Serum cystatin C levels are independently correlated with cognitive impairment in individuals with cerebral small vessel disease

Background and purpose Previous studies have shown that serum cystatin C (CysC) is associated with cerebral small vessel disease (CSVD) and that elevated CysC levels are linked to an increased risk of cognitive impairment in the elderly. However, whether CysC is specifically associated with cognitive impairment in patients with CSVD remains unclear. Method A total of 334 CSVD patients with available demographic, blood biomarker, and brain imaging data were included. Patients were divided into vascular cognitive impairment and normal cognition groups. Univariate analysis was used to compare baseline data, blood biomarkers, imaging features, and behavioral scores between the two groups. Binary logistic regression was used to evaluate the diagnostic value of cystatin C for CSVD-related cognitive impairment. Results Compared with the normal cognition group, the VCI group exhibited significantly elevated serum levels of CysC, homocysteine, urea nitrogen, creatinine, uric acid, fibrinogen, and D-dimer, along with a lower red blood cell count. The VCI group also showed a higher prevalence of severe periventricular white matter hyperintensity, severe deep white matter hyperintensity, severe total white matter hyperintensity, and brain atrophy. The combination of these eight blood biomarkers markedly improved the diagnostic performance for VCI (AUC = 0.672, 95% CI: 0.615–0.730, p 0.001). Multivariate analysis revealed that elevated CysC levels (OR = 2.677, p = 0.041), age (OR = 1.067, p 0.001), and severe total WMH (OR = 2.713, p 0.001) were associated with CSVD-related cognitive impairment. After adjusting for confounding variables, serum CysC levels remained independently correlated with cognitive impairment (OR = 3.257, 95% CI: 1.192–8.899, p = 0.021). Conclusion Serum CysC levels are independently associated with cognitive impairment in CSVD patients.