Fatigue and cognitive function in systemic lupus erythematosus: associations with white matter microstructural damage. A diffusion tensor MRI study and meta-analysis.
Objective The objective of this study was to investigate fatigue and cognitive impairments in systemic lupus erythematous (SLE) in relation to diffuse white matter microstructural brain damage. Methods Diffusion tensor MRI, used to generate biomarkers of brain white matter microstructural integrity, was obtained in patients with SLE and age-matched controls. Fatigue and cognitive function were assessed and related to SLE activity, clinical data and plasma biomarkers of inflammation and endothelial dysfunction. Results Fifty-one patients with SLE (mean age 48.8 ± 14.3 years) were included. Mean diffusivity (MD) was significantly higher in all white matter fibre tracts in SLE patients versus age-matched healthy controls ( p < 0.0001). Fatigue in SLE was higher than a normal reference range ( p < 0.0001) and associated with lower MD ( ß = -0.61, p = 0.02), depression ( ß = 0.17, p = 0.001), anxiety ( ß = 0.13, p = 0.006) and higher body mass index ( ß = 0.10, p = 0.004) in adjusted analyses. Poorer cognitive function was associated with longer SLE disease duration ( p = 0.003) and higher MD ( p = 0.03) and, in adjusted analysis, higher levels of IL-6 ( ß = -0.15, p = 0.02) but not with MD. Meta-analysis (10 studies, n = 261, including the present study) confirmed that patients with SLE have higher MD than controls. Conclusion Patients with SLE have more microstructural brain white matter damage for age than the general population, but this does not explain increased fatigue or lower cognition in SLE. The association between raised IL-6 and worse current cognitive function in SLE should be explored in larger datasets.
1 Centre for Clinical Brain Sciences, University of Edinburgh, UK.
S J
SJ
Wiseman
1 Centre for Clinical Brain Sciences, University of Edinburgh, UK.
M E
ME
Bastin
1 Centre for Clinical Brain Sciences, University of Edinburgh, UK.
I F
IF
Hamilton
1 Centre for Clinical Brain Sciences, University of Edinburgh, UK.
D
D
Hunt
2 Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, UK.|3 Department of Psychology, University of Edinburgh, UK.
S J
SJ
Ritchie
4 Department of Rheumatology, Western General Hospital, Edinburgh, UK.
E N
EN
Amft
5 Division of Cardiovascular and Diabetes Medicine, University of Dundee, UK.
S
S
Thomson
5 Division of Cardiovascular and Diabetes Medicine, University of Dundee, UK.
J F F
JF
Belch
6 Centre for Genomic and Experimental Medicine, University of Edinburgh, UK.
S H
SH
Ralston
1 Centre for Clinical Brain Sciences, University of Edinburgh, UK.
J M
JM
Wardlaw
D000328:Adult; D000368:Aged; D003072:Cognition Disorders / Q000000981:diagnostic imaging*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005221:Fatigue / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000000981:diagnostic imaging / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D066127:White Matter / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
C508600:IL6 protein, human; D015850:Interleukin-6
Autoimmune diseases; cytokines; inflammation; systemic lupus erythematosus
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