Physical disability, cognition, and depression as determinants of quality of life in multiple sclerosis: a cross-sectional study

Background Quality of life (QoL) in multiple sclerosis (MS) is multifactorial, reflecting the combined effects of physical disability, cognitive impairment, and depressive symptoms. While physical disability is a key determinant, the independent contributions of cognition and depression to QoL remain incompletely defined. This study aimed to assess the frequency of cognitive impairment and depressive symptoms in MS and examine their independent impact on QoL beyond physical disability. Methods This cross-sectional study included 242 patients with clinically definite MS who were evaluated using standardized clinical and neuropsychological measures. Physical disability was assessed by the Expanded Disability Status Scale (EDSS), motor function by the Nine-Hole Peg Test (9-HPT) and 25-Foot Walk Test (25-FWT), cognition by the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test (CVLT), and Brief Visuospatial Memory Test-Revised (BVMT-R), depression by the Hamilton Depression Rating Scale (HAM-D), and QoL by the MS Impact Scale (MSIS-29). Hierarchical multiple regression was performed to identify independent predictors of total QoL. In this study, cognitive impairment was defined as performance ≥1.5 standard deviations below normative means on at least one cognitive test, and depressive symptoms as HAM-D ≥ 8. Results Cognitive impairment was present in 47.9% and depressive symptoms in 61.3% of the cohort. EDSS showed the strongest correlation with MSIS-29 total score ( r = 0.698, p < 0.001), followed by HAM-D ( r = 0.438, p < 0.001) and BVMT-R ( r = −0.340, p < 0.001). In regression analysis, physical disability ( β = 0.65, p < 0.001), depression ( β = 0.23, p < 0.001), and processing speed ( β = −0.12, p = 0.009) were independent predictors of QoL, explaining 64% of its variance. Conclusion Although physical disability remains the dominant determinant of QoL in MS, depressive symptoms and cognitive slowing contribute independent and clinically meaningful effects. Routine screening and early intervention for mood and cognitive disturbances are essential to improve overall well-being in patients with MS.