Clinically Active RA, Presence of CVD Linked to Increased Risk for Dementia

Risk for dementia was increased among patients with clinically active rheumatoid arthritis and those with cardiovascular disease.

Clinically active rheumatoid arthritis (RA) and the presence of cardiovascular disease (CVD) are associated with an increased risk for dementia, according to the results of a retrospective population-based cohort study published in The Journal of Rheumatology.

Age, hypertension, depression, and anxiety have been identified as risk factors for dementia.

In this study, researchers sought to evaluate the risk factors for incident dementia in an inception cohort of individuals with RA.

Residents from 8 counties in Minnesota who were at least 50 years of age when they fulfilled the 1987 American College of Rheumatology (ACR) criteria for incident RA, between 1980 and 2014, were followed-up with through medical record review from inclusion until death/migration or December 31, 2019.

Incident dementia was defined as 2 relevant International Classification of Diseases, Ninth or Tenth Revision (ICD-9 or ICD-10, respectively) codes at least 30 days apart. Data regarding sociodemographics, CVD risk factors, disease characteristics, and comorbidities were collected from patients’ medical records.

A total of 886 patients with incident RA and no dementia prior to the RA incidence date were enrolled in the current study. Overall, 65.2% of the participants were women, 95.4% were non-Hispanic White, and 62.5% tested positive for rheumatoid factor and/or anticyclic citrullinated peptide antibody. The mean patient age was 65.1 years.

These findings establish a high-risk phenotype for dementia incidence among patients with RA.

Over a median period of 8.5 years of follow-up, 103 participants developed dementia. The mean patient age at dementia diagnosis was 82.3±7.2 years. After RA incidence, the cumulative incidence of dementia increased by 2% to 3% every 5 years. Following adjustment for sex, age, and year of RA incidence, several risk factors for dementia were identified.

Older age at RA incidence was consistently associated with an elevated risk for dementia (hazard ratio [HR], 1.14 per 1-year increase; 95% CI, 1.12-1.17).

During follow-up, the presence of rheumatoid nodules (HR, 1.76; 95% CI, 1.05-2.95), large-joint swelling (HR, 2.11; 95% CI, 1.33-3.34), hypertension (HR, 1.84; 95% CI, 1.19-2.85), heart failure (HR, 2.72; 95% CI, 1.29-5.74), depression (HR, 2.23;
95% CI, 1.36-3.67), and use of antihypertensive medication (HR, 1.72; 95% CI, 1.13-2.64) at baseline all were significantly associated with the development of dementia.

In addition, large-joint swelling (HR, 2.03; 95% CI, 1.14-3.60), any CVD (HR, 2.25; 95% CI, 1.38-3.66), anxiety (HR, 1.86; 95% CI, 1.16-2.97), and depression (HR, 2.63; 95% CI, 1.76-3.93) at any time following RA incidence increased risk for dementia.

Among CVD disorders, ischemic stroke and heart failure, but not myocardial infarction, significantly increased the risk for dementia. Further, the presence of diabetes mellitus was associated with an approximately 50% increased risk for dementia, but the associations did not achieve statistical significance.

One of the main study limitations was that the population included was approximately 90% White, thus implying that the results of the study may not be generalizable to other populations. Further, because of the retrospective nature of the study, the researchers relied on information available from medical records, which may not have included comprehensive data on several important risk factors.

The study authors concluded, “These findings establish a high-risk phenotype for dementia incidence among patients with RA.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Kodishala C, Hulshizer CA, Kronzer VL, et al. Risk factors for dementia in patients with incident rheumatoid arthritis: a population-based cohort study. J Rheumatol. 2023;50(1):48-55. doi:10.3899/jrheum.220200