Methotrexate and relative risk of dementia amongst patients with rheumatoid arthritis: a multi-national multi-database case-control study

Research output: Contribution to journalArticlepeer-review


  • Danielle Newby
  • Daniel Prieto-Alhambra
  • Talita Duarte-Salles
  • David Ansell
  • Lars Pedersen
  • And 13 others
  • Johan Van Der Lei
  • Mees Mosseveld
  • Peter Rijnbeek
  • Glen James
  • Myriam Alexander
  • Peter Egger
  • Jana Podhorna
  • Robert Stewart
  • Gayan Perera
  • Paul Avillach
  • Solène Grosdidier
  • Simon Lovestone
  • Alejo J. Nevado-Holgado

Colleges, School and Institutes


Background: Inflammatory processes have been shown to play a role in dementia. To understand this role, we selected two anti-inflammatory drugs (methotrexate and sulfasalazine) to study their association with dementia risk. Methods: A retrospective matched case-control study of patients over 50 with rheumatoid arthritis (486 dementia cases and 641 controls) who were identified from electronic health records in the UK, Spain, Denmark and the Netherlands. Conditional logistic regression models were fitted to estimate the risk of dementia. Results: Prior methotrexate use was associated with a lower risk of dementia (OR 0.71, 95% CI 0.52-0.98). Furthermore, methotrexate use with therapy longer than 4 years had the lowest risk of dementia (odds ratio 0.37, 95% CI 0.17-0.79). Sulfasalazine use was not associated with dementia (odds ratio 0.88, 95% CI 0.57-1.37). Conclusions: Further studies are still required to clarify the relationship between prior methotrexate use and duration as well as biological treatments with dementia risk.


Original languageEnglish
Article number38
Pages (from-to)38
JournalAlzheimer's Research and Therapy
Publication statusPublished - 6 Apr 2020


  • Anti-inflammatory drugs, Case-control study, Dementia, DMARDs, EMIF, European Medical Information Framework, Inflammation, Methotrexate, Rheumatoid arthritis, Sulfasalazine