{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:03:52Z","timestamp":1792796632657,"version":"4.5.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>To evaluate cognitive improvement in patients with rheumatoid arthritis (RA) after 6 months of treatment with tumor necrosis factor (TNF) inhibitors, analyze associated factors, and determine the percentage of patients achieving cognitive improvement.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a single-center prospective observational study conducted over 12 months on 70 RA patients initiating their first biologic disease-modifying antirheumatic drug (bDMARD) with a TNF inhibitor. Cognitive function was assessed at baseline and after 6 months using validated neuropsychological tests, including the Montreal Cognitive Assessment (MoCA) for global cognitive function, the digit span forward and backward tests for attention and working memory, and the Stroop-W, Stroop-C, and Stroop-CW tests for executive function and processing speed. Patient-reported outcomes were assessed using the Hospital Anxiety and Depression Scale (HADS) and the Quality of Life-Rheumatoid Arthritis Scale-II (QOL-RA II). Clinical variables, disease activity measured by the 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP), inflammatory markers including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and patient-reported outcomes were recorded. Associations with average CRP and Health Assessment Questionnaire (HAQ) scores were analyzed throughout the follow-up period. Cognitive improvement was defined as a \u226520% increase in MoCA test scores. Logistic regression was performed to identify factors associated with improvement.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 70 patients (mean age, 56.2 years; 81.4% female) were included. After 6 months, patients showed significant cognitive improvement in a validated questionnaire, namely, the Montreal Cognitive Assessment (MoCA test 23.1 \u00b1 3.6 to 24.1 \u00b1 3.3; <jats:italic>p<\/jats:italic> = 0.001), particularly in the executive and memory domains. Significant improvements were also observed in the digit span forward test (<jats:italic>p<\/jats:italic> = 0.003), digit span backward test (<jats:italic>p<\/jats:italic> = 0.021), Stroop-W test (<jats:italic>p<\/jats:italic> = 0.040), Stroop-C test (<jats:italic>p<\/jats:italic> = 0.014), and Stroop-CW test (<jats:italic>p<\/jats:italic> = 0.035). Improvements in the MoCA were associated with educational level (<jats:italic>B<\/jats:italic> = 2.628; <jats:italic>p<\/jats:italic> &amp;lt; 0.001), average CRP (<jats:italic>B<\/jats:italic> = \u22120.154; <jats:italic>p<\/jats:italic> = 0.002), and average HAQ (<jats:italic>B<\/jats:italic> = \u22120.303; <jats:italic>p<\/jats:italic> = 0.022). Similar associations were found for the other tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>TNF inhibitor therapy in RA patients is associated with significant cognitive improvement, particularly in executive function and memory. These findings highlight the potential cognitive benefits of effective RA treatment and underscore the importance of addressing modifiable risk factors to enhance patient quality of life.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1561140","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T05:14:43Z","timestamp":1744348483000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Impact of TNF inhibitors on inflammation-associated cognitive dysfunction in patients with rheumatoid arthritis: a prospective analysis"],"prefix":"10.3389","volume":"12","author":[{"given":"Natalia","family":"Mena-V\u00e1zquez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Ortiz-M\u00e1rquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Ramirez-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Gillis-Onieva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Cabezudo-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimara","family":"Garc\u00eda-Studer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arkaitz","family":"Mucientes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Manuel","family":"Lisbona-Monta\u00f1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Borreg\u00f3n-Garrido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Ruiz-Lim\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Manrique-Arija","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Cano-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Jes\u00fas","family":"Serrano-Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Fern\u00e1ndez-Nebro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"105298","DOI":"10.1016\/j.jbspin.2021.105298","article-title":"Cognitive impairment in patients with rheumatoid arthritis: a systematic review and meta-analysis","volume":"89","author":"Pankowski","year":"2022","journal-title":"Jt bone spine."},{"key":"B2","doi-asserted-by":"publisher","first-page":"357","DOI":"10.3389\/fnins.2014.00357","article-title":"New insights into the impact of neuro-inflammation in rheumatoid arthritis","volume":"8","author":"Fuggle","year":"2014","journal-title":"Front Neurosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"R263","DOI":"10.1186\/ar4108","article-title":"Disease activity and cognition in rheumatoid arthritis: an open label pilot study","volume":"14","author":"Raftery","year":"2012","journal-title":"Arthritis Res Ther."