1.Scientific Rationale:
Sjögren’s Syndrome (SS) is a systemic autoimmune disease characterized by pervasive chronic inflammation. While its glandular effects are well-known, its impact on the central nervous system-specifically brain white matter (WM)-is increasingly recognized but lacks large-scale validation. Patients frequently report “brain fog” and cognitive symptoms, which may be linked to white matter hyperintensities (WMH) and microstructural integrity loss. However, it remains unclear whether these changes are a direct result of autoimmune-driven inflammation or secondary to vascular comorbidities. By leveraging UK Biobank’s multimodal MRI data (T2-FLAIR and DTI), blood-based inflammatory markers (CRP and leukocyte profiles), and standardized cognitive batteries, this study aims to decipher the “neuro-inflammatory axis” in SS. This large-scale analysis is essential to identify early neuroimaging biomarkers for cognitive impairment in autoimmune populations.
2.Research Questions
!1!Do individuals with Sjögren’s Syndrome exhibit a higher burden of white matter hyperintensities and impaired microstructural integrity compared to age- and sex-matched controls?
!2!To what extent do systemic inflammatory markers (e.g., CRP, Neutrophil-to-Lymphocyte Ratio) correlate with the severity of white matter damage in these patients?
!3!Does the alteration in white matter structure mediate the relationship between systemic inflammation and cognitive performance (e.g., processing speed and executive function)
3.Objectives:
!1!To quantify and compare white matter lesion volumes and DTI-derived metrics (FA, MD) between SS patients and healthy controls using propensity score matching.
!2!To evaluate the association between blood-based inflammatory biomarkers and neuroimaging phenotypes of white matter integrity.
!3!To perform mediation analysis to determine if white matter disruption acts as a biological bridge between systemic inflammation and cognitive decline.
