The impaired white-matter structural network mediates the relationship between the glymphatic system and emotional abnormalities in patients with chronic kidney disease.

Background: Patients with chronic kidney disease (CKD) tend to have white-matter network and glymphatic system dysfunction, and may experience cognitive decline and psychiatric abnormalities. This study explored the relationships between graph theory-based white-matter networks and diffusion tensor image analysis along the perivascular space (DTI-ALPS) and the choroid plexus volume (CPV).

Methods: Sixty-one CKD patients, including 22 non-dialysis dependent (NDD) and 39 dialysis-dependent (DD) patients, and 43 age-, gender-, and education-matched healthy control (HC) participants were recruited for the study. All participants underwent blood biochemical tests, neuropsychological assessments, and magnetic resonance imaging scans. Preprocessed images were used to construct fractional anisotropy networks, and calculate the DTI-ALPS index and CPV. Intergroup comparisons were performed for all measurements, and correlations were analyzed.

Results: Compared to the HCs, the DD-CKD patients had elevated small-worldness (σ) and normalized clustering coefficient (P<0.01) values, while no significant statistical differences were observed between NDD-CKD patients and the HCs. The clustering coefficient (P<0.05), and global and local efficiency (P<0.01) values were decreased, while the characteristic path length (P<0.01) was increased in the CKD patients, especially those who were DD. The CKD patients also had decreased DTI-ALPS index (P=0.001) and increased CPV (P<0.001) values. These indicators were correlated with verbal memory, anxiety, and depression levels (all P<0.05). The mediation analysis revealed that σ partially mediated the effect of the DTI-ALPS index on depression levels (mediation effect: -5.0404), σ fully mediated the effect of the CPV on depression levels (mediation effect: 0.0013), and σ fully mediated the effect of the DTI-ALPS index on anxiety levels (mediation effect: -5.9291).

Conclusions: CKD patients exhibit impaired glymphatic system function and abnormal white-matter network topology, both of which are correlated with cognition, verbal memory, and emotional states. The structural integrity and organizational efficiency of white-matter networks may be a critical factor linking glymphatic dysfunction to emotional health in CKD patients.