Background: Some cross-sectional studies show increased odds of cognitive impairment and dementia in patients with rheumatoid arthritis (RA) compared to the general population, while others show the reverse. Furthermore, existing studies have not evaluated trends in incidence of dementia on a longitudinal basis.
Objectives: We aimed to assess the incidence of dementia over time in patients with incident RA and to compare it to those of population-based comparators.
Methods: This population-based, retrospective cohort study included Olmsted County residents with incident RA and non-RA individuals matched on age, sex, and calendar year. All RA cases met 1987 ACR criteria for RA between 1980 and 2009. Index date was the date of RA criteria fulfillment or a corresponding date for referents. All individuals were followed until death, migration, or 12/31/2019. For sensitivity analyses, follow-up of each decade was truncated at eleven years to make the length of follow-up comparable (e.g., the 1980–89 cohort was truncated at 12/31/1999). Incident dementia was defined as an ICD-9/10 code for dementia. Patients with dementia prior to RA incidence/index date were excluded. Cox proportional hazards models calculated hazard ratios (HR) with 95% confidence intervals (CI) for incident dementia by decade, adjusting for age and sex. The cumulative incidence of dementia was assessed, adjusting for the competing risk of death.
Results: The study included 895 persons with RA (mean age 55.3 years; 69% female) followed up for a median of 15.2 years. The 10-year cumulative incidence of dementia in these individuals during the 1980s was 12.7% (95%CI 7.9-15.7%), 1990s was 7.2% (95%CI 3.7-9.4%), and 2000s was 6.2% (95%CI 3.6-7.8%) Patients with incident RA in 2000-09 had markedly lower cumulative incidence of dementia than patients diagnosed in the 1980s (HR 0.57; 95%CI 0.33-0.98). Patients with incident RA were then compared to population-based comparators without RA (N=880, mean age 55.2 years; 68% female) followed up for a median of 16.4 years. The 10-year cumulative incidence of dementia in these individuals in the 1980s was 9.3% (95%CI 4.6-11.9%), in the 1990s was 5.0% (95%CI 2.2-6.3%) and in the 2000s was 7.1% (95%CI 4.3-8.9%). Overall, the risk of dementia in RA patients was significantly higher than in the non-RA persons (HR 1.38; 95%CI 1.04-1.83). When subdivided by decade, the risk of dementia in patients diagnosed with RA was higher than non-RA comparators in the 1980s and 1990s but not 2000s (Figure 1). Sensitivity analysis with truncated follow-up yielded similar results.
Conclusion: Our findings show substantial decline in risk of dementia in patients with RA onset in the 2000s as compared to 1980s, including when compared to the general population comparators. This decline coincides with the advent of novel biologic treatments for RA. Further studies should investigate this association using manual verification rather than billing codes for dementia, and should also elucidate the role of inflammation, autoimmunity, and anti-rheumatic treatments in risk of dementia.
Acknowledgements: This work was funded by grants from the National Institutes of Health, NIAMS (R01 AR46849) and NIA (R01 AG068192, R01 AG034676).
Disclosure of Interests: Vanessa Kronzer: None declared, Cynthia S. Crowson: None declared, John M Davis III Grant/research support from: Pfizer, Maria Vassilaki Shareholder of: Abbott Laboratories, Johnson and Johnson, Medronic and Amgen, Grant/research support from: Roche, Biogen, Michelle Mielke Consultant of: Biogen and Brain Protection Company, Elena Myasoedova: None declared
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