Altered cognitive function in systemic lupus erythematosus and associations with inflammation and functional and structural brain changes

Objectives Cognitive dysfunction (CD) is common in systemic lupus erythematosus (SLE) but the cause remains unclear and treatment options are limited. We aimed to compare cognitive function in SLE and healthy controls (HCs) using both behavioural and neuroimaging techniques. Methods SLE patients with stable disease and HCs were recruited. Clinical and psychological data were collected along with a blood sample for relevant biomarkers. Neurocognitive function was assessed using tests from the CANTAB® and functional magnetic resonance imaging (fMRI) was used to examine brain responses to working memory (WM) and emotional processing (FERT) tasks. Results Compared to HCs (n=30), SLE patients (n=36) scored higher on measures of depression, fatigue and had higher hsCRP (p=0.013), IL-6 (p=0.003) and BLyS (p<0.001). SLE patients had poorer performance on a task of sustained attention (p=0.002) and had altered brain responses, particularly in default mode network (DMN) regions and the caudate, during the WM task. Higher organ damage and higher VCAM-1 were associated with less attenuation of the DMN (p=0.005 and p=0.01 respectively) and lower BOLD signal in the caudate areas (p=0.005 and p=0.001 respectively). Increased IL-6 was also associated with lower BOLD signal in caudate areas (p=0.032). Conclusions Sustained attention was impaired in SLE patients. Poor attenuation of the DMN may contribute to cognitive impairments in SLE and our data suggests that in addition to mood and fatigue inflammatory mechanisms and organ damage impact cognitive functioning in SLE. The multifaceted nature of CD in SLE means any therapeutic interventions should be individually tailored.