Neurodegenerative diseases, including Alzheimer’s and Parkinson’s, impose a growing global burden, with limited therapies targeting the underlying pathology. Emerging evidence implicates impaired glymphatic-lymphatic clearance of neurotoxic proteins (e.g., amyloid-β, tau, α-synuclein) as a key driver of disease progression.

This review evaluates lymphatic supermicrosurgery - a novel intervention enhancing meningeal and cervical lymphatic drainage - as a therapeutic strategy. Mechanistic studies demonstrate that restoration of lymphatic outflow reduces protein accumulation, attenuates neuroinflammation, and improves cognitive/motor function in preclinical models. 

Early clinical evidence demonstrates that cervical lymphatic-venous anastomosis (LVA) improves cognitive function and reduces pathological burden with improvements in neuropsychiatric symptoms. However, translational challenges remain substantial. Murine models poorly replicate human neurolymphatic ageing, particularly regarding glymphatic channel dimensions. Early clinical trials lack sham controls and standardised protocols, with procedural heterogeneity complicating interpretation. Additional limitations include small sample sizes, short follow-up periods, and unvalidated biomarker correlations. 

Future research requires multicentre RCTs with comprehensive neuropsychological batteries, advanced imaging, and tracking of long-term outcomes. While promising, widespread adoption necessitates the resolution of technical uncertainties and ethical considerations for cognitively impaired populations.