POS0311 NEUROIMAGING BIOMARKERS IN INDIVIDUALS WITH AND WITHOUT RHEUMATOID ARTHRITIS: RESULTS FROM THE MAYO CLINIC STUDY OF AGING
Authors: M. Vassilaki, C. S. Crowson, J. M. Davis, S. Duong, D. Jones, M. Mielke, P. Vemuri, E. Myasoedova
Journal: Annals of the Rheumatic Diseases (2021)

Background: Age-related increase in the burden of systemic inflammation is an established key player and potential treatment target in Alzheimer’s disease (AD) and other age-related dementias. (Dregan, Chowienczyk et al. 2015) Although rheumatoid arthritis (RA) is an autoimmune hyper-inflammatory disease, studies on RA and dementia or vascular neuroimaging biomarkers are lacking. Objectives: To examine the associations between RA and dementia/vascular neuroimaging biomarkers in the Mayo Clinic Study of Aging (MCSA). Methods: The study consisted of 35 RA cases in MCSA and 104 MCSA participants without RA matched 1:3 for age, sex, education, cognitive status (≥50 years old) at baseline and the availability of at least one magnetic resonance imaging (MRI). The primary outcome measures were well established dementia-related neuroimaging biomarkers, including global beta-amyloid (Aβ) using PiB-positron-emission tomography (PET; n=47); neurodegeneration (hypometabolism via FDG-PET (n=45), hippocampal volume (n=139), and cortical thickness via structural MRI [n=138], and cerebrovascular pathology via FLAIR-MRI (white matter hyperintensity [WMH; n=49] burden, subcortical, and cortical infarctions (n=55)). Elevated 11 C-PiB-PET was defined as standardized uptake value ratio ≥1.48 in an Alzheimer’s disease (AD)-related region of interest and reduced AD signature cortical thickness as ≤2.68mm (neurodegeneration; N+). Kruskal-Wallis rank sum and Pearson’s chi-squared tests were used to compare the neuroimaging measures between participants with and without RA. Results: Participants with vs. without-RA did not differ in age, sex, years of education, major comorbidities, Aβ burden, hippocampal volume, and neurodegeneration measures (Table 1). Although the sample size was small, we observed that RA participants (vs. without-RA) had greater mean WMH volume (relative to the total intracranial volume (TIV) (mean (SD) %: 1.12 (0.57) % vs 0.76 (0.69) % of TIV, p=0.011), were more likely to have cortical infarctions (4 vs.1; p=0.013) and had a higher mean number of cortical infarctions (mean (SD): 0.24 (0.44) vs. 0.05 (0.32), p=0.017). Table 1. Participants’ baseline characteristics. With RA Without RA Total p value* Age, mean (SD) 76.3 (7.9) 75.9 (7.9) 139 0.82 Male 13 (37%) 37 (36%) 139 0.87 Education (years), mean (SD) 14.5 (2.5) 14.3 (2.4) 139 0.75 Apolipoprotein E ε4 carrier 6 (17%) 28 (27%) 139 0.24 Cognitively unimpaired 27 (77%) 83 (80%) 110 0.94 Mild cognitive impairment 7 (20%) 18 (17%) 25 Dementia 1 (3%) 3 (3%) 4 Reduced AD signature cortical thickness 20 (57%) 60 (58%) 138 0.91 Elevated β-amyloid 4 (33%) 11 (31%) 47 0.90 FDG PET SUVR 1.52 (0.16) 1.59 (0.18) 45 0.46 White matter hyperintensity volume % of TIV 1.12 (0.57) 0.76 (0.69) 49 0.011 With cortical infarctions 4 (24%) 1 (3%) 55 0.013 N (%) unless otherwise stated; * Kruskal-Wallis rank sum or Pearson’s Chi-squared test. SD=standard deviation; AD= Alzheimer’s disease; SUVR=standardized uptake value ratio; TIV= Total intracranial volume. Conclusion: Our preliminary data suggest significant differences in cerebrovascular biomarker measures by RA status. Further studies would add valuable information to our understanding and insight into the development of interventions for the prevention of cerebrovascular pathology in RA patients. References: [1]Dregan, A., P. Chowienczyk and M. C. Gulliford (2015). “Are Inflammation and Related Therapy Associated with All-Cause Dementia in a Primary Care Population?” J Alzheimers Dis 46(4): 1039-1047. Acknowledgements: The study was supported by the NIH AG068192. The Mayo Clinic Study of Aging was supported by the NIH (U01 AG006786, P50 AG016574, R01AG057708, R01 AG011378, R01 AG021927, R01 AG041851, R01 NS097495), the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic, Mayo Foundation for Medical Education and Research, the Liston Award, the Schuler Foundation and was made possible by the Rochester Epidemiology Project (R01 AG034676). Disclosure of Interests: Maria Vassilaki Shareholder of: M. Vassilaki has equity ownership in Abbott Laboratories, Johnson and Johnson, Medronic and Amgen., Grant/research support from: M. Vassilaki has received research funding from Roche and Biogen in the past., Cynthia S. Crowson: None declared, John M Davis III Grant/research support from: JM. Davis III receives research funding from Pfizer., Stephanie Duong: None declared, David Jones: None declared, Michelle Mielke Consultant of: M. Mielke has consulted for Biogen and Brain Protection Company, Prashanthi Vemuri: None declared, Elena Myasoedova: None declared