Exploring Lymphovenous Anastomosis for Alzheimer Disease: Addressing Brain Lymphatic Dysfunction, Feasibility, and Outcome Metrics.

Abstract

Alzheimer disease is a multifactorial neurodegenerative disorder characterized by amyloid-beta plaques, tau tangles, and neuroinflammation, with emerging evidence highlighting a potential role for brain lymphatic dysfunction. Lymphovenous anastomosis (LVA), a microsurgical technique traditionally used in lymphedema management, offers a novel solution to enhance brain metabolite clearance by bypassing impaired lymphatic pathways and enhancing glymphatic outflow. By connecting lymphatic vessels to veins, LVA compensates for aging-related declines in lymphatic/glymphatic flow, with preliminary studies supporting this theory. This review evaluates the feasibility of LVA, emphasizing key anatomical targets such as cervical lymphatic vessels, while proposing robust patient selection criteria. It also aims to address the controversies in outcome measures including advanced imaging, biomarker analysis, and cognitive assessments. Although early findings are promising, further research is essential to optimize surgical protocols, clarify biological mechanisms, and ensure safety. LVA represents a novel therapeutic strategy that may complement existing treatments, offering new hope for addressing the inevitable outcome of Alzheimer disease.