Risk Factors for Dementia in Patients With Incident Rheumatoid Arthritis: A Population-Based Cohort Study

Abstract

Objective Growing evidence suggests that patients with rheumatoid arthritis (RA) have increased risk for dementia. We assessed risk factors for incident dementia in an inception cohort of RA. Methods This retrospective population-based cohort study included residents of eight counties in Minnesota who were ≥50 years when they met 1987 ACR criteria for incident RA between 1980-2014 and were followed until death/migration or 12/31/2019. Patients with dementia before RA incidence were excluded. Incident dementia was defined as two relevant ICD-9/ICD-10 codes at least 30 days apart. Data on socio-demographics, disease characteristics, cardiovascular/cerebrovascular disease (CVD) risk factors and comorbidities were abstracted from medical records. Results The study included 886 patients with RA (mean age=65 years, 65% females). During the follow-up period (median=8.5 years), 103 patients developed dementia. After adjusting for age, sex and calendar year of RA incidence, older age at RA incidence (Hazard Ratio (HR):1.14 per 1 year increase, confidence interval (CI):1.12-1.17), rheumatoid nodules (HR:1.76,CI:1.05- 2.95), hypertension (HR:1.84,CI:1.19-2.85), presence of large joint swelling (HR:2.03,CI:1.14-3.60), any CVD (HR:2.25,CI:1.38-3.66), particularly ischemic stroke (HR:3.16,CI:1.84-5.43) and heart failure (HR:1.82,CI:1.10-3.00), anxiety (HR:1.86,CI:1.16-2.97), and depression (HR:2.63,CI:1.76-3.93) were associated with increased risk of dementia. After adjusting for CVD risk factors and any CVD, all covariates listed above were still significantly associated with risk of dementia. Conclusion Apart from age, hypertension, depression, and anxiety, which are universally recognized risk factors for dementia, clinically active RA and presence of CVD were associated with an elevated risk of dementia incidence among RA patients.

Keep It in Mind: Assessing the Risk of Dementia in Patients With Rheumatoid Arthritis and Opportunities for Intervention

“…7,8 In contrast with the effect of CVD on the risk of incident dementia, where increased risk seems to be concentrated at a younger age, 9 older age at RA incidence was associated with an increased risk of dementia. 5 Depression, anxiety, and any CVD at any point during follow-up also were associated with increased risk for dementia. Interestingly, the authors are the first to demonstrate that large joint swelling and the presence of rheumatoid nodules were associated with an increased risk of dementia during follow-up; however, other disease features often associated with more severe disease (eg, severe extraarticular manifestations, erosive disease) did not show this association.…”

“…3 The magnitude of this risk varies across studies, and according to one recent study from the Rochester Epidemiological Project (REP), increased risk has declined over time, narrowing the gap between adults with and without RA. 4 In this issue of The Journal of Rheumatology, Kodishala et al present the results of a retrospective population-based cohort study assessing risk factors for incident dementia in adults with RA from the REP. 5 The REP includes granular data on participants, including diagnosis, comorbid conditions, and treatments, as well as important disease features such as clinical characteristics (eg, erosive disease, extraarticular manifestations) and laboratory markers (eg, presence of rheumatoid factor and/or anticyclic citrullinated peptide antibody, inflammatory markers). Incident dementia, the outcome of interest, was ascertained through the use of International Classification of Disease, 9th and 10th revision codes; despite some limitations, including the inability to distinguish among dementia subtypes, diagnostic code-based algorithms have been shown to have moderate positive predictive value in the identification of all-cause dementia.…”

“…6 Multivariate Cox proportional hazard models were employed to describe risk factors associated with incident dementia in patients with RA, adjusting for relevant covariates, including CVD and CVD risk factors. 5 During a median follow-up of 8.5 years, 11.6% (103/886 patients) of patients with RA received a diagnosis of dementia. 5 Similar to what has been reported in the general population, hypertension, heart failure, depression, and antihypertensive medication use at baseline were associated with an increased risk of dementia, including after adjusting for covariates.…”

“…5 During a median follow-up of 8.5 years, 11.6% (103/886 patients) of patients with RA received a diagnosis of dementia. 5 Similar to what has been reported in the general population, hypertension, heart failure, depression, and antihypertensive medication use at baseline were associated with an increased risk of dementia, including after adjusting for covariates. 7,8 In contrast with the effect of CVD on the risk of incident dementia, where increased risk seems to be concentrated at a younger age, 9 older age at RA incidence was associated with an increased risk of dementia.…”

“…Although the study by Kodishala et al has some inherent methodological limitations (eg, retrospective, homogenous population), the results highlight clinically meaningful risk factors for identifying adults with RA at higher risk for dementia. 5 CVD screening and preventive measures should be addressed in adults with RA, as in all individuals. Screening for depression and anxiety, and referral for further evaluation and treatment also could have a significant impact on clinical care.…”