Age and disability accumulation in multiple sclerosis

Abstract

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.

Figure 1. Risk of converting to secondary progressive multiple sclerosis (SPMS) according to age at onset of relapsing-remitting (RR) phase

Binary logistic regression analysis. Odds ratios expressing the risk of converting to SPMS according to increasing age at onset of RR phase. The probability of entering the SP phase increases proportionally with the age at onset.

Figure 2. Ages at attainment of disability endpoints according to type of disease course

Kaplan-Meier survival analysis from birth. Mean (median) age at onset of progression (OPP) and at disability levels in relapsing-remitting (RR)/secondary progressive (SP) and primary progressive (PP) patients. p Values obtained with log-rank test. DSS = Disability Status Scale.