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Use of urate-lowering therapies is not associated with an increase in the risk of incident dementia in older adults
  1. Jasvinder A Singh1,2,3,
  2. John D Cleveland2
  1. 1 Medicine Service, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, USA
  2. 2 Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
  3. 3 Division of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
  1. Correspondence to Dr Jasvinder A Singh, University of Alabama, Birmingham, Alabama, USA;{at}

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Few recent studies1–3 reported that hyperuricemia may be protective against dementia, a common disease in the elderly associated with significant morbidity and mortality.4 5 We hypothesised that allopurinol or febuxostat use (the two most common urate-lowering therapies (ULTs)) in the elderly will be associated with a higher risk of dementia.

Study methods for this new user design study (a more robust design than a prevalent user design) were similar to those previously reported.6 Patients were eligible for this retrospective cohort study if they were (1) US residents enrolled in Medicare fee-for-service (covers all Americans ≥65 years) with pharmacy coverage, ie, enrolled in Medicare parts A (inpatient care), B (outpatient doctor and laboratory service) and D (prescription drugs) and not enrolled in a Medicare Advantage Plan (a standard approach for analysis)7 during 2006–2012 and (2) filled a new allopurinol (or febuxostat) prescription with a clean baseline period of 365 days with no exposure to either drug. Incident dementia was identified by new occurrence (no diagnosis in the 183-day baseline period) of an International Classification of Diseases, 9th Revision code, 290.xx, 294.1x or 331.2, a valid approach for dementia studies.8 9 We followed each eligible patient until the loss of Medicare coverage, dementia, death or the end of the study period, whichever came first. We used multivariable-adjusted Cox proportional …

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  • Contributors JAS designed the study, developed study protocol, reviewed analyses and wrote the first draft of the paper. JC performed the data abstraction and data analyses. Both authors made revisions to the manuscript, read and approved the final manuscript.

  • Funding This material is the result of work supported by research funds from the Division of Rheumatology at the University of Alabama at Birmingham and the resources and use of facilities at the Birmingham VA Medical Center, Birmingham, Alabama, USA. The funding body did not play any role in design, in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication.

  • Disclaimer The views expressed inthis article are those of the authors and do not necessarily reflect theposition or policy of the Department of Veterans Affairs or the United Statesgovernment.

  • Competing interests JAS has received research grants from Takeda and Savient, and consultant fees from Savient, Takeda, Regeneron, Merz, Iroko, Bioiberica, Crealta/Horizon and Allergan pharmaceuticals, WebMD, UBM LLC and the American College of Rheumatology. JAS serves as the principal investigator for an investigator-initiated study funded by Horizon Pharmaceuticals through a grant to DINORA, a 501 (c)(3) entity. JAS is a member of the executive of OMERACT, an organisation that develops outcome measures in rheumatology and receives arm’s length funding from 36 companies; a member of the American College of Rheumatology’s (ACR) Annual Meeting Planning Committee (AMPC); Chair of the ACR Meet-the-Professor, Workshop and Study Group Subcommittee; and a member of the Veterans Affairs Rheumatology Field Advisory Committee. JAS is the editor and Director of the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis. JC has no conflicts to declare. There are no non-financial competing interests for any of the authors.

  • Patient consent The IRB waived the need for written informed consent of patients for this database study.

  • Ethics approval The University of Alabamaat Birmingham’s Institutional Review Board approved this study and allinvestigations were conducted in conformity with ethical principles ofresearch. The IRB waived the need for written informed consent of patients forthis database study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement These data can be obtained from the Centers for Medicare and Medicaid Services (CMS) Chronic Condition Data Warehouse. We are ready to share the data with colleagues, after obtaining appropriate permissions from the Centers for Medicare and Medicaid Services (CMS) Chronic Condition Data Warehouse and the University of Alabama at Birmingham (UAB) Ethics Committee, related to HIPAA and privacy policies.