Childhood lupus
Executive function was measured by the Delis-Kaplan Executive Function System Colour Word Interference Test. The test is comprised of four conditions (colour naming, word reading, inhibition and inhibition/ switching). We included scores for inhibition (ability to inhibit an automatic verbal response) and inhibi- tion/switching (ability to switch between different task demands), measuring cognitive inhibition and mental flexi- bility, respectively. 28 Performance is measured as comple- tion time in seconds for each condition. Raw scores were converted to age-normed scaled scores (mean=10, SD=3), with lower scores indicating worse executive function. Attention was measured by the computerised Conners Continuous Performance Test third edition. 29 Partici- pants were presented with letters on a screen one at a time at varying intervals and instructed to press the space bar when each letter appeared, except for the letter X. Nine age-normed T-scores (mean=50, SD=10) assessed different aspects of attention, with T-scores >60 indicating poorer performance. We included T-scores for omissions (sustained attention), commissions (impulsivity) and hit reaction time (response speed). Working memory was measured by the Wechsler Intelligence Scale for Children fifth Edition/Wechsler Adult Intelligence Scale, fourth Edition (for participants aged 16 years and older) Digit Span Test. 30 31 The task required participants to repeat strings of digits across three conditions: forwards, back- wards and in sequential order. Raw scores were converted to age-normed scaled scores (mean=10, SD=3), with higher scores indicating better performance. While there is not a standardly accepted definition for CD in cSLE, we used definitions in keeping with previous studies in this population which enabled capture of the range of cognitive difficulties across domains. 3 We defined overall CD as (1) performance on any of the cognitive domain tests of ≥ 2SD poorer than the mean standardised score or (2) performance on at least two tests (from different cognitive domains) of at least one SD poorer than the mean standardised score. We defined severe CD as performance on any of the cognitive domain tests of ≥ 2 SD poorer than the mean standardised score. Definitions for overall CD and severe CD were therefore not mutually exclusive. We also defined domain-specific CD as performance at least one SD poorer than the mean standardised score. Statistical analysis Descriptive statistics were used to summarise partic- ipants’ demographic and disease characteristics. We compared serum brain injury marker and cytokine levels between the cSLE and control groups using the Wilcoxon rank-sum test and analysed group differences in propor- tion of participants with CD using a χ 2 test. P values of <0.05 were considered statistically significant. We conducted three exploratory analyses. First, we exam- ined differences in brain injury marker levels between those with and without overall CD using Wilcoxon rank-sum tests. Second, we examined relationships between brain
categorised ethnicity into five mutually exclusive groups: Asian, black or African, European, Latin America and other (includes Arab/Middle Eastern, Indigenous, Pacific Islander and multiethnic). Disease variables Disease characteristics including disease duration (ie, time from diagnosis date to study visit), disease activity (Systemic Lupus Erythematosus 25 Disease Activity Index 2000 (SLEDAI-2K)), damage (SLICC/ACR Damage Index (SDI)), 25 26 presence of major organ disease (nephritis and/or NPSLE diagnosed by the treating rheumatol- ogist), hypocomplementaemia (low C3/C4 according to clinical lab cut-offs), positive anti-phospholipid anti- body status (positive anti-cardiolipin, anti-beta 2 glyco- protein or lupus anticoagulant according to clinical lab cut-offs), presence of abnormal clinical conventional brain MRI (determined by neuroradiologist reading), immunosuppressive medication and glucocorticoid (GC) (prednisone-equivalent dose) use were obtained through electronic medical records. SLEDAI-2K at study visit was calculated as both a continuous variable and binary vari- able for active disease (defined as a SLEDAI-2K score >4). We reviewed disease activity scores between the diag- nosis date and the study visit. To account for varying time intervals between clinic assessments, we calculated the adjusted mean SLEDAI-2K (AMS). 27 This was determined by calculating the area under the SLEDAI-2K curve (ie, the length of time between two SLEDAI-2K measurements multiplied by the average of the two measurements) over time by adding the area of each of the blocks of meas- urement interval and then dividing by the length of time for the whole period. 27 For those with only one visit, the AMS was equal to the SLEDAI-2K value for that visit, per the published definition. 27 We defined the presence of disease damage as an SDI score of >0 determined at the last clinic visit. GC use was defined as oral and/or intra- venous prednisone equivalent dose in mg. Current and cumulative GC dose (expressed in g is a summation of all oral and/or intravenous GCs ever received) was calcu- lated. Serum brain injury markers and cytokines Participant blood samples were collected with routine clinical blood draws for patients and during a study visit for controls. To maintain sample integrity, blood samples were stored in a −80 °C freezer after collection and processing and were shipped in batches on dry ice. Serum brain injury marker levels were quantified using ultra-sensitive Simoa assays to detect serum levels of sNFL, GFAP and Tau (Human Neurology 4–Plex B, Quanterix, Billerca, Massachusetts, USA) and IFN- α , IFN- γ and IL-6 (Quanterix, Billerca, Massachusetts, USA), with values expressed in pg/mL. Cognitive function measures Cognitive function was measured for the domains of executive function, attention and working memory.
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Mwizerwa O, et al . Lupus Science & Medicine 2026; 13 :e001922. doi:10.1136/lupus-2025-001922
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