Background/Purpose: SLE patients are at high risk for accumulation of white matter hyperintensity (WMH) on brain MRI which has been correlated with cognitive impairment. Our goal is to determine whether the progression of WMH in newly diagnosed SLE patients predicts increased risk of cognitive impairment.

Methods: Brain MR T2 weighted images were compared at baseline and annually for 5 years among newly diagnosed SLE patients, presenting with neuropsychiatric SLE (NPSLE), {(n= 30), [ mean age 37.6 years, 73 % African American, and 90 % women]},  and age- and gender- matched non NPSLE patients (n= 25), and  healthy controls (n=20) to assess WMH burden (mild, moderate or severe). Standard cognitive tests were examined at enrollment and at end of study. Demographic and clinical manifestations were compared among the groups. Significant variables in the analyses, depression, cardiovascular risk factors and worsening of WMH grade using dichotomous measures were entered into multivariable and Cox proportional hazard analyses to determine their contribution to cognitive impairment.

Results: At baseline, 59 MRI were normal and16 had WMH lesions (NPSLE = 9, non NPSLE= 4 and controls = 3). The WMH burden was higher among NPSLE patients compared to non NPSLE patients (OR= 3.1, 95 % CI: 0.7- 13.2, p value =0.09). At baseline, frontal and parieto -occipital lesions were more frequent among NPSLE patients, whereas periventricular lesions were more frequent among non NPSLE patients or controls. At end of study, 24 patients had normal MRI findings and 21 had new and increased WMH lesions (NPSLE =13, non NPSLE =6, control= 2). The rate of WMH burden progression was variable across the groups. NP SLE patients had a faster rate of accumulation of WMH lesions, as compared to non NPSLE (OR =3.5, 95 % CI: 1.1-10.7; p value= 0.03). The median number of impaired cognitive domains increased, regardless of the presence of baseline WMH lesions particularly among NPSLE compared to non NPSLE or controls.

Ischemic strokes and MRI -defined incident infarcts (OR = 5.8; 95% CI = 1.2–29.4; p value = 0.04), and worsened WMH grade (OR = 4.3; 95% CI = 2.1–16.3; p value = 0.03), were associated with increased risk of cognitive impairment in the areas of attention, processing speed and executive function.  Hydroxychloroquine use was associated with reduced risk for WMH progression (OR= 0.3, 95 % CI: 0.1- 0.7; p value= 0.02), but not cognitive impairment.

Conclusion: The progression of WMH has prognostic relevance for long-term cognitive outcome in newly diagnosed SLE. Strategic preventive measures are needed to optimally target individuals at highest risk of cognitive decline.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-progression-of-brain-mri-biomarker-of-cognitive-impairment-white-matter-hyperintensity-in-systemic-lupus-a-clinical-and-imaging-longitudinal-study/