The field of neuroimmunology has seen great advances in the care and treatment of persons with multiple sclerosis (MS) over the past two decades. However, cognitive impairment and fatigue remain prevalent and impactful chronic symptoms even when other disease aspects, such as radiologic disease activity or clinical relapses, are well-controlled (Fuchs et al., 2024; Meijboom et al., 2024).

Cognitive impairment or dysfunction is estimated to have a prevalence of 34-65 % in adults with MS (Benedict et al., 2020), while self-reported fatigue is present in 74 % (Hadjimichael et al., 2008). These symptoms are closely related to a wide range of socioeconomic outcomes, including decreased employment, socioprofessional attainment, and income, fewer social activities, more difficulty with basic household and financial activities, and higher medical costs (Caceres et al., 2014; DeLuca et al., 2020; Krause et al., 2019; Rodriguez Llorian et al., 2023; Salter et al., 2023; Wasem et al., 2024). Additionally, perceived or objective cognitive impairment and higher levels of fatigue are often strongly intertwined with depression and lower health-related quality of life (Nourbakhsh et al., 2016; Simioni et al., 2007; Wynia et al., 2008). For these reasons, potential improvement in cognition and physical fatigue are highly valued in treatment decisions by persons with MS (Li et al., 2024; Tervonen et al., 2023).

This has led to interest on what non-pharmaceutical or pharmaceutical treatments may improve cognition and fatigue in MS. The role of disease-modifying therapies (DMTs) in the treatment of cognition and fatigue in MS is still being evaluated. Several studies have noted potential objective cognitive benefit over a period of a few years with certain DMTs (including high efficacy DMTs such as natalizumab, alemtuzumab, and sphingosine-1-phosphate receptor modulators) (Benedict et al., 2025; Cree et al., 2022; DeLuca et al., 2021; Johnen et al., 2019; Labiano-Fontcuberta et al., 2022; Sandi et al., 2024; Wilken et al., 2023). However, a systematic review and meta-analysis found this effect to be small to moderate, without significant differences between therapies of different efficacy. Conclusions were limited by the lack of high quality evidence (Chen et al., 2020; Landmeyer et al., 2020). This is also true for the impact of DMTs on fatigue (Cruz Rivera et al., 2023; Elkhooly et al., 2023; Machtoub et al., 2024; Meca-Lallana et al., 2024).

We hypothesized that the impact of DMT efficacy on these chronic symptoms may be most apparent when used initially or early in the course of MS, and this effect would be magnified when viewed over a longer follow-up time interval. To assess this, we conducted an electronic cross-sectional survey of persons with MS. This allowed a long duration of time after DMT initiation and a broad sampling of participants. We aimed to assess the potential demographic and clinical factors, including initial choice of DMT, that contribute to self-reported quality of life related to cognitive function and fatigue.