Regular aspirin use is associated with improved cognitive function in older patients with systemic lupus erythematosus (SLE) in conjunction with the presence of other vascular risk factors. Regular prednisone use is associated with decreased cognitive functioning in middle-aged patients with SLE. Although this prednisone effect was independent of measures of SLE-associated disease activity, the authors cannot exclude the possibility that consistent prednisone use is a surrogate for more severe disease.

The prevalence of NPSLE was high in this cohort of unselected patients with SLE. Headaches, cognitive dysfunction, and psychiatric disorders were the most common NPSLE syndromes seen. These results will be easily comparable to other studies also using standardized diagnostic criteria. However, the lack of ethnicity and language-matched normative neuropsychological data may make comparisons of cognitive dysfunction in SLE populations difficult.

Objective Lacunar strokes are a leading cause of cognitive impairment and vascular dementia. However, adequate characterization of cognitive impairment is lacking. The aim of this study was to estimate the prevalence and characterize the neuropsychological impairment in lacunar stroke patients. Methods All English-speaking participants in the SPS3 trial (NCT: 00059306) underwent neuropsychological testing at baseline. Raw scores were converted to z-scores using published norms. Those with impairment (z≤-1.5) in memory and/or non-memory domains were classified as having Mild Cognitive Impairment (MCI). Results Among the 1636 participants, average z scores on all tests were below zero with the largest deficits seen on tests of episodic memory (range of means -0.65 to -0.92), verbal fluency (mean -0.89), and motor dexterity (mean -2.5). Forty-seven percent were classified as having MCI: 36% amnestic, 37% amnestic multidomain, 28% non-amnestic. Of those with Rankin score 0-1 and Barthel score=100, 41% had MCI. Younger age [odds ratio (OR) per 10-yr increase=0.87], male sex (OR 1.3), less education (OR 0.13-0.66 compared to 0-4 yrs education), post-stroke disability (OR 1.4), and impaired activities of daily living (OR 1.8) were independently associated with MCI. Conclusions In this large, well characterized cohort of lacunar stroke patients, MCI was present in nearly half, including many with minimal or no physical disabilities. Cognitive dysfunction in lacunar stroke patients may commonly be overlooked in clinical practice but may be as important as motor and sensory sequelae.

Objectives-There is an enrichment of immune response genes that are subject to copy number variations (CNVs). However, there is limited understanding of their impact on susceptibility to human diseases. CC chemokine ligand 3 like-1 (CCL3L1) is a potent ligand for the HIV coreceptor, CC chemokine receptor 5 (CCR5), and we have demonstrated previously an association between CCL3L1-gene containing segmental duplications and polymorphisms in CCR5 and HIV/AIDS susceptibility. Here, we determined the association between these genetic variations and risk of developing systemic lupus erythaematosus (SLE), differential recruitment of CD3+ and CD68+ leukocytes to the kidney, clinical severity of SLE reflected by autoantibody titres and the risk of renal complications in SLE.Methods-We genotyped 1084 subjects (469 cases of SLE and 615 matched controls with no autoimmune disease) from three geographically distinct cohorts for variations in CCL3L1 and CCR5.Results-Deviation from the average copy number of CCL3L1 found in European populations increased the risk of SLE and modified the SLE-influencing effects of CCR5 haplotypes. The CCR5 human haplogroup (HH)E and CCR5-32-bearing HHG*2 haplotypes were associated with an increased risk of developing SLE. An individual's CCL3L1-CCR5 genotype strongly predicted the overall risk of SLE, high autoantibody titres, and lupus nephritis as well as the differential Conclusion-CCR5haplotypes HHE and HHG*2 strongly influence the risk of SLE. The copy number of CCL3L1 influences risk of SLE and modifies the SLE-influencing effects associated with CCR5 genotypes. These findings implicate a key role of the CCL3L1-CCR5 axis in the pathogenesis of SLE.

Depression, a modifiable risk factor, is associated with significantly poorer function in several cognitive domains in patients newly diagnosed with SLE. Treatment of depression when the CDS score is greater than 6 may improve cognitive functioning and should be further studied.