Associations of Psychological Distress, Cognitive Function, and Physical Activity with Daily Functioning and Quality of Life Across Disability Levels in Multiple Sclerosis

<i>Background and Objectives</i>: Multiple sclerosis (MS) is a chronic neurological disorder causing physical, cognitive, and psychological impairments that affect daily functioning and quality of life (QoL). Psychological distress, cognitive deficits, and reduced physical activity often co-occur, yet their associations with QoL across disability levels are unclear. This study examined these relationships in people with relapsing-remitting MS, stratified by disability severity. <i>Materials and Methods</i>: This cross-sectional study included 149 adults with RRMS. Disability severity was classified as mild, moderate, or severe using the Patient-Determined Disease Steps (PDDS) scale. Psychological distress was assessed using the Depression, Anxiety, and Stress Scale-21 (DASS-21), cognitive function using the Montreal Cognitive Assessment (MoCA), and physical activity using the International Physical Activity Questionnaire (IPAQ). QoL was evaluated using the Multiple Sclerosis International Quality of Life (MusiQoL) questionnaire. Stratified comparative analyses were conducted to examine differences in overall and domain-specific QoL according to levels of psychological distress, cognitive function, and physical activity within disability categories. <i>Results</i>: In participants with mild and moderate disability, higher levels of depression, anxiety, and stress were associated with lower QoL scores, particularly in domains related to activities of daily living, psychological well-being, and symptoms. Higher cognitive function and greater physical activity were associated with more favorable QoL across several domains. In those with severe disability, associations between psychological distress and QoL were less consistent, although stress remained associated with selected QoL domains. <i>Conclusions</i>: Psychological distress, cognitive function, and physical activity show distinct patterns of association with daily functioning and QoL across disability levels in RRMS. Although causal inferences cannot be drawn from this cross-sectional design, disability-stratified analyses provide clinically relevant insights into how these factors co-vary with QoL at different stages of disease severity.