Association Between Serum Matrix Metalloproteinase‐3 Levels and Cognitive Function in Patients With Rheumatoid Arthritis

INTRODUCTION: Cognitive impairment is increasingly recognized as a clinically relevant comorbidity in patients with rheumatoid arthritis (RA). Although chronic inflammation has been implicated in cognitive vulnerability, the relationship between RA-related inflammatory markers and cognitive function has not been fully elucidated. METHODS: In this cross-sectional study, patients with RA underwent cognitive assessment using the Mini-Mental State Examination (MMSE). Serum matrix metalloproteinase-3 (MMP-3) and erythrocyte sedimentation rate (ESR) were evaluated as inflammatory markers. Multivariable linear regression analyses were performed to examine factors associated with MMSE score, adjusting for age, sex, educational level, and frailty. Sensitivity analyses included additional adjustments for ESR, renal function, and glucocorticoid use. Mild cognitive impairment (MCI), defined as an MMSE score ≤ 27, was examined using logistic regression models. RESULTS: A total of 130 patients were included, of whom 34 were classified as having MCI. Higher serum MMP-3 levels were associated with lower MMSE scores after adjustment for demographic factors, educational level, and frailty. This association remained significant after additional adjustment for ESR, whereas ESR itself was not associated with MMSE score in fully adjusted models. Higher MMP-3 levels were also associated with increased odds of MCI, and this association remained significant in analyses restricted to female patients. CONCLUSIONS: Serum MMP-3 levels were associated with cognitive function in patients with RA, whereas ESR was not. These findings suggest that RA-related inflammatory activity reflected by MMP-3 may be relevant to cognitive vulnerability beyond nonspecific inflammation. Further longitudinal studies are warranted to clarify temporal relationships and clinical implications of these findings.