COGNITIVE impairment in patients with systemic lupus erythematosus (SLE) may be linked to elevated serum neuron-specific enolase (NSE) levels, according to new pilot research exploring the role of this neuronal injury biomarker.
SLE is a chronic autoimmune disease that often affects the central nervous system and has a cognitive dysfunction prevalence twice that of the general population. While tools such as the Montreal Cognitive Assessment (MoCA) can detect mild impairment, reliable biomarkers for identifying at-risk patients have been lacking. NSE, a marker of neuronal cell damage, has been implicated in cognitive decline in other contexts, prompting this study to examine its potential relevance in SLE.
In this cross-sectional study conducted between January and August 2024 at Hasan Sadikin General Hospital, 81 SLE patients aged 18–55 years meeting EULAR/ACR 2019 criteria were assessed. Participants with confounding neurological, psychiatric, metabolic, or systemic conditions were excluded. Cognitive performance was evaluated using the MoCA-Indonesian version (MoCA-Ina), and serum NSE levels were measured.
Cognitive dysfunction, defined as a MoCA-Ina score below 26, was identified in 38.3% of participants. Those with impairment had higher median NSE levels compared to cognitively normal patients (14.0 ng/mL vs 12.7 ng/mL). Statistical analysis revealed a negative correlation between serum NSE levels and total MoCA-Ina scores (r = –0.225, p = .022) as well as executive function performance (r = –0.204, p = .034). Cognitive dysfunction was also more common in patients with longer disease duration and a history of seizures.
The findings suggest that elevated NSE may be a marker of neuronal injury contributing to cognitive decline in SLE, particularly in domains related to executive function. The authors note that larger, longitudinal studies incorporating neuronal biomarkers are needed to better understand the progression and potential reversibility of cognitive dysfunction in lupus.
Reference
Aulia Putri Ay et al. Cognitive dysfunction in systemic lupus erythematosus: A pilot study on the role of serum neuron-specific enolase levels. Lupus. 2025. doi:10.1177/09612033251366396.
