Age and disability accumulation in multiple sclerosis

OBJECTIVES: We tested the hypothesis that age is a prognostic factor with respect to long-term accumulation of disability in multiple sclerosis (MS). METHODS: Kaplan-Meier analysis and binary logistic regression models determined the effect of age at disease onset, age at onset of progression, and current age on attainment of severe disability levels (Disability Status Scale DSS 6-8-10) from the London, Ontario, database (n = 1,023). RESULTS: Older age at relapsing-remitting (RR) phase onset was associated with higher risk of reaching advanced DSS scores. This was independent of disease duration and early relapse frequency but secondary to increased risk of conversion to secondary progressive (SP) MS. Onset at age 40 (odds ratio OR = 4.22) and at age 50 (OR = 6.04) doubled and tripled risks of developing SP, compared to age 20 (OR = 2.05). Younger age at conversion to SPMS was associated with shorter times to high DSS scores from disease onset. The progressive course, unaffected by age at RR onset, was only modestly affected by age at SP onset. Among primary progressive and RR/SP patients, median ages at attainment of DSS scores were strikingly similar: DSS = 6, 49 vs 48 years; DSS = 8, 58 vs 58 years; and DSS = 10, 78 years for both (p = NS for all comparisons). CONCLUSIONS: Development of SP is the dominant determinant of long-term prognosis, independent of disease duration and early relapse frequency. Age independently affects disability development primarily by changing probability and latency of SP onset, with little effect on the progressive course.