Rheumatoid Arthritis, Cognitive Impairment, and Neuroimaging Biomarkers: Results from the Mayo Clinic Study of Aging

J Alzheimers Dis. 2022;89(3):943-954. doi: 10.3233/JAD-220368.


Background: Observational studies suggested that dementia risk in patients with rheumatoid arthritis (RA) is higher than in the general population.

Objective: To examine the associations of RA with cognitive decline and dementia, and neuroimaging biomarkers of aging, Alzheimer's disease, and vascular pathology in adult participants in the Mayo Clinic Study of Aging (MCSA).

Methods: Participants with RA were matched 1:3 on age, sex, education, and baseline cognitive diagnosis to participants without RA. RA cases with MRI were also matched with non-cases with available MRI. All available imaging studies (i.e., amyloid and FDG PET, sMRI, and FLAIR) were included. The study included 104 participants with RA and 312 without RA (mean age (standard deviation, SD) 75.0 (10.4) years, 33% male and average follow-up (SD) 4.2 (3.8) years).

Results: Groups were similar in cognitive decline and risk of incident dementia. Among participants with neuroimaging, participants with RA (n = 33) and without RA (n = 98) had similar amyloid burden and neurodegeneration measures, including regions sensitive to aging and dementia, but greater mean white matter hyperintensity volume relative to the total intracranial volume (mean (SD)% : 1.12 (0.57)% versus 0.76 (0.69)% of TIV, p = 0.01), and had higher mean (SD) number of cortical infarctions (0.24 (0.44) versus 0.05 (0.33), p = 0.02).

Conclusion: Although cognitive decline and dementia risk were similar in participants with and without RA, participants with RA had more abnormal cerebrovascular pathology on neuroimaging. Future studies should examine the mechanisms underlying these changes and potential implications for prognostication and prevention of cognitive decline in RA.

Keywords: Cognitive decline; cognitive impairment; dementia; magnetic resonance imaging; rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aging
  • Alzheimer Disease* / complications
  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / epidemiology
  • Amyloid / metabolism
  • Amyloid beta-Peptides / metabolism
  • Amyloidosis* / pathology
  • Arthritis, Rheumatoid* / complications
  • Arthritis, Rheumatoid* / diagnostic imaging
  • Arthritis, Rheumatoid* / epidemiology
  • Biomarkers
  • Brain / pathology
  • Cognitive Dysfunction* / complications
  • Cognitive Dysfunction* / diagnostic imaging
  • Cognitive Dysfunction* / epidemiology
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neuroimaging
  • Positron-Emission Tomography


  • Amyloid
  • Amyloid beta-Peptides
  • Biomarkers
  • Fluorodeoxyglucose F18