{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T18:30:01Z","timestamp":1782930601986,"version":"3.54.5"},"reference-count":47,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2023,9,12]]},"abstract":"<jats:p>Background: Evidence suggests patients prescribed calcineurin inhibitors (CNIs) have a reduced prevalence of dementia, including Alzheimer\u2019s disease (AD); however, this result has never been replicated in a large cohort and the involved mechanism(s) and site of action (central versus periphery) remain unclear. Objective: We aim to determine if prescription of CNIs is associated with reduced prevalence of dementia, including AD, in a large, diverse patient population. Furthermore, we aim to gain insight into the mechanism(s) and site of action for CNIs to reduce dementia prevalence. Methods: Electronic health records (EHRs) from patients prescribed tacrolimus, cyclosporine, or sirolimus were analyzed to compare prevalence, odds, and hazard ratios related to dementia diagnoses among cohorts. EHRs from a random, heterogeneous population from the same network were obtained to generate a general population-like control. Results: All drugs examined reduced dementia prevalence compared to the general population-like control. There were no differences in dementia diagnoses upon comparing tacrolimus and sirolimus; however, patients prescribed tacrolimus had a reduced dementia prevalence relative to cyclosporine. Conclusion: Converging mechanisms of action between tacrolimus and sirolimus likely explain the similar dementia prevalence between the cohorts. Calcineurin inhibition within the brain has a greater probability of reducing dementia relative to peripherally-restricted calcineurin inhibition. Overall, immunosuppressants provide a promising therapeutic avenue for dementia, with emphasis on the brain-penetrant CNI tacrolimus.<\/jats:p>","DOI":"10.3233\/jad-230526","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T11:39:34Z","timestamp":1691494774000},"page":"585-597","source":"Crossref","is-referenced-by-count":28,"title":["Reduced Prevalence of Dementia in Patients Prescribed Tacrolimus, Sirolimus, or Cyclosporine"],"prefix":"10.1177","volume":"95","author":[{"given":"Jacqueline D.","family":"Silva","sequence":"first","affiliation":[{"name":"Mitchell Center for Neurodegenerative Disorders, Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA"},{"name":"Pharmacology and Toxicology Graduate Program, University of Texas Medical Branch, Galveston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Taglialatela","sequence":"additional","affiliation":[{"name":"Mitchell Center for Neurodegenerative Disorders, Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Jupiter","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Science, University of Texas Medical Branch, Galveston, TX, USA"},{"name":"Department of Orthopedics and Rehabilitation, University of Texas Medical Branch, Galveston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-230526_ref1","doi-asserted-by":"crossref","first-page":"487","DOI":"10.2147\/NDT.S350939","article-title":"Role of calcium homeostasis in Alzheimer\u2019s disease","volume":"18","author":"Ge","year":"2022","journal-title":"Neuropsychiatr Dis Treat"},{"key":"10.3233\/JAD-230526_ref2","first-page":"245","article-title":"Neuroimmunomodulation by calcineurin in aging and Alzheimer\u2019s 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