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Abstract Number: 1941

Altered Cognitive Function in Systemic Lupus Erythematosus and Associations with Inflammation and Functional Brain Changes

Michelle Barraclough1,2, Rebecca Elliott2,3, Benjamin Parker4,5, Shane McKie2,3, Alan Jackson6, Philip Pemberton7 and Ian N. Bruce2,4, 1The University of Manchester, Arthritis Research UK Centre for Epidemiology, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester, United Kingdom, 2NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom, 3The University of Manchester, Division of Neuroscience & Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester, United Kingdom, 4Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester, United Kingdom, 5NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, United Kingdom, 6Imaging Sciences, Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, United Kingdom, 7Department of Clinical Biochemistry, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester, United Kingdom

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Cognitive dysfunction, fMRI and systemic lupus erythematosus (SLE)

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Session Information

Date: Monday, October 22, 2018

Session Title: 4M107 ACR Abstract: SLE–Clinical II: Renal & Neuropsychiatric Disease in SLE (1941–1945)

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

<>Background/Purpose:

Cognitive dysfunction is a common problem in systemic lupus erythematosus (SLE) but the cause is still unclear; measuring it can be difficult and, as such, treatment options are limited. We examined cognitive function (CF) in a stable SLE group using both behavioural and imaging techniques. Associations for cognitive dysfunction in SLE were also explored.

  <>Methods: 36 stable SLE (SLE 1997 ACR Criteria) and 30 healthy controls (HC) were recruited. Demographics clinical features, psychological questionnaires and blood samples were collected. We compared periventricular hyperintensities (PVH), deep white matter hyperintensities (DWMH), brainstem and basal ganglia features.  CF was assessed using selected tests from the CANTAB®, and fMRI was used to examine blood-oxygen-level dependent (BOLD) responses to a working memory and attention task (n-back) and a facial emotional processing task (FERT). The fMRI data was modelled using SPM12. All other data was analysed using SPSS 22.   <>Results:

SLE patients had significantly higher scores for depression and fatigue and they also had higher levels of IL-6, high sensitivity CRP, VCAM-1 and BlyS (Table 1). The SLE group performed significantly worse on a behavioural task of sustained attention (p=0.002) but similarly on all other cognitive tasks. They had more and larger perivascular spaces (PVS) in the centrum semiovale (CSO-VRS), χ2=15.50, p<0.001, compared to the HC group. We also found altered BOLD signals compared to the HC group for the n-back task in regions associated with the default mode network during the working memory condition and in the lingual gyrus during the attention condition. For the FERT task, during the sadness condition, differences were also found   (Figure 1). The attenuated BOLD signal in the right superior temporal gyrus positively correlated with VCAM-1 (r=0.53, p=0.01), and SLICC/ACR-DI score (rs=0.56, p=0.005). The attenuated BOLD signal in the lingual gyrus positively correlated with the BILAG total score (rs=0.45, p=0.033) and IL-6 (rs=0.44, p=0.036).

 

Table 1: Differences between the SLE and HC groups for demographic, psychiatric and fatigue characteristics and serological inflammatory markers
Variable SLE (n=36) HC (n=30) p-value
  Mean (S.D.), Median (LQ, UQ) or n (%)  
Demographic
Age (years) 40 (32, 48.75) 32 (27, 46.5)  p=0.14
Gender (% female) 34 (94) 30 (100) p=0.19
Handedness (% right-handed) 30 (83) 28 (93) p=0.34
Years in education 16.11 (3.51) 17.97 (3.40) p=0.034
WTAR (IQ) 102.5 (98.25, 108) 111 (105, 114) p=0.001
Depression
MADRS 4 (1, 8) 1 (0, 3) p=0.012
HADS – D 4 (1, 9) 1 (0, 2) p<0.001
BDI – II 10 (4, 20.25) 3 (0.75, 8) p=0.002
Anxiety
HADS – A 6 (3, 10.5) 5 (2, 7) p=0.08
Fatigue
FSMC – Motor score 36 (22, 40.5) 14 (11.5, 18.5) p<0.001
FSMC – Cognitive score 31 (22, 40) 14 (11.5, 18.5) p<0.001
FSMC – total score 67.5 (44.75, 80.5) 27 (23, 37) p<0.001
Biomarkers of inflammation and endothelial activation
hsCRP (mg/l) 1.44 (0.66, 5.06) 0.88 (0.39, 1.39) p=0.013
IL-6 (pg/ml) 1.67 (0.50, 5.33) 0.50 (0.50, 1.32) p=0.003
VCAM-1 (ng/ml) 474.93 (194.30) 345.66 (53.79) p=0.001
VEGF (pg/ml) 66.04 (13.93, 139.60) 45.42 (6.04, 114.93) p=0.275
BLyS (ng/ml) 0.51 (0.35, 0.71) 0.34 (0.27, 0.39) p<0.001
WTAR: Weschler Test of Adult Reading; MADRS: Montgomery Asberg Depression Rating Scale; HADS-D: Hospital Anxiety and Depression Scale – Depression score; BDI-II: Becks Depression Inventory – II; HADS-A: Hospital Anxiety and Depression Scale – Anxiety score; FSMC: Fatigue Scale for Motor and Cognitive Functions; hsCRP: High Sensitivity C-Reactive Protein; IL-6: Interleukin 6; VCAM-1: Vascular cell adhesion molecule-1; VEGF: Vascular Endothelial Growth Factor; BLyS: B lymphocyte stimulator
                                               
<>Conclusion:

Structural and functional changes related to cognition in SLE may, in part, be influenced by inflammation and aspects of disease including pre-existing damage. Also, the compensatory brain mechanisms used by the SLE group to maintain adequate CF may make SLE patients more susceptible to emotional interference during non-emotional cognitive tasks. Whilst multifactorial in nature, certain aspects of SLE CF may be sensitive to changes in disease status and thus to targeted therapeutic interventions.


Disclosure: M. Barraclough, Sanofi Genzyme, 2; R. Elliott, None; B. Parker, None; S. McKie, None; A. Jackson, None; P. Pemberton, None; I. N. Bruce, Sanofi Genzyme, 2.

To cite this abstract in AMA style:

Barraclough M, Elliott R, Parker B, McKie S, Jackson A, Pemberton P, Bruce IN. Altered Cognitive Function in Systemic Lupus Erythematosus and Associations with Inflammation and Functional Brain Changes [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/altered-cognitive-function-in-systemic-lupus-erythematosus-and-associations-with-inflammation-and-functional-brain-changes/. Accessed January 30, 2023.
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