Prevalence and clinical associations of cerebral atrophy in systemic lupus erythematosus.

To determine the prevalence of cerebral atrophy in a multi-ethnic systemic lupus erythematosus (SLE) cohort and to identify its associated clinical factors. In this cross-sectional study (2024-2025), adults fulfilling the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for SLE at University Malaya Medical Centre were recruited. Demographic, clinical, serological, vascular and treatment data were collected. Disease activity and cumulative damage were assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Non-contrast CT brain scans were performed with cerebral atrophy graded using the validated Global Cortical Atrophy (GCA) score. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA). Fisher's exact test and χ2 test were used to test the association between two categorical variables where appropriate, while group differences were tested using the Mann-Whitney U test. Univariable and multivariable logistic regression analyses were considered to identify variables that were significantly associated with cerebral atrophy. Seventy patients (92.9% female; median age 40 (IQR 31.75-50.25) years; median disease duration 12 (IQR 4-19) years were included. Cerebral atrophy was present in 52.9%, predominantly mild (75.7%). From univariate comparisons, patients with cerebral atrophy were significantly older in age, had longer disease duration, lower education, higher SDI and poorer MoCA scores. Multivariable analysis showed that older age (OR 1.10 per year, 95% CI 1.04 to 1.18) and neuropsychiatric SLE (NPSLE) (OR 4.58, 95% CI 1.05 to 24.07) contributed to increased odds of cerebral atrophy, while higher educational attainment was linked with reduced odds of cerebral atrophy (OR 0.22, 95% CI 0.06 to 1.03). Cerebral atrophy is common in SLE and independently associated with age, education, NPSLE and cognitive impairment, reflecting neuroinflammatory and neurodegenerative mechanisms. These findings underscore the importance of cognitive screening and targeted monitoring of high-risk patients.