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  1. C. Kodishala1,
  2. C. A. Hulshizer2,
  3. V. Kronzer1,
  4. J. M. Davis III1,
  5. V. K. Ramanan3,
  6. M. Vassilaki2,
  7. M. Mielke2,3,
  8. C. S. Crowson1,2,
  9. E. Myasoedova1,2
  1. 1Mayo Clinic, Division of Rheumatology, Rochester, United States of America
  2. 2Mayo Clinic, Quantitative Health Sciences, Rochester, United States of America
  3. 3Mayo Clinic, Neurology, Rochester, United States of America


Background Growing evidence from observational studies indicates that patients with rheumatoid arthritis (RA) have a higher risk of developing dementia. However, the incidence of dementia among RA patients has declined in recent years 1. It is unknown if this reflects broader trends of dementia incidence over time, changes in the prevalence or treatment of associated comorbidities, advances yielding better control of inflammation in RA, or other factors (e.g., environmental risk factors). Longitudinal population-based studies assessing risk factors for dementia among RA patients are scarce 2.

Objectives We aimed to identify risk factors for incident dementia in a large inception cohort of patients with RA.

Methods This retrospective population-based cohort study included residents of Olmsted County, MN, who were ≥50 years when they met 1987 ACR criteria for incident RA in 1980-2014. All individuals were followed until death/migration or 12/31/2019. Patients with dementia before RA incidence were excluded (n=12). Incident dementia was defined as two relevant ICD-9/10 codes at least 30 days apart. Risk factors including socio-demographics, RA disease characteristics and medications, cardiovascular/cerebrovascular disease (CVD) risk factors and other comorbidities were abstracted from medical records. Any CVD was defined as coronary heart disease (i.e., angina pectoris, coronary artery disease, myocardial infarction, coronary revascularization procedures, cerebral stroke or heart failure (HF). Association of individual risk factors with incident dementia was examined using Cox proportional hazard models. Three models were utilized: Model 1, adjusting for age, sex, and calendar year of RA incidence; Model 2, adding smoking, obesity, hypertension, diabetes mellitus, and hyperlipidemia to the first; and Model 3, adding ‘any CVD’ to the second. Time-dependent covariates were used to represent factors that developed during follow-up.

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. Mean age at the diagnosis of dementia was 82.3 (7.2) years. The cumulative incidence of dementia increased by 2-3% every 5 years after the diagnosis of RA. Older age at RA incidence (Hazard Ratio (HR) 1.14 per 1 year increase, confidence interval (CI): 1.12-1.17) was consistently associated with risk of dementia. Presence of rheumatoid nodules (HR 1.76, CI: 1.05-2.95), large joint swelling (HR 2.11, CI: 1.33-3.34), hypertension (HR 1.84, CI: 1.19-2.85), HF (HR 2.72, CI: 1.29-5.74), and depression (HR 2.23, CI: 1.36-3.67) at baseline or during the first year after RA incidence were significantly associated with risk of dementia. Large joint swelling (HR 2.03, CI: 1.14-3.60), any CVD (HR 2.25, CI: 1.38-3.66), anxiety (HR 1.86, CI: 1.16-2.97), and depression (HR 2.63, CI: 1.76-3.93) at any time during the disease increased the risk of dementia. Among CVD conditions, stroke (HR 3.16, CI: 1.84-5.43) and HF (HR 1.82, CI: 1.10-3.00) significantly increased risk of dementia. After adjusting for CVD risk factors (Model 2), or CVD risk factors plus any CVD (Model 3), all the covariates listed above were still significantly associated with the risk of dementia.

Conclusion Apart from age, CVD (particularly hypertension), depression and anxiety, which are universally recognized risk factors for dementia, we observed that clinically active RA was associated with an elevated risk of dementia incidence among RA patients. Studies are ongoing to further evaluate the role of systemic inflammation and its interactions with other risk factors in dementia overall and by dementia subtype in patients with RA.

References [1]Kronzer V L et al. Trends in incidence of dementia among patients with rheumatoid arthritis: A population based cohort study. Semin. Arthritis Rheum. 51, 853–857 (2021)

[2]Wallin K et al. Midlife rheumatoid arthritis increases the risk of cognitive impairment two decades later: A population based study J. Alzheimer’s Dis. 31, 669–676 (2012)

Acknowledgements This work was supported by grants from the National Institutes of Health, NIAMS (R01 AR46849) and NIA (R01 AG068192, R01 AG034676).

Disclosure of Interests Chanakya Kodishala: None declared, Cassondra A Hulshizer: None declared, Vanessa Kronzer: None declared, John M Davis III Grant/research support from: Pfizer, Vijay K Ramanan: None declared, Maria Vassilaki Shareholder of: Abbott Laboratories, Johnson and Johnson, Medtronic, and Amgen, Consultant of: F. Hoffmann-La Roche Ltd, Grant/research support from: F. Hoffmann-La Roche Ltd and Biogen, Michelle Mielke Consultant of: Biogen, Brain Protection Company, and LabCorp, Cynthia S. Crowson: None declared, Elena Myasoedova: None declared

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