Cognitive dysfunction in systemic lupus erythematosus: A pilot study on the role of serum neuron-specific enolase levels

Abstract

Introduction

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that often manifests during productive years and frequently involves the central nervous system (CNS), including cognitive dysfunction, which occurs at twice the prevalence of the general population. While the Montreal Cognitive Assessment (MoCA) is effective for detecting mild cognitive impairment, no reliable biomarkers that indicate SLE patients at risk of cognitive dysfunction exist. Neuron-specific enolase (NSE), a specific marker of neuronal cell damage, has been shown in several studies to be highly expressed in cognitive dysfunction. This study serves as a preliminary investigation to examine the relationship between serum NSE levels and cognitive function in SLE patients.

Methods

A cross-sectional study was conducted from January to August 2024 at Hasan Sadikin General Hospital, including SLE patients aged 18–55 years meeting the EULAR/ACR 2019 criteria. Exclusion criteria included pregnancy, neurological disorders (e.g., CNS infections, neurodegenerative diseases, stroke, epilepsy, head trauma), psychiatric conditions, substance abuse, systemic metabolic disorders, malignancy, other autoimmune diseases, or HIV. Cognitive function was assessed using MoCA-Indonesian version (MoCA-Ina) and serum NSE levels were measured. Associations between serum NSE and MoCA-Ina scores were analyzed using Spearman’s correlation (p < .05).

Results

Eighty-one participants (median age 32 years; 93.8% female) were included. Cognitive dysfunction (MoCA-Ina <26) was identified in 38.3%. Median serum NSE levels were higher in participants with cognitive dysfunction compared to those with normal cognition (14.0 ng/mL vs 12.7 ng/mL). Serum NSE levels showed a negative correlation with MoCA-Ina total scores (r = −0.225, p = .022) and executive function (r = −0.204, p = .034). Cognitive dysfunction was also associated with longer disease duration and a history of seizures.

Conclusion

This study demonstrates a significant association between neuronal injury, as indicated by elevated serum neuron-specific enolase (NSE) levels, and cognitive impairment in SLE patients, with a particular impact on executive function. Longitudinal studies incorporating neuronal biomarkers are essential to provide deeper insights into the progression of cognitive dysfunction in SLE patients.