Quality of Life in RRMS: Distress, Cognition, and Activity by Disability Stage

In adults with relapsing–remitting multiple sclerosis (RRMS), a cross-sectional cohort study examined whether psychological distress, cognitive screening status, and physical activity align with MS quality-of-life domains and activities of daily living (ADL) differently across disability stages.

Participants were stratified by Patient-Determined Disease Steps (PDDS) as mild (0–3), moderate (4–6), and severe (≥7), and exposures were grouped by DASS-21 severity categories, MoCA <26 vs ≥26, and IPAQ low/moderate/high.

Distress severity showed the clearest and broadest separation in patients with mild and moderate disability. In mild disability, higher anxiety, stress, and depression severity each aligned with lower ADL and lower psychological well-being (PWB) (all p ≤ 0.009). Symptom burden (SYM) was worse with higher anxiety (p=0.001) and higher depression (p=0.003) but not stress (p=0.368); anxiety also related to relationships with friends (RF) (p=0.028), relationship with the healthcare system (RHCS) (p=0.026), and coping (COP) (p=0.030), while higher stress and higher depression were associated with differences in rejection (REJ) (stress p=0.011; depression p=0.004).

In patients with moderate disability, anxiety, stress, and depression again tracked with lower ADL and lower PWB (all p ≤ 0.046), and total MusiQoL declined with increasing anxiety (p=0.006), stress (p=0.002), and depression (p=0.008). SYM increased with anxiety (p<0.001) and stress (p=0.032) but not depression (p=0.269); anxiety related to RF and relationship with family (RFAM) (both p<0.001) and COP (p=0.003), and stress and depression also affected RFAM and COP (all p ≤ 0.001).

In those with severe disability, anxiety and depression were not significantly associated with ADL or QoL outcomes (all p>0.05), while stress remained associated with poorer ADL (p=0.013), lower PWB (p=0.033), and differences in sexual life (SSL) and RHCS (both p=0.016), suggesting a narrower, stress-concentrated signal at higher disability without implying directionality.

Cognitive screening status separated functional independence more consistently than MusiQoL domains, even as low cognition became more prevalent with greater disability (rare in mild, more frequent in moderate, predominant in severe). In mild disability, normal cognition (MoCA ≥26) was associated with higher ADL than low cognition (82.8±9.2 vs 69.5±8.3; p=0.003), with no other significant domain differences. In moderate disability, normal cognition was again associated with higher ADL (77.7±8.9 vs 68.6±10.3; p=0.002), with no significant difference in total MusiQoL. In severe disability, no significant associations were detected except higher SSL in low vs normal cognition (68.3±11.9 vs 50.0±10.0; p=0.030).

Physical activity followed a disability gradient, and within-stratum associations were domain-selective rather than uniform. In mild disability, activity category related to PWB (p=0.029), REJ (p<0.001), and RHCS (p<0.001), with higher activity described as better PWB, lower REJ, and higher RHCS. In moderate disability, activity related to SYM (p=0.013), RF (p=0.025), and RFAM (p=0.041), with higher activity associated with fewer symptoms and better social functioning; total MusiQoL did not differ significantly by activity. In severe disability, no significant activity associations were detected, which may reflect limited power in a small subgroup (n≈15), ceiling effects or response shift, or reduced measurement sensitivity—hypotheses rather than conclusions.

Taken together, this cross-sectional stratified analysis cannot establish causality, independence, mediation, or effect modification without multivariable adjustment or interaction testing, but it can help prioritize where to probe distress, function, cognition, and activity by disability stage.