{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:19:31Z","timestamp":1787570371144,"version":"build-2736575974"},"reference-count":47,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82404354"],"award-info":[{"award-number":["82404354"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273710"],"award-info":[{"award-number":["82273710"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate whether immunosuppressant (IS) use contributes to the inverse association between rheumatoid arthritis (RA) and Alzheimer's disease (AD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed NHANES 2011\u20132014 data, including 217 RA patients aged \u2265\u200960\u2009years on prescription medications. Cognitive function was assessed using the Digit Symbol Substitution Test (DSST), CERAD, Animal Fluency Test (AFT), and a global cognition\n                      <jats:italic>z<\/jats:italic>\n                      \u2010score (\n                      <jats:italic>Z<\/jats:italic>\n                      \u2010score). Associations between IS use and cognition were evaluated using multivariable linear regression. Additionally, two\u2010sample Mendelian randomization (TSMR) and multivariable MR (MVMR) analyses were performed with GWAS datasets for RA, AD, and IS to examine potential causal effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We observed that patients with RA using IS performed better in\n                      <jats:italic>z.DDST<\/jats:italic>\n                      (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      : 0.335,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.036) and\n                      <jats:italic>Z<\/jats:italic>\n                      \u2010score (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      : 0.214,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.032) after adjusting for covariates, with sex\u2010specific differences in cognitive domains. TSMR indicated that genetically predicted RA was associated with lower AD risk (OR: 0.936,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20094.531E\u221204), and this effect was largely mediated by IS use. MVMR further validated the independent neuroprotective effect of IS on AD (OR\u2009=\u20090.884,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003) after adjusting for glucocorticoid and NSAID use, while these other medications showed no significant association with AD risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These 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.<\/jats:p>\n                  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