS were less likely to receive a high efficacy disease modifying treatment and attained substantial disability sooner. Controlling for age of death and sex, neuron density in the thalamus and pons decreased with onset-age, whilst actively demyelinating lesions and compartmentalised inflammation was greatest in AOMS. Only neuron density, and not demyelination or the extent of compartmentalised inflammation, correlated with disability outcomes in older-onset MS. Interpretation: The more progressive nature of older-onset MS is associated with significant neurodegeneration but infrequent inflammatory demyelination. These findings have implications for the assessment and treatment of MS in older people. This article is protected by copyright. All rights reserved.