The following article is a part of conference coverage from the American College of Rheumatology (ACR) Convergence 2021, being held virtually from November 3 to 10, 2021. The team at Rheumatology Advisor will be reporting on the latest news and research conducted by leading experts in rheumatology. Check back for more from the ACR Convergence 2021.


Patients with systemic lupus erythematosus (SLE) and cognitive impairment (CI) have distinct differences in brain functional connectivity compared with patients with SLE without CI and healthy control participants, according to study results presented at the American College of Rheumatology (ACR) Convergence 2021, held virtually from November 3 to 10, 2021.

Cognitive impairment is the most common manifestation of neuropsychiatric SLE; however, its underlying mechanisms remain poorly understood.

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In the current study, the researchers sought to explore the associations between enhanced permeability of the blood-brain barrier (BBB), loss of grey matter volume, and CI in patients with SLE. Non-task-based functional connectivity between regions of the brain were examined using resting state functional magnetic resonance imaging (rsfMRI).

A total of 78 adult patients with SLE (49.4±14.3 years; 89.7% women) and 71 healthy control participants (38.9±12.9 years; 69.0% women) were enrolled in the study from a single academic medical center in Halifax, Nova Scotia, Canada. Global cognitive function and performance in 5 different domains were evaluated using standard neuropsychologic tests. Dynamic contrast-enhanced MRI was used to measure BBB permeability.

All participants underwent rsfMRI, in which blood oxygen level-dependent (BOLD) signals were obtained to exhibit neural activation. To analyze the resting-state functional connectivity (rsFC) between brain regions, mean BOLD signals were obtained from 131 regions across 5 canonic resting-state brain networks. All rsFC values were then compared among patients with SLE and CI, patients with SLE without CI, and healthy control participants, as well as among patients with SLE with extensive BBB permeability, patients with SLE without extensive BBB permeability, and healthy control participants.

Overall, 51 connections between functional brain regions were shown to differ significantly between patients with SLE with and without CI (P <.05). According to multivariate analysis of variance, significant differences were observed between patients with SLE with CI and healthy control participants (P =.006). The mean functional connectivity of affected regions differed between patients with SLE with normal BBB permeability and patients with SLE with extensive BBB leakage (P =.025).

In addition, patients with SLE with CI and those with SLE with extensive BBB leakage had more positive functional connections compared with those in the other groups. Further, the total number of brain-wide connections of specific brain regions decreased with greater BBB permeability (P =.011) and were significantly lower among patients with SLE with CI than in those with SLE without CI (P =.01).

The researchers concluded that study findings implied an association between BBB leakage and neural pathology that underlies CI in patients with neuropsychiatric SLE.


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Hanly J, Robertson J, Kamintsky L, et al. Functional connectivity, enhanced blood-brain barrier leakage and cognitive impairment in systemic lupus erythematosus. Presented at: ACR Convergence 2021; November 3-10, 2021. Abstract 0456.