Deep cervical lymphovenous reconstruction in Alzheimer's disease: three target-defined interfaces with distinct mechanistic implications.

Abstract

Age-related impairment of brain solute clearance has been implicated in Alzheimer's disease (AD), yet procedures described as deep cervical lymphovenous