Association between diffusion tensor imaging analysis along the perivascular space (DTI-ALPS)-based glial-lymphatic dysfunction and cognitive impairment in non-small cell lung cancer.

[OBJECTIVE] To investigate the correlation of glial-lymphatic (glymphatic) system function with cognitive deficits in non-small cell lung cancer (NSCLC).

[METHODS] Data (demographic, clinical, and magnetic resonance imaging [MRI] information) from 83 NSCLC cases and 96 healthy controls were retrospectively analyzed. We evaluated glymphatic activity by using the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index and cognitive function with the Montreal Cognitive Assessment (MoCA). Medial Temporal Atrophy (MTA) and Fazekas scores were also rated. Statistical analyses included inter-group comparisons, partial correlation assessments, mediation modeling, and regression to identify predictors of cognitive impairment.

[RESULTS] NSCLC patients had higher MTA and Fazekas scores but lower MoCA and ALPS index scores than controls (all P < 0.05). The ALPS index was symmetrically reduced in both hemispheres, correlating positively with MoCA (r = 0.276, P = 0.012). In the mediation model, the ALPS index exhibited a partial mediating role (4.6%) in the NSCLC-MoCA association. Older age was an independent predictor of cognitive impairment (odds ratio [OR]: 1.229; 95% confidence interval [CI]: 1.111-1.360).

[CONCLUSION] In NSCLC patients, glymphatic dysfunction was associated with cognitive impairment, and the DTI-ALPS index may facilitate early detection of these deficits. Advanced age remains a major contributing risk factor.