ArticleInternational journal of rheumatic diseases2026
Immunosuppressant Use Mediates Neuroprotection Against Alzheimer's Disease in Rheumatoid Arthritis-A Two-Step Mendelian Randomization and NHANES Study.
Article in International journal of rheumatic diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesTo investigate whether immunosuppressant (IS) use contributes to the inverse association between rheumatoid arthritis (RA) and Alzheimer's disease (AD).
methodsWe analyzed NHANES 2011-2014 data, including 217 RA patients aged ≥ 60 years on prescription medications. Cognitive function was assessed using the Digit Symbol Substitution Test (DSST), CERAD, Animal Fluency Test (AFT), and a global cognition z-score (Z-score). Associations between IS use and cognition were evaluated using multivariable linear regression. Additionally, two-sample Mendelian randomization (TSMR) and multivariable MR (MVMR) analyses were performed with GWAS datasets for RA, AD, and IS to examine potential causal effects.
resultsWe observed that patients with RA using IS performed better in z.DDST (β: 0.335, p = 0.036) and Z-score (β: 0.214, p = 0.032) after adjusting for covariates, with sex-specific differences in cognitive domains. TSMR indicated that genetically predicted RA was associated with lower AD risk (OR: 0.936, p = 4.531E-04), and this effect was largely mediated by IS use. MVMR further validated the independent neuroprotective effect of IS on AD (OR = 0.884, p = 0.003) after adjusting for glucocorticoid and NSAID use, while these other medications showed no significant association with AD risk.
conclusionsThese results suggest that the reduced risk of AD observed in RA patients may be partly related to IS use, highlighting a potential role of IS in improving cognitive function and modulating AD risk.
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