Effects of Systemic Lupus Erythematosus on the Brain: A Systematic Review of Structural MRI Findings and their Relationships with Cognitive Dysfunction

Background: Cognitive dysfunction (CD) is highly prevalent in systemic lupus erythematosus (SLE), yet the underlying mechanisms are poorly understood. Neuroimaging utilizing advanced magnetic resonance imaging (MRI) metrics may yield mechanistic insights. We conducted a systematic review of neuroimaging studies to investigate the relationship between structural and diffusion MRI metrics and CD in SLE. Methods: We systematically searched several databases between January 2000 and October 2023 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Retrospective, and prospective studies were screened for search criteria keywords (including structural or diffusion MRI, cognitive function, and SLE) to identify peer-reviewed articles reporting advanced structural MRI metrics and evaluating CD in human patients with SLE. Results: Eighteen studies (8 structural MRI, 9 diffusion MRI, and 1 with both modalities) were included; sample sizes ranged from 11 to 120 participants with SLE. Neurocognitive assessments and neuroimaging techniques, parameters, and processing differed across articles. The most frequently affected cognitive domains were memory, psychomotor speed, and attention; while abnormal structural and/or diffusion MRI metrics were found more consistently in the hippocampus, corpus callosum, and frontal cortex of patients with SLE, with and without clinically diagnosed CNS involvement. Conclusion: Advanced structural MRI analysis can identify total and regional brain abnormalities associated with CD in patients with SLE, with potential to enhance clinical assessment. Future collaborative, longitudinal studies of neuroimaging in SLE are needed to better characterize CD, with focus on harmonized neurocognitive assessments, neuroimaging acquisitions and post-processing analyses, and improved clinical characterization of SLE cohorts. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Funding for this project included a Lupus Foundation of America Career Development Award (to Dr. El Tal), Lupus Research Alliance Administrative Supplement to Promote Diversity in Lupus Research (to Santiago Arciniegas), Canada Research Chair Tier 2 in Mental Health and Chronic Disease of Childhood (to Dr. Knight), and Lupus Research Alliance Career Development Award to Promote Diversity in Lupus Research (to Dr. Knight). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study did not use any human or animal data. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript.