Shift of multiple sclerosis onset towards older age

Objective: To explore whether age at onset increased over time despite a shortened interval from the initial clinical demyelinating event to the diagnosis of multiple sclerosis (MS), as promoted by updated diagnostic criteria. Methods: This was an independent, multicentre, retrospective study based on data from 4345 patients with relapsing-onset MS attending three tertiary MS Clinics in Italy. After stratifying the year of MS onset into four periods (<1991, 1991-2000, 2001-2010, 2011-2021), we analysed the temporal trends in age at onset and interval from onset to diagnosis; we then explored the female-to-male ratio and onset location across different classes of age at onset. Results: We observed an increased mean age at onset, and a shortened mean interval to diagnosis over time (p<0.0001). Accordingly, there were more MS onsets at the older age classes of 40-49, 50-59 and ≥60 years (p<0.0001). In cases with age at onset ≥40 years, we also found an increased female-to-male ratio (p=0.007), more frequent spinal cord (p=0.0004) and less frequent supratentorial onset (p=0.008). Conclusion: Our study shows a forward shift towards an older age at onset of MS, thus suggesting considerable thought on the place-in-therapy of most currently used disease-modifying treatments, and on the standard of care to an older population.