Cognitive Dysfunction Biomarkers in Patients With Rheumatoid Arthritis: A Systematic Review

During the last years, a growing number of studies have investigated the link between cognitive dysfunction and rheumatoid arthritis (RA), highlighting the potential pathogenic role of several clinical, psychological, and biological factors. We aimed to investigate serological and cerebrospinal fluid biomarkers in humans and its association with cognitive dysfunction in patients with RA.

We performed a systematic review using PRISMA (Preferred Reported Items for Systematic Reviews and Meta-analysis) protocol. A systematic search was conducted in the PubMed/MEDLINE, EMBASE, LILACS, Scopus, and Google Scholar databases from inception up to November 2021. The inclusion criteria for studies were defined based on the participants involved, type of exposure, type of comparison group, outcome of interest, and study design.

Five original studies were included, which provided data from 428 participants. Among plasma proteins, SHH was increased and TTR was reduced in patients with mild cognitive impairment; anti-myelin basic protein and anti-myelin oligodendrocyte glycoprotein negatively correlated with memory, executive function, and attention. S100β negatively correlated with memory and executive functions; some lymphocyte subpopulations positively correlated with attention, memory, and executive functions. Interleukin 2 [IL-2], IL-4, IL-6, and tumor necrosis factor α negatively correlated with memory and positively correlated with executive functions. Interleukin 1β negatively correlated with global cognitive dysfunction and positively correlated with logical thinking. Interleukin 10 and brain-derived neurotrophic factor negatively correlated with memory.

Despite the relative scarcity of studies on this subject and the heterogeneity of results, we identified possible biomarkers for cognitive deficits in the RA population. Further longitudinal studies are warranted to clarify these associations and the establishment of possible biomarkers for cognitive deficits in RA.