Serum clusterin, neurofilament light chain, and LDL-C cholesterol for risk stratification of cognitive impairment in parkinson’s disease

Abstract

Serum biomarkers, due to their advantages of easy accessibility and repeatability, show significant potential for early identification and stratification of cognitive impairment in Parkinson's disease (PD). This study aimed to systematically evaluate the expression differences of serum clusterin (CLU), neurofilament light chain (NFL), and LDL-C levels in PD patients with different cognitive statuses through a retrospective analysis. 90 patients with primary clinically established PD, diagnosed between January 2025 and February 2026, were retrospectively enrolled and stratified by cognitive status into PD with normal cognition (PD-NC), mild cognitive impairment (PD-MCI), and dementia (PDD). 90 healthy individuals from the same period served as controls. Fasting venous blood was collected from all subjects to analyze serum levels of CLU, NFL, and LDL-C. Clinical data, including demographics, disease duration, Hoehn-Yahr stage, UPDRS-III, and MoCA scores, were also recorded. Correlation analysis was performed using Spearman's test. A binary logistic regression model was developed for risk prediction, and ROC curves were plotted to evaluate the diagnostic performance of individual biomarkers and the combined model. Serum CLU and NFL levels were significantly higher in the PD group than in healthy controls ( P < 0.001), increasing progressively across PD-NC, PD-MCI, and PDD. Conversely, LDL-C levels were significantly lower ( P < 0.001), showing an opposite decreasing trend. CLU and NFL correlated negatively with MoCA score, and positively with UPDRS-III scores, while LDL-C showed the reverse pattern (all P < 0.001). A predictive model incorporating Hoehn-Yahr stage, UPDRS-III score, and serum CLU, NFL, and LDL-C levels excellently discriminated PD cognitive impairment (AUC = 0.921). Serum CLU, NFL, and LDL-C are potential effective biomarkers for cognitive impairment in PD. Their combined detection can effectively differentiate PD cognitive statuses and shows good risk stratification capability. This study provides an important serological tool for the early screening, disease monitoring, and intervention assessment of cognitive impairment in PD, with certain clinical translational value.