Reduced Prevalence of Dementia in Patients Prescribed Tacrolimus, Sirolimus, or Cyclosporine

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8 Scopus citations

Abstract

Background: Evidence suggests patients prescribed calcineurin inhibitors (CNIs) have a reduced prevalence of dementia, including Alzheimer's 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.

Original languageEnglish (US)
Pages (from-to)585-597
Number of pages13
JournalJournal of Alzheimer's Disease
Volume95
Issue number2
DOIs
StatePublished - Sep 12 2023

Keywords

  • Alzheimer's disease
  • TriNetX
  • calcineurin
  • cyclosporine
  • dementia prevalence
  • drug repurposing
  • electronic health records
  • sirolimus
  • tacrolimus

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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