Fatigue and cognitive function in systemic lupus erythematosus: associations with white matter microstructural damage. A diffusion tensor MRI study and meta-analysis

Abstract

Objective 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 (β = −0.61, p=0.02), depression (β = 0.17, p=0.001), anxiety (β = 0.13, p=0.006) and higher body mass index (β = 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 (β = −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.

Metabolic and microstructural alterations in the SLE brain correlate with cognitive impairment

“…Additional longitudinal studies are needed to verify this prediction. While several studies have reported WM alterations in NPSLE compared with HC subjects in segments of the CC, the forceps, anterior corona radiata, thalamus, and parietal and frontal lobes (33-36) and overall diminished volume of the CC (34, 37), our results support the growing body of literature demonstrating significant WM abnormalities in SLE subjects without acute neuropsychiatric manifestations (38)(39)(40)(41)(42). Most of these studies in SLE subjects without neuropsychiatric manifestations failed to demonstrate significant correlations between diminished WM integrity and cognition.…”

Altered cognitive function in systemic lupus erythematosus and associations with inflammation and functional and structural brain changes

“…Previous studies have found patients with SLE to have a greater number and larger PVS in the basal ganglia which did not reach significance in our study; we did however find differences between the HC and SLE in PVS in the centrum semiovale. PVS is an imaging marker for cerebral small vessel disease;26 27 however, we did not find any correlations between several serological markers of vascular disease (LAC, aCL antibodies and VCAM-1) and CSO-VRS, although we did exclude patients with severe vascular disease.…”

Fatigue of systemic lupus erythematosus in China: contributors and effects on the quality of life

“…Studies indicate that fatigue in SLE is associated with anxiety, depression, pain and body mass index (BMI). 8 , 9 The correlation between fatigue scoring and depression is higher in the SLE population than other medical conditions such as Lyme disease or multiple sclerosis. 10 , 11 Jump et al 12 find the importance of pain in predicting fatigue levels in SLE patients.…”