Background/Purpose: Growing evidence from observational studies suggests that patients with rheumatoid arthritis (RA) are at increased risk for cognitive impairment and dementia. Longitudinal population-based studies assessing risk factors for Alzheimer’s Disease and related dementias (AD/ADRD) in RA are lacking. We aimed to assess risk factors for incident AD/ADRD in a population-based cohort of patients with incident RA.

Methods: This retrospective population-based cohort study included residents of a geographical area who were at least 18 years of age and met 1987 ACR criteria for RA between 1980 and 2014. All individuals were followed until death, migration, or 12/31/2019. Incident dementia was defined as two ICD-9/10 codes for AD/ADRD at least 30 days apart. Patients with AD/ADRD before RA incidence were excluded (n=12). Information on socio-demographics, RA disease characteristics, ever use of antirheumatic medications (i.e. conventional and/or biologic disease-modifying drugs; glucocorticoids), cardiovascular/cerebrovascular disease (CVD) risk factors, and comorbidities was available from medical records. The definition of any CVD included coronary heart disease (i.e., angina pectoris, coronary artery disease, myocardial infarction [MI], and coronary revascularization procedures), cerebral stroke and chronic heart failure. Cox proportional hazards models were used to examine the association between each of these risk factors and incident ADRD, adjusting for age, sex, and calendar year of RA incidence. Time-dependent covariates were used to represent factors that developed during follow-up.

Results: A total of 1,366 patients with RA (mean age 56 years, 69% females, 64% positive for rheumatoid factor and/or cyclic citrullinated peptide antibody) were included. During the median follow-up of 9.4 years, 107 patients (8%) developed AD/ADRD. Older age (hazard ratio [HR] per one year increase 1.15, 95% confidence interval [CI] 1.13-1.17), ever presence of large joint swelling (HR 2.2, 95%CI 1.2-3.9), diabetes mellitus (HR 1.6, 95%CI 1.02-2.5), any CVD (HR 2.4, 95%CI 1.5-4.0), and particularly stroke (HR 3.2, 95%CI 1.9-5.5) and heart failure (HR 1.8, 95%CI 1.1-3.0) were associated with increased risk of AD/ADRD. Use of low-dose aspirin (HR 2.3, 95%CI 1.4-3.8) was associated with increased risk for AD/ADRD, likely due to confounding by indication for CVD. Sex, race, education, smoking, obesity, extraarticular features of RA, antirheumatic medications, hypertension, dyslipidemia, or MI were not associated with risk of AD/ADRD among RA patients.

Conclusion: Apart from age, a universally recognized risk factor for AD/ADRD, clinically active RA manifesting with large joint swelling and the presence of CVD and diabetes mellitus were associated with elevated risk of AD/ADRD among RA patients. Among CVD conditions, cerebral stroke and chronic heart failure were associated with the risk of ADRD. These findings suggest that in addition to aging, the risk of AD/ADRD in RA may be driven by RA disease-related factors while CVD may be partially mediating these associations. Studies are ongoing to further evaluate the role of systemic inflammation and CVD in AD/ADRD overall and by dementia subtype in patients with RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-factors-for-dementia-in-patients-with-incident-rheumatoid-arthritis-a-population-based-cohort-study/