Impact of Disease-Modifying Antirheumatic Drugs on Cognitive Function in Older Adults with Rheumatoid Arthritis.

Abstract

Cognitive impairment poses significant challenges for aging populations. Systemic inflammation, a hallmark of rheumatoid arthritis (RA), has been implicated in neurodegeneration through mechanisms including blood-brain barrier disruption, microglial activation, and cytokine-mediated neuronal damage. This review examines the potential impact of disease-modifying antirheumatic drugs (DMARDs) on cognitive function in RA, focusing on the inflammatory pathways linking systemic inflammation to neuroinflammation and cognitive decline. DMARDs, categorized into conventional synthetic (csDMARDs), biologic (bDMARDs), and targeted synthetic (tsDMARDs) classes, modulate immune responses through distinct mechanisms. Evidence suggests that DMARDs, particularly bDMARDs targeting proinflammatory cytokines such as TNF-α and IL-6, may mitigate neuroinflammatory processes and preserve cognitive function. However, the cognitive impact of csDMARDs such as methotrexate is complex, with conflicting reports regarding its role in vascular dementia. Emerging therapies such as Janus kinase inhibitors (JAK-i) offer promise in modulating central inflammation, though clinical evidence remains limited. While some studies highlight protective effects of DMARDs against dementia, findings are inconsistent, hindered by heterogeneity in study design, patient demographics, and cognitive assessment methods. This review underscores the need for personalized treatment strategies, integrating RA management with cognitive health considerations. Future research should prioritize robust, prospective studies with long-term follow-up, incorporating neuroimaging and biomarker analysis to elucidate the mechanisms underpinning DMARD-associated cognitive outcomes. A better understanding of the involved inflammatory pathways in RA and the potential effects of DMARDs could lead to improved therapeutic approaches, enhancing quality of life for patients with RA and potentially benefiting broader strategies in preventing or treating dementia.