Factors Associated With Altered Cognitive Function in SLE

Systemic lupus erythematosus-specific factors (eg, inflammation, disease damage/duration) are associated with cognitive dysfunction, as well as chronic disease factors (eg, fatigue, depression, pain, medication).

In addition to mood and fatigue, inflammatory mechanisms and organ damage have an impact on cognitive functioning in systemic lupus erythematosus (SLE), according to study results published in the Annals of the Rheumatic Diseases.

In this exploratory study, patients with SLE were recruited from the rheumatology department at Manchester University NHS Foundation Trust Hospitals in the United Kingdom, and healthy controls were recruited via the study participants. The investigators sought to compare cognitive function in patients with SLE and healthy controls with the use of both behavioral and neuroimaging techniques. They gathered clinical and psychological data and obtained blood samples for relevant biomarkers from all participants. Neurocognitive function was evaluated with the use of tests from the Cambridge Neuropsychological Test Automated Battery. Functional magnetic resonance imaging (fMRI) was utilized to assess brain responses to working memory (WM) and emotional processing (facial emotional recognition) tasks.

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A total of 36 patients with SLE and 30 healthy controls were evaluated. Patients with SLE scored higher on measures of depression and fatigue. Moreover, participants with SLE had significantly greater high-sensitivity C-reactive protein levels (P =.013), higher interleukin (IL)-6 levels (P =.003), and higher B-lymphocyte stimulator levels (P <.001) compared with controls.

The SLE arm performed significantly worse on the rapid information visual processing task, a measure of sustained attention, compared with the control arm (P =.002). In addition, during the WM task, patients in the SLE group exhibited altered brain responses, especially in default mode network (DMN) regions and the caudate. Higher vascular cell adhesion molecule-1 (VCAM-1) and organ damage were both significantly associated with less attenuation of the DMN (P =.01 and P =.005, respectively), as well as lower BOLD signal in the caudate areas (P =.001 and P =.005, respectively). Increased levels of IL-6 were also significantly associated with lower BOLD signal in the caudate areas (P =.032).

The investigators concluded that in patients with SLE, compared with healthy controls, sustained attention was impaired. “Poor attenuation of the DMN may contribute to [cognitive dysfunction] in SLE, although prospective studies may be needed to confirm this,” they noted. Cognitive dysfunction in SLE has multiple drivers and “therapeutic approaches will need to be individually tailored to address the relevant drivers in individual patients.”

Disclosure: This study was partially funded by an unrestricted grant from Sanofi Genzyme.


Barraclough M, McKie S, Parker B, et al. Altered cognitive function in systemic lupus erythematosus and associations with inflammation and functional and structural brain changes [published online April 12, 2019]. Ann Rheum Dis. doi:10.1136/annrheumdis-2018-214677