The impact of cardiovascular and cerebrovascular disease on the risk of dementia in rheumatoid arthritis: A mediation analysis

Abstract

Objective

To examine the role of cardiovascular disease (CVD) as a mediator in the pathway between rheumatoid arthritis (RA) and Alzheimer's disease and related dementias (ADRD).

Methods

This retrospective population-based study included patients over 50 years of age with incident RA, who met the 1987 ACR criteria in 1980–2014. This cohort was matched 1:1 on age, sex and index year to comparators without RA. Information on CVD events was manually extracted from electronic health records. The relationships between RA, CVD and ADRD were examined using Cox proportional hazard models. Time dependent mediation analysis was used to examine the role of CVD as a mediator between RA and ADRD.

Results

1754 individuals were included (877 persons with RA and 877 comparators without RA). During follow-up, 105 patients with RA and 102 individuals without RA developed ADRD; 444 patients with RA and 375 individuals without RA developed CVD. There was a non-significant association between RA and ADRD both without (aHR 1.27, 95 % CI 0.96, 1.69) and with (aHR 1.27, 95 % CI 0.95,1.68) CVD as a time dependent mediator. The mediation effect of any CVD on ADRD risk was not significant (p = 0.84). We found a significant interaction between RA and CVD on the risk of ADRD (aHR 1.95, 95 % CI 1.11, 3.42; p = 0.021).

Conclusions

The risk of ADRD in RA appears to be increased mainly in the presence of CVD. CVD was not a significant mediator on the risk of ADRD in RA. There was a significant synergistic effect of RA and CVD on ADRD risk.