Serum cystatin C and cognitive function in midlife: results from the Hanzhong Adolescent Hypertension Study

Cystatin C (CysC), a low-molecular-weight protein, is widely used as a biomarker of renal function. The relationship between CysC and cognitive impairment remains controversial. This study aimed to investigate the association between CysC and cognitive impairment in the Hanzhong Adolescent Hypertension Study.

A total of 2,347 participants completed the Mini-Mental State Examination (MMSE) in 2023, after excluding the participants missing data, 1929 participants were included. Multivariable logistic regression was used to assess the cross-sectional association between serum CysC levels and cognitive impairment. Subgroup and interaction analyses were performed to examine effect modification by albuminuria status. The nonlinear relationship was explored using restricted cubic splines (RCS).

Cognitive impairment was identified in 149 participants (7.72%). Each 1-SD increase in CysC levels was significantly associated with 49% higher odds of cognitive impairment after full adjustment [odds ratio (OR) = 1.49, 95% confidence interval (CI): 1.24-1.79, p < 0.001]. Compared with participants in the lowest CysC quartile, those in the highest quartile had significantly higher odds of cognitive impairment (OR = 1.79, 95% CI = 1.09-2.98, p = 0.022). The association was stronger in participants without albuminuria (OR per SD = 1.48, 95% CI: 1.22-1.80, p < 0.001) but absent in those with albuminuria (OR per SD = 1.00, 95% CI: 0.73-1.25, p = 0.981), with a significant interaction when CysC was modeled continuously (p for interaction = 0.028). A linear and positive association was observed between cystatin C levels and the prevalence of cognitive impairment (p for linearity < 0.001). This association remained significant in the non-albuminuria subgroup.

Elevated CysC is associated with cognitive impairment assessed by MMSE in this midlife natural population cohort. This association is stronger in participants without albuminuria.