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Biomarkers
302 Resting state functional connectivity in SLE patients and association with cognitive impairment and blood-brain barrier permeability
  1. John G Hanly1,
  2. Jason W Robertson2,
  3. Alexandra Legge3,
  4. Lyna Kamintsky4,
  5. Guillermo Aristi2,
  6. Alon Friedman4,5,
  7. Steven D Beyea6,
  8. John D Fisk7,
  9. Antonina Omisade8,
  10. Cynthia Calkin9,
  11. Tim Bardouille10,
  12. Chris Bowen6,
  13. Kara Matheson11 and
  14. Javeria A Hashmi2
  1. 1Division of Rheumatology, Department of Medicine and Department of Pathology, Queen Elizabeth II Health Sciences Center and Dalhousie University, Halifax, Nova Scotia, Canada
  2. 2Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Nova Scotia Health Authority, Halifax, Nova Scotia, Canada
  3. 3Division of Rheumatology, Department of Medicine, Queen Elizabeth II Health Sciences Center and Dalhousie University, Halifax, Nova Scotia, Canada
  4. 4Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada
  5. 5Departments of Cognitive and Brain Sciences, Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer Sheva, Israel
  6. 6Biomedical Translational Imaging Centre (BIOTIC), QEII Health Sciences Centre, and Department of Diagnostic Radiology, Dalhousie University, Halifax, Nova Scotia, Canada
  7. 7Nova Scotia Health Authority, Halifax, Canada and the Departments of Psychiatry, Psychology and Neuroscience and Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
  8. 8Acquired Brain Injury (Epilepsy Program), Nova Scotia Health Authority, Halifax Nova Scotia, Canada
  9. 9Department of Psychiatry and Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada
  10. 10Department of Physics, Dalhousie University, Halifax, Nova Scotia, Canada
  11. 11Research Methods Unit, Nova Scotia Health Authority, Halifax, Nova Scotia, Canada

Abstract

Objective Cognitive impairment (CI) is the most frequent manifestation of neuropsychiatric systemic lupus erythematosus (NPSLE), yet the mechanisms underlying it remain poorly understood. We have previously reported an association between enhanced permeability of the blood-brain barrier (BBB), loss of grey matter volume and cognitive impairment in SLE patients. This study examined the associations of brain functional connectivity (FC) with CI and BBB dysfunction among patients with SLE.

Methods Cognitive function was assessed by neuropsychological testing (n=77). Resting-state FC (rsFC) between brain regions, measured by functional MRI (n=78), assessed coordinated neural activation in 131 regions across five canonical brain networks. BBB permeability was measured by dynamic contrast-enhanced MRI (DCE-MRI) (n=61). Differences in rsFC were compared between SLE patients with CI (SLE-CI) and those with normal cognition (SLE-NC), between SLE patients with and without extensive BBB leakage, and with healthy controls.

Results A whole-brain rsFC comparison found significant differences in intra-network and inter- network FC in SLE-CI versus SLE-NC patients. The affected connections showed a reduced negative rsFC in SLE-CI compared to SLE-NC and healthy controls. Similarly, a reduced number of brain-wide connections was found in SLE-CI patients compared to SLE-NC (P=0.030) and healthy controls (P=0.006). Specific brain regions had a lower total number of brain-wide connections in association with extensive BBB leakage (P=0.011). Causal mediation analysis revealed that 64% of the association between BBB leakage and CI in SLE patients was mediated by alterations in FC.

Conclusion SLE patients with CI had abnormalities in brain rsFC which accounted for most of the association between extensive BBB leakage and CI.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/lupus-2023-lupus21century.15

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