Background/Purpose: Factors associated with neuropsychiatric damage in SLE has been described. Yet, determinants of progression of small vessel related brain injury, and major neurocognitive disorder-vascular dementia (MCD) is not well understood. The purpose of this study is a case-control analysis that compare neuropsychiatric lupus (NPSLE) patients with MCD and those who have not developed MCD.

Methods: A nested case-control study of 24 NPSLE subjects with MCD out of the SLE cohort at the University of Maryland between 1995 and 2018, were identified according to the 2007 American College of Rheumatology proposed response criteria for severe neurocognitive impairment in SLE (> 2.0 SD below the mean compared to normative data) that interferes with daily functioning leading to loss of independence. For each NPSLE patient with MCD, 3 age- and gender- matched NPSLE subjects with no MCD were randomly selected from the same cohort, and assigned an index date of the NP events corresponding to the MCD group (n= 72).

Results: 24 NPSLE cases with MCD [mean age 48.8 +/- 18.5 years, African American (71.0 %), mean level of education 11.7 years, mean SLE duration of 15 years] were compared to 72 NPSLE patients with no MCD [mean age 44.8 +/- 17.1 years, African American (69.4 %), mean level of education 12.3 years, mean SLE duration of 13 years]. Baseline data including, severity of NPSLE events, structural neuroimaging findings of cortical and subcortical infarcts, hypoperfusion with watershed infarction, periventricular white matter hyperintensity, cardiovascular disease risk factors and Framingham risk score, cytotoxic or immune therapy, glucocorticoid, anticoagulation or aspirin use were not significantly different among both groups. Similarly, autoantibodies of phospholipid, ribosomal-P, anti-neuronal antibodies, NR2 and NMDA, were similar among both groups. Higher disease activity, glomerulonephritis and depression were more frequent among MCD group than in comparators. Independent predictors of MCD included baseline lacunar infracts based in the caudate, thalamus, cerebellum, and peri-Sylvian regions (OR 5.0, 95%CI: 1.2-20.3, P < 0.012), regional volume loss (OR 20.0, 95% CI: 2.2-182.4, P < 0.001), and cerebral atrophy (OR 1.8, 95% CI: 1.2-2.7, P < 0.001).

Medication non-adherence for SLE disease activity (OR 2.0, 95% CI: 1.1- 3.9, p < 0.012), uncontrolled dyslipidemia (OR 16.3, 95% CI: 2.9-91.8, P < 0.001), uncontrolled hypertension (OR 7.3, 95 % CI: 1.6-33.1, P < 0.003), and alcoholism (OR 4.4, 95% CI: 0.9-25.2, p < 0.076) were independent predictors of MCD progression. Hydroxychloroquine use was associated with slow progression of MCD (OR 3.0, 95% 1.4-6.7, P < 0.001).

Conclusion: Despite a similar prevalence of vascular risk factors at baseline, the risk of MCD is higher in NPSLE patients who do not adhere to medications related to SLE and control of cardiovascular risk factors than in matched comparable group. Understanding the complexity of medication non adherence in SLE need to be identified, and patient-tailored interventions focusing on patients’ specific barriers to adherence are needed. This observation deserve further study to confirm the use of hydroxychloroquine as an intervention to slow progression of MCD.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/determinants-of-major-neurocognitive-disorder-vascular-dementia-in-sle-the-importance-of-treatment-adherence-of-sle-disease-activity-and-cardiovascular-risk-factors/