Abstract
IMPORTANCE: The implications of socioeconomic factors, including educational level, for multiple sclerosis (MS) progression remain unclear. Understanding whether educational level directly affects MS outcomes or is confounded by lifestyle risk factors and treatment choices could inform personalized care strategies. OBJECTIVE: To investigate the association between educational level and outcomes related to MS, including worsening of disability, cognition, and health-related quality of life, after adjusting for potential confounding factors or mediation by lifestyle factors and treatment. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from 2 large, population-based case-control studies conducted in Sweden from April 2005 to December 2019 that used Swedish MS Registry data with detailed clinical and sociodemographic information. Patients with relapsing-onset MS aged 25 years or older at disease onset after 1995 were followed up from diagnosis until April 6, 2022, with a mean (SD) follow-up time of 10.4 (5.4) years. Data analysis was performed from July 2024 to November 2024. EXPOSURE: Educational level categorized as presecondary (9 to 10 years of compulsory school), secondary (2 to 4 years of high school or college), and postsecondary (higher university education) July 2024 to November 2024. MAIN OUTCOMES AND MEASURES: The primary outcome was confirmed disability worsening defined as a 1-point increase in Expanded Disability Status Scale (EDSS) score sustained across 2 follow-up visits at least 24 weeks apart. Secondary outcomes were worsening of health-related quality of life, measured by the MS Impact Scale (MSIS-29) physical and psychological subscale scores, and cognitive disability worsening, measured by a decrease in Symbol Digit Modalities Test (SDMT) score. Cox proportional hazards regression was used to evaluate associations between educational level and disability progression. RESULTS: Of 3695 participants with MS, 2656 (71.9%) were female, with a mean (SD) age at diagnosis of 39.1 (9.1) years. Lower educational level was associated with older age at disease onset (mean [SD] age at onset: 42.2 [10.2] years for presecondary educational level vs 36.0 [8.4] years for postsecondary educational level), worse baseline clinical status (mean [SD] EDSS 2.7 [2.0] for presecondary education vs 1.7 [1.5] for postsecondary education), and lower likelihood of receiving second-line therapies (mean [SD] 164 [36.9%] for presecondary education vs 869 [54.1] for postsecondary education). In unadjusted analyses, lower educational level was associated with faster disability progression (ie, worsening), but this association was no longer significant after adjusting for treatment and lifestyle factors (adjusted hazard ratio [AHR], 1.14; 95% CI, 0.97-1.33). No associations were found between educational level and changes in MSIS-29 scores (AHR, 1.14 [95% CI, 0.90-1.44] for the MSIS-29 physical subscale and AHR, 1.00 [95% CI, 0.79-1.26] for the MSIS-29 psychological subscale) or SDMT performance over the 15-year follow-up (AHR, 1.05; 95% CI, 0.76-1.46). Mediation analysis revealed that treatment and lifestyle factors accounted for 79.9% of the observed association between education level and disability progression. CONCLUSIONS AND RELEVANCE: In this cohort study of participants with MS, observed differences in disability worsening by educational level were largely accounted for by lifestyle and treatment factors, suggesting that educational level itself may not be independently associated with MS progression.