DTI-ALPS index correlates with poor neuromodulation outcomes of bilateral STN-DBS in Parkinson's disease patients: A prospective cohort study.

This prospective study evaluated whether preoperative glymphatic magnetic resonance imaging (MRI) markers predict subthalamic nucleus deep brain stimulation (STN-DBS) outcomes in Parkinson's disease (PD) and examined the mediating role of levodopa responsiveness. 111 patients with idiopathic PD scheduled for bilateral STN-DBS underwent multimodal preoperative MRI. Glymphatic indices-choroid plexus volume (CPV), diffusion tensor image analysis along the perivascular space (DTI-ALPS), perivascular space burden, choroid plexus free-water fraction, and global blood-oxygen-level-dependent cerebrospinal fluid coupling-were quantified. Patients were stratified by median postoperative motor improvement (52.4%) into high- (n = 55) and low-improvement (n = 56) groups. The low-improvement group showed significantly larger total CPV (3353.7 vs 3199.4 mm³, p = 0.039) and lower bilateral DTI-ALPS (1.34 vs 1.42, p = 0.004). DTI-ALPS correlated positively with both STN-DBS outcome (r = 0.246, p = 0.009) and levodopa challenge test (LCT) efficacy (r = 0.196, p = 0.039). Mediation analysis revealed that the DTI-ALPS effect on STN-DBS outcome was partially mediated by LCT (indirect effect 0.096, 95% bootstrap CI 0.013-0.188), accounting for 50.8% of the total effect. Other glymphatic markers showed no significant associations with DBS outcome. These findings indicate that glymphatic dysfunction, indexed by reduced DTI-ALPS, associates with poorer STN-DBS response in PD, acting partly through diminished dopaminergic reserve. DTI-ALPS may serve as an adjunctive preoperative marker to improve patient selection beyond conventional LCT.