Glymphatic System Alterations in Lung Cancer Patients with Chemotherapy-Related Cognitive Impairment

Chemotherapy-related cognitive impairment (CRCI) is a common adverse effect among lung cancer patients undergoing chemotherapy. Glymphatic system dysfunction has been implicated in the pathogenesis of cognitive deficits. This study aimed to investigate the impact of chemotherapy on the glymphatic system in patients with non-small cell lung cancer (NSCLC) and its association with cognitive outcomes.

A total of 102 NSCLC patients, including 53 patients without chemotherapy (CT(-)), 49 patients with chemotherapy (CT(+)), and 56 healthy controls (HCs), were enrolled. Glymphatic function was assessed using the diffusion tensor image analysis along the perivascular space (DTIALPS) index and choroid plexus (CP) volume. Group differences and correlations with neurocognitive performance were examined.

Significant differences in the DTI-ALPS index and CP volume were observed among the three groups. Post-hoc analyses revealed that the CT(+) group had significantly lower DTI-ALPS indices and larger CP volumes than both the CT(-) and HCs (p < 0.05). The DTI-ALPS index was positively correlated with MoCA scores (r = 0.448, p = 0.001), while CP volume was negatively correlated with MoCA scores (r = -0.435, p = 0.002). Moreover, the DTI-ALPS index partially mediated the relationship between CP volume and MoCA scores (mediation effect = 32.79%).

The DTI-ALPS index and choroid plexus (CP) volume serve as comprehensive metrics for assessing global glymphatic function. Previous studies have found that chemotherapy has differential effects on the structure and function of various brain regions, including the hippocampus and prefrontal cortex.

This study provides novel insights into the neural mechanisms underlying CRCI in NSCLC patients, highlighting the role of reduced DTI-ALPS index and enlarged CP volume in CRCI pathogenesis. These findings suggest that glymphatic metrics may serve as potential biomarkers for CRCI.