The RESIST Study: Examining Cognitive Change in Rheumatoid Arthritis Patients with Mild Cognitive Impairment Being Treated with a TNF-Inhibitor Compared to a Conventional Synthetic Disease-Modifying Anti-Rheumatic Drug

Article type: Research Article

Authors: Marr, Calum^a | McDowell, Bethany^a | Holmes, Clive^{b; c} | Edwards, Christopher J.^{b; d; e} | Cardwell, Christopher^a | McHenry, Michelle^f | Meenagh, Gary^g | Teeling, Jessica L.^h | McGuinness, Bernadette^{a; *}

Affiliations: [a] Centre for Public Health, Queen’s University Belfast, Belfast, UK | [b] Faculty of Medicine, University of Southampton, Southampton, UK | [c] Southern Health NHS Foundation Trust, Southampton, UK | [d] NIHR Southampton Clinical Research Facility, Southampton, UK | [e] University Hospital Southampton NHS Foundation Trust, Southampton, UK | [f] Belfast Health and Social Care Trust, Belfast, UK | [g] Northern Health and Social Care Trust, Antrim, UK | [h] Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK

Correspondence: [*] Correspondence to: Bernadette McGuinness, Centre for Public Health, Institute for Clinical Sciences, Queen’s University Belfast, Belfast, BT12 6BA, UK. E-mail: [email protected].

Abstract: Background:Evidence suggests that TNF inhibitors (TNFi) used to treat rheumatoid arthritis (RA) may protect against Alzheimer’s disease progression by reducing inflammation. Objective:To investigate whether RA patients with mild cognitive impairment (MCI) being treated with a TNFi show slower cognitive decline than those being treated with a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD). Methods:251 participants with RA and MCI taking either a csDMARD (N = 157) or a TNFi (N = 94) completed cognitive assessments at baseline and 6-month intervals for 18 months. It was hypothesized that those taking TNFis would show less decline on the primary outcome of Free and Cued Selective Reminding Test with Immediate Recall (FCSRT-IR) and the secondary outcome of Montreal Cognitive Assessment (MoCA). Results:No significant changes in FCSRT-IR scores were observed in either treatment group. There was no significant difference in FCSRT-IR between treatment groups at 18 months after adjusting for baseline (mean difference = 0.5, 95% CI = –1.3, 2.3). There was also no difference in MoCA score (mean difference = 0.4, 95% CI = –0.4, 1.3). Conclusions:There was no cognitive decline in participants with MCI being treated with TNFis and csDMARDs, raising the possibility both classes of drug may be protective. Future studies should consider whether controlling inflammatory diseases using any approach is more important than a specific therapeutic intervention.

Keywords: Alzheimer’s disease, inflammation, mild cognitive impairment, rheumatoid arthritis, tumor necrosis factor-alpha

DOI: 10.3233/JAD-231329

Journal: Journal of Alzheimer's Disease, vol. 99, no. 1, pp. 161-175, 2024