Reduced global BOLD-CSF coupling in chronic kidney disease-related cognitive impairment: a resting-state functional...

Cognitive impairment is a common complication of chronic kidney disease (CKD), but its underlying mechanisms are not fully understood. This study aims to investigate the glymphatic system function in CKD patients with and without cognitive impairment (CI) by analyzing the coupling between the global blood oxygen level-dependent (gBOLD) signal and the cerebrospinal fluid (CSF) signal using resting-state functional magnetic resonance imaging (rs-fMRI).

Twenty-nine patients with CKD were enrolled (19 with CI and 10 without), along with 22 healthy controls (HCs). All patients underwent high-resolution structural MRI and rs-fMRI scans. The gBOLD-CSF coupling was quantified by calculating the maximum negative correlation within a predefined time-lag range between the gBOLD signal and the fourth ventricular CSF signal. The gBOLD-CSF coupling was compared between the CKD and HC groups using analysis of covariance (ANCOVA), adjusting for age, sex, education, and mean framewise displacement (FD). The difference between patients with CKD with and without CI was assessed using ANCOVA, after adjusting for age, sex, education, hypertension, diabetes, and mean FD. Partial correlation analysis was performed to explore the associations between gBOLD-CSF coupling and clinical indicators, such as estimated glomerular filtration rate (eGFR), Montreal Cognitive Assessment (MoCA) scores, and other laboratory data.

After adjusting for covariates, gBOLD-CSF coupling was significantly lower in the CKD group than in the HC group (β = -0.178, p = 0.003). This finding remained robust in sensitivity analyses adjusting for hypertension and diabetes. Within the CKD group, patients with CI had significantly lower gBOLD-CSF coupling than those without CI (β = -0.135, p = 0.040). Correlation analyses revealed that gBOLD-CSF coupling tended to be positively associated with hemoglobin, MoCA score, and eGFR, and negatively associated with blood urea and creatinine; however, none of these correlations reached statistical significance after false discovery rate correction (all q > 0.05).

Patients with CKD exhibit impaired glymphatic system function, manifested as reduced gBOLD-CSF coupling, which is associated with the severity of CI. These findings support the hypothesis that impaired glymphatic clearance may contribute to cognitive decline in CKD via the kidney-brain axis. Larger longitudinal studies are needed to validate its clinical significance.