Multifactorial nature of cognitive dysfunction highlighted in SLE
medwireNews: Poor attenuation of the default mode network (DMN) regions of the brain may contribute to cognitive impairments in patients with systemic lupus erythematosus (SLE), say UK researchers.
The team, led by Ian Bruce from the University of Manchester, also showed that individuals with SLE have reduced levels of sustained attention compared with healthy controls and that inflammation and organ damage may impact cognitive functioning in these patients.
The researchers used both behavioral and neuroimaging techniques to compare cognitive function in 36 patients with SLE and 30 healthy controls.
The Cambridge Neuropsychological Test Automated Battery showed that patients with SLE had significantly lower scores in tests of sustained attention and emotional processing than healthy controls but were no different from controls in measures of visual, verbal, or working memory, or executive function.
The SLE group also had significantly higher levels of inflammatory biomarkers, fatigue, and depression, even though patients with major depression were excluded from the study.
On structural magnetic resonance imaging (MRI), 43% of the SLE group had increases in the perivascular spaces of the centrum semiovale, whereas none of the control group did, while functional MRI showed that patients with SLE performed worse than controls on measures of attention and working memory.
For example, during the working memory task, people in the SLE group had a more significant decrease in blood oxygenation level-dependent (BOLD) signal in the cognitive (caudate) regions of the brain, whereas the signal decrease was greater in the control group for the DMN regions (left transverse and right superior temporal gyrus).
“The limited ability to reduce BOLD signals in the DMN regions of the SLE patients implies an inability to inhibit self-reflective processes which can impede performance on cognitive tasks that do not usually have an emotional component, by allowing emotional interference from self-reflection and worries about task performance,” Bruce and co-authors remark in the Annals of the Rheumatic Diseases.
They add that they observed a greater functional MRI response in frontal regions of the brain in the SLE versus control groups when viewing sad faces, which supports this hypothesis. Furthermore “[s]uch increased responses to sad expressions is also associated with depression,” the team notes.
Exploratory analyses showed that organ damage, assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, vascular cell adhesion molecule-1 levels, and current use of biologic medication were all positively correlated with a higher BOLD signal in the DMN regions of the brain and with a lower signal in caudate regions. There was also a negative correlation between interleukin-6 levels and BOLD signal in the right and left caudate.
Bruce et al conclude that their study highlights “the multifaceted nature of [cognitive dysfunction] in SLE and that future therapeutic approaches will need to be individually tailored to address the relevant drivers in individual patients.”
By Laura Cowen
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