Background Cognitive dysfunction (CD) affects up to 90% of systemic lupus erythematosus (SLE) patients and significantly impacts patient quality of life. The cause is multifaceted with many factors common across chronic diseases. It is thus difficult to ascertain the direct impact active disease in SLE has upon immediate cognitive function.
Objectives The aim of this study was to investigate the effects of active disease in SLE on CD. We compared cognitive measures in SLE patients with stable disease activity (SLE-S) to those with active disease (SLE-F).
Methods 34 SLE-S and 24 SLE-F were recruited, all meeting 1997 ACR criteria. Active disease was defined as BILAG A or B with a change in treatment. Stable disease was defined as SLEDAI-2K ≤4. Overall 14/24 SLE-F patients were assessed again at 2nd visit (v1 vs v2) when their disease activity had reduced. CD was measured using tests from a computerized battery of tests (CANTAB®). fMRI was used to examine neuronal responses to a working memory and attention task (n-back) and a facial emotional processing task (FERT). Analysis compared the SLE-S and SLE-F groups as well as a within group comparison for v1 vs v2. fMRI data were analysed using SPM12. All other data were analysed using SPSS 22.
Results There were no differences between the SLE-S and SLE-F groups or between v1 and v2 on demographic and clinical measures except disease activity. The SLE-F group scored higher than the SLE-S group on the MADRS depression scale (p=0.003) but no other significant differences in psychiatric symptoms were observed. There were no significant differences on the CANTAB® for either comparison (table 1). The fMRI showed a SLE-S vs SLE-F difference in n-back related response in the medial prefrontal cortex (p=0.012; figure 1). No v1 vs v2 differences were found, nor for either comparison for the FERT.
Conclusion In a cohort well matched on confounding factors these results suggest that active disease does not impair cognitive function. However, the differences in the medial frontal cluster during the working memory task may indicate the use of compensatory mechanisms to maintain cognitive function as has been found elsewhere. Alternatively, as this is a default mode network region, often implicated in self-reflective processes it may be that CD is more directly associated with differences in mood. As such when treating SLE patients with self-reported CD it is important to consider factors other than disease activity.
Acknowledgement This study was partially funded by an unrestricted grant from Sanofi Genzyme and supported by the NIHR Manchester Biomedical Research Centre.
Disclosure of Interests Michelle Barraclough Grant/research support from: This study was partially funded by an unrestricted grant from Sanofi Genzyme., Rebecca Elliott: None declared, Shane McKie: None declared, Ben Parker Grant/research support from: GSK, Consultant for: AZ, UCB, GSK, Ian N. Bruce Grant/research support from: Genzyme Sanofi, GlaxoSmithKline, Consultant for: AstraZeneca, Eli Lilly, GlaxoSmithKline, ILTOO Pharma, MedImmune, Merck Serono, Speakers bureau: GlaxoSmithKline, UCB Pharma
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