NPH Glymphatic System Interaction Experiment

SUMMARY

# NPH Glymphatic System Interaction Experiment ## Background and Rationale Normal Pressure Hydrocephalus (NPH) is a neurodegenerative condition characterized by ventricular enlargement, gait disturbances, cognitive decline, and urinary incontinence. Recent advances in understanding the glymphatic system—the brain's waste clearance network that facilitates cerebrospinal fluid (CSF) flow through perivascular spaces—suggest a potential mechanistic link between glymphatic dysfunction and NPH pathoph

METHODOLOGY NOTES

Phase 1 (Screening, Days -14 to 0): Recruit 120 NPH patients meeting Hakim-Adams criteria. Obtain informed consent, perform baseline neuropsychological assessment (MMSE, MoCA, Stroop test), lumbar puncture for CSF biomarkers (Aβ42, total tau, phospho-tau, NFL, YKL-40), and baseline DTI-ALPS MRI scanning. Phase 2 (Randomization, Day 0): Randomize patients 1:1 to control group (standard VP shunt only, n=60) or intervention group (VP shunt plus glymphatic enhancement therapy, n=60). Phase 3 (Intervention, Days 1-90): Control group receives standard VP shunt placement and management. Intervention group receives VP shunt plus targeted glymphatic enhancement including optimized sleep positioning (30-degree lateral), melatonin supplementation (3mg nightly), and intermittent pneumatic compression therapy during sleep. Phase 4 (Assessment, Days 30, 90, 180, 365): Repeat DTI-ALPS MRI, neuropsychological testing, gait analysis (10-meter walk test, TUG), and CSF sampling at each timepoint. Monitor