Cognitive Function and Disability in People with Multiple Sclerosis: A Systematic Review and Meta-Analysis

Cognitive dysfunction is a common yet under-recognized component of disability in people with multiple sclerosis (PwMS). Although numerous studies have investigated the relationship between cognitive function and physical disability, the findings remain inconsistent. In this systematic review and meta-analysis, we aim to clarify and quantify the association between physical disability and cognitive performance in PwMS, while also examining potential modifiers and the clinical relevance of this relationship.

A systematic literature search in multiple databases identified 16,340 records published up to August 2, 2024. Following a rigorous screening process and application of pre-established inclusion criteria. Data were extracted on cognitive outcomes and disability outcomes. Correlation coefficients were pooled by random-effects models, and subgroup analyses were run as a function of expanded disability status scale (EDSS) severity, disease duration, age, and MS subtype.

There were moderate pooled correlations between EDSS and SDMT (r = -0.42), Mini-Mental State Examination (MMSE) (r = -0.46), and Montreal Cognitive Assessment (MoCA) (r = -0.43). Correlations were also observed for SDMT with 9-Hole Peg Test (9HPT) (r = -0.34), Timed 25-Foot Walk Test (T25FW) (r = -0.23), and Patient-Determined Disease Steps (PDDS) (r = -0.28). Larger cognitive/disability correlations were observed in patients with higher EDSS scores. Sensitivity analyses confirmed the robustness of results, and publication bias was minimal.

Cognitive and physical disabilities in MS are interdependent, particularly in the advanced stages of the disease. Cognitive assessment should be included in regular evaluations, especially in the early stages of the disease, to ensure optimal monitoring and accurate disability assessment.