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e004422","DOI":"10.1136\/rmdopen-2024-004422","article-title":"Impact of inflammation on cognitive function in patients with highly inflammatory rheumatoid arthritis","volume":"10","author":"Mena-V\u00e1zquez","year":"2024","journal-title":"RMD Open"},{"key":"B5","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1007\/s00296-019-04449-8","article-title":"Assessment of cognitive function in female rheumatoid arthritis patients: associations with cerebrovascular pathology, depression and anxiety","volume":"40","author":"Ol\u00e1h","year":"2020","journal-title":"Rheumatol Int."},{"key":"B6","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1002\/acr.23243","article-title":"Cognitive impairment in rheumatoid arthritis: a systematic review","volume":"70","author":"Meade","year":"2018","journal-title":"Arthritis Care Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1007\/s13311-019-00715-6","article-title":"Can disease-modifying anti-rheumatic drugs reduce the risk of developing dementia in patients with rheumatoid arthritis?","volume":"16","author":"Huang","year":"2019","journal-title":"Neurother J Am Soc Exp Neurother."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1007\/s40263-016-0374-z","article-title":"Treatment for rheumatoid arthritis and risk of Alzheimer's disease: a nested case-control analysis","volume":"30","author":"Chou","year":"2016","journal-title":"CNS Drugs."},{"key":"B9","doi-asserted-by":"publisher","first-page":"152083","DOI":"10.1016\/j.semarthrit.2022.152083","article-title":"Incidence of dementia in patients with rheumatoid arthritis and association with disease modifying anti-rheumatic drugs\u2014analysis of a national claims database","volume":"57","author":"Sattui","year":"2022","journal-title":"Semin Arthritis Rheum."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e69123","DOI":"10.1371\/journal.pone.0069123","article-title":"A systematic analysis of the peripheral and CNS effects of systemic LPS, IL-1\u03b2, [corrected] TNF-\u03b1 and IL-6 challenges in C57BL\/6 mice","volume":"8","author":"Skelly","year":"2013","journal-title":"PLoS ONE."},{"key":"B11","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s13760-017-0879-3","article-title":"Central nervous system involvement in rheumatoid arthritis: possible role of chronic inflammation and tnf blocker therapy","volume":"120","author":"Sag","year":"2020","journal-title":"Acta Neurol Belg."},{"key":"B12","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1016\/j.biopsych.2010.06.012","article-title":"A meta-analysis of cytokines in Alzheimer's disease","volume":"68","author":"Swardfager","year":"2010","journal-title":"Biol Psychiatry."},{"key":"B13","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/1471-2377-8-27","article-title":"Rapid improvement in verbal fluency and aphasia following perispinal etanercept in Alzheimer's disease","volume":"8","author":"Tobinick","year":"2008","journal-title":"BMC Neurol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.jocn.2019.08.027","article-title":"Cognitive impairment in patients with rheumatoid arthritis","volume":"69","author":"Vitturi","year":"2019","journal-title":"J Clin Neurosci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1016\/j.jbspin.2010.01.017","article-title":"Improvement of cognition, a potential benefit of anti-TNF therapy in elderly patients with rheumatoid arthritis","volume":"77","author":"Chen","year":"2010","journal-title":"Joint Bone Spine"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.3390\/biomedicines10071729","article-title":"Longitudinal study of cognitive functioning in adults with juvenile idiopathic arthritis","volume":"10","author":"Mena-V\u00e1zquez","year":"2022","journal-title":"Biomedicines"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e0229819","DOI":"10.1371\/journal.pone.0229819","article-title":"Tumor necrosis factor (TNF) blocking agents are associated with lower risk for Alzheimer's disease in patients with rheumatoid arthritis and psoriasis","volume":"15","author":"Zhou","year":"2020","journal-title":"PLoS ONE."},{"key":"B18","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1002\/gps.4793","article-title":"The influence of TNF inhibitors on dementia incidence in patients with rheumatoid arthritis; an analysis from the BSRBR-RA","volume":"33","author":"McGuinness","year":"2018","journal-title":"Int J Geriatr Psychiatry"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1002\/alz.12465","article-title":"Potential long-term effect of tumor necrosis factor inhibitors on dementia risk: a propensity score matched retrospective cohort study in US veterans","volume":"18","author":"Zheng","year":"2022","journal-title":"Alzheimers Dement."},{"key":"B20","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","article-title":"The montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment","volume":"53","author":"Nasreddine","year":"2005","journal-title":"J Am Geriatr Soc."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/09602011.2018.1445650","article-title":"Comparison of methods for estimating premorbid intelligence","volume":"30","author":"Bright","year":"2020","journal-title":"Neuropsychol Rehabil."},{"key":"B22","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1207\/s15327752jpa3905_9","article-title":"The measurement of creativity by the stroop color and word test","volume":"39","author":"Golden","year":"1975","journal-title":"J Pers Assess."},{"key":"B23","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1111\/j.1600-0447.1983.tb09716.x","article-title":"The hospital anxiety and depression scale","volume":"67","author":"Zigmond","year":"1983","journal-title":"Acta Psychiatr Scand."},{"key":"B24","first-page":"1528","article-title":"Health-related quality of life: validity, reliability, and responsiveness of SF-36, 15D, EQ-5D [corrected] RAQoL, and HAQ in patients with rheumatoid arthritis","volume":"35","author":"Linde","year":"2008","journal-title":"J Rheumatol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e004016","DOI":"10.1136\/rmdopen-2023-004016","article-title":"Association between disease-modifying antirheumatic drugs for rheumatoid arthritis and risk of incident dementia: a systematic review with meta-analysis","volume":"10","author":"Xie","year":"2024","journal-title":"RMD Open"},{"key":"B26","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1038\/s41398-024-03153-x","article-title":"Long-term cognitive training enhances fluid cognition and brain connectivity in individuals with MCI","volume":"14","author":"Gozdas","year":"2024","journal-title":"Transl Psychiatry."},{"key":"B27","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.fmre.2022.12.005","article-title":"The clinical features and potential mechanisms of cognitive disorders in peripheral autoimmune and inflammatory diseases","volume":"4","author":"Fan","year":"2024","journal-title":"Fundam Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"54","DOI":"10.3390\/cells13010054","article-title":"The role of TNF-\u03b1 in Alzheimer's disease: a narrative review","volume":"13","author":"Plantone","year":"2023","journal-title":"Cells"},{"key":"B29","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1111\/jnc.13408","article-title":"Tumour necrosis factor-\u03b1-mediated disruption of cerebrovascular endothelial barrier integrity in vitro involves the production of proinflammatory interleukin-6","volume":"136","author":"Rochfort","year":"2016","journal-title":"J Neurochem."},{"key":"B30","doi-asserted-by":"publisher","first-page":"825","DOI":"10.2147\/JPR.S114915","article-title":"Impaired psychomotor ability and attention in patients with persistent pain: a cross-sectional comparative study","volume":"9","author":"Gunnarsson","year":"2016","journal-title":"J Pain Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1136\/ard-2022-223365","article-title":"Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis","volume":"82","author":"Kerschbaumer","year":"2023","journal-title":"Ann Rheum Dis."},{"key":"B32","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/j.reumae.2024.09.002","article-title":"Update of the consensus statement of the Spanish society of rheumatology on the use of biological and synthetic targeted therapies in rheumatoid arthritis","volume":"20","author":"\u00c1lvaro-Gracia \u00c1lvaro","year":"2024","journal-title":"Reumatol Clin."},{"key":"B33","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.semarthrit.2020.11.005","article-title":"C-reactive protein and implications in rheumatoid arthritis and associated comorbidities","volume":"51","author":"Pope","year":"2021","journal-title":"Semin Arthritis Rheum."},{"key":"B34","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.jpsychores.2015.04.008","article-title":"Tumour necrosis factor-\u03b1 inhibitor therapy in chronic physical illness: a systematic review and meta-analysis of the effect on depression and anxiety","volume":"79","author":"Abbott","year":"2015","journal-title":"J Psychosom Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.3390\/ijms22031185","article-title":"Cognitive decline in rheumatoid arthritis: insight into the molecular pathogenetic mechanisms","volume":"22","author":"Basile","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B36","doi-asserted-by":"publisher","first-page":"236","DOI":"10.3899\/jrheum.120871","article-title":"The relationship between cognitive function and physical function in rheumatoid arthritis","volume":"40","author":"Shin","year":"2013","journal-title":"J Rheumatol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1177\/1529100620920576","article-title":"Education and cognitive functioning across the life span","volume":"21","author":"L\u00f6vd\u00e9n","year":"2020","journal-title":"Psychol Sci public Interes."},{"key":"B38","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1001\/jamaneurol.2023.4929","article-title":"Risk factors for young-onset dementia in the UK biobank","volume":"81","author":"Hendriks","year":"2024","journal-title":"JAMA Neurol."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1561140\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T05:14:45Z","timestamp":1744348485000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1561140\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,11]]},"references-count":38,"alternative-id":["10.3389\/fmed.2025.1561140"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1561140","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,11]]},"article-number":"1561140"}}