Cognitive impairment in rheumatoid arthritis: role of lymphocyte subsets, cytokines and neurotrophic factors.
To what extent the cognitive impairment of rheumatoid arthritis (RA) is modulated by autoimmune and/or inflammatory activity is largely unknown. The aim of this study was to investigate the role of peripheral inflammation on cognitive functions of patients with active (Ac-), controlled (Co-) RA and healthy controls. In a cross-sectional study, 102 RA patients and 30 matched healthy controls were recruited. B and T cell subsets were immunophenotyped by flow cytometry. Plasma cytokines and neurotrophins were measured by flow cytometry and ELISA, respectively. Cognitive performance, depression and stress were evaluated by structured clinical interviews. Generalized linear modeling (GzLM) was used to compare differences between groups and multiple linear regression models were used to explore the predictive value of immune variables on cognitive performance. RA patients had overall cognitive impairment. Of note, the Ac-RA had the poorest performance on digit span (DST) and N-back when compared to Co-RA and control group (DST 9.9 ± 2.1, 12.9 ± 4.2, 15.5 ± 4.7, respectively; N-back 49.2 ± 8.3, 55.5 ± 11.1, 60.8 ± 9.1, respectively, all p < 0.0001). RA patients had expansions of immature B cells (Ac-RA 11.2 ± 7.1, Co-RA: 9 ± 5.7, control 5.9 ± 2.1) and plasma cells (Ac-RA 5.2 ± 2.5, Co-RA 6.9 ± 3.7, control 2.8 ± 1.7) as compared to controls, all p < 0.05. RA patients (controlled and active disease) had higher plasma levels of TNF, IL-2, IL-4, IL-6 and IL-10 than controls (all p < 0.002). RA patients had higher BDNF levels (Ac-RA 17,354.4 ± 5357.3, Co-RA 13,841.2 ± 5953.7, control 11,543.3 ± 3772), but lower GDNF levels [median (interquartile range) Ac-RA 0 pg/ml (0.0), Co-RA 0 pg/ml (4.6) and control 4.7 pg/ml (18.1)] than controls (all p < 0.05). RA patients had global cognitive impairment, which was associated with disease activity and immune changes.
['Petersen|Laura E|LE|', 'Baptista|Talita S A|TSA|', 'Molina|Júlia K|JK|', 'Motta|Julia G|JG|', 'do Prado|Aline|A|', 'Piovesan|Deise M|DM|', 'de Nardi|Tatiana|T|', 'Viola|Thiago W|TW|', 'Vieira|Érica L M|ÉLM|', 'Teixeira|Antonio L|AL|', 'Grassi-Oliveira|Rodrigo|R|', 'Bauer|Moisés Evandro|ME|']
D000328:Adult D000368:Aged D001172:Arthritis, Rheumatoid D060825:Cognitive Dysfunction D003430:Cross-Sectional Studies D016207:Cytokines D005260:Female D005434:Flow Cytometry D006801:Humans D016130:Immunophenotyping D016131:Lymphocyte Subsets D008297:Male D008875:Middle Aged D009414:Nerve Growth Factors D009483:Neuropsychological Tests
Cognitive impairment Rheumatoid arthritis Cytokines T cells Neurotrophins B cells