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Cardiorespiratory fitness (measured as peak oxygen uptake; V̇O 2peak) is a well-established health predictor in the general population and in persons with multiple sclerosis (pwMS). We aimed to investigate differences in V̇O 2peak between age groups and the prevalence of V̇O 2peak impairments across the adult lifespan in pwMS compared to age- and sex-matched healthy controls (HC). Cross-sectional study. Data from 469 pwMS (EDSS range 1.0–7.0), who carried out graded cardiopulmonary exercise testing during their rehabilitation stay at the Valens clinic from 07/2010 to 10/2022, were retrospectively analyzed. Data from 21,063 HC were extracted from previously published studies containing normative reference values. With advanced age (i.e., across age groups), a continuous deterioration of V̇O 2peak was observed in both pwMS and HC. Within all age groups, V̇O 2peak was reduced in pwMS compared to HC with deficits ranging from 29 % to 40 % for females (p <.05), and from 30 % to 41 % for males (p <.05). However, no age ∗ group interaction was observed in neither males (p =.626) nor females (p =.557). With V̇O 2peak impairments defined as values below the 5th percentile of HC, a high prevalence was observed in pwMS, with values ranging from 48 % to 100 % across age groups. The present data provide evidence for a parallel deterioration of V̇O 2peak in pwMS and matched controls with advancing age, coinciding with a high prevalence of impairments in V̇O 2peak already present in young adulthood in pwMS. Understanding the extent of impairments as well as the age trajectories of cardiorespiratory fitness in pwMS is crucial for designing optimal rehabilitative and preventive interventions. [ABSTRACT FROM AUTHOR]

• Predictors of six-month change in physical and mental HRQoL were investigated. • Predictors were assessed at clinic entry for a three-week rehabilitation stay. • Physical HRQoL and depressive mood predicted six-month change in physical HRQoL. • Mental HRQoL and time since diagnosis predicted six-month change in mental HRQoL. • The regression models explained 18.6 % (physical) and 26.8 % (mental) of the variance. Symptomatic treatment in people with multiple sclerosis (pwMS) requires multidisciplinary rehabilitation to alleviate disease progression and increasing health-related quality of life (HRQoL). However, the participant- and disease-specific factors that predict sustained improvement in HRQoL in pwMS undergoing inpatient rehabilitation remain unclear. Identifying these factors can help individually tailor inpatient rehabilitation programmes. Therefore, the aim of this study was to identify factors of pwMS at clinic entry for a three-week multidisciplinary inpatient rehabilitation that predict the change in physical and mental HRQoL over six months. This is a secondary data analysis of a randomized controlled trial (NCT04356248) conducted at the Valens Rehabilitation Centre, Switzerland. HRQoL was assessed with the Medical Outcome Study 36-item Short Form Health Survey (SF-36) at clinic entry (T 0 ; baseline) and six months after (T 3 ; six-month follow-up). Data for 99 pwMS (mean age in years: 49.60 ± 10.17 SD, mean Expanded Disability Status Scale (EDSS) score: 4.62 ± 1.33 SD, 68.7 % female) were analysed using multiple linear regression. Outcome variables were six-month change in SF-36 Physical (ΔPCS) and Mental Component Scale (ΔMCS) scores. Predictor variables included baseline scores of PCS or MCS, fatigue, anxiety, depressive mood, cardiorespiratory fitness (V̇O 2peak/kg), self-efficacy, smoking status, education level, age, EDSS, sex, time since diagnosis and MS phenotype. The regression model with ΔPCS as outcome variable explained 18.6 % of the variance of the ΔPCS score (p =.003). Lower PCS score (p <.001) and lower depressive mood (p =.032) at baseline predicted higher ΔPCS score. The regression model with ΔMCS as outcome variable explained 26.8 % of the variance of the ΔMCS score (p <.001). Lower MCS score (p <.001) and longer time since diagnosis (p =.048) at baseline predicted higher ΔMCS score. PwMS with lower physical HRQoL and better mood at clinic entry improved most in physical HRQoL over six months. PwMS with lower mental HRQoL and longer time since diagnosis at clinic entry improved most in mental HRQoL over six months. The results of this study contribute to the development of individualized rehabilitation programmes with the aim of maintaining and/or improving HRQoL of pwMS beyond the inpatient rehabilitation stay. [ABSTRACT FROM AUTHOR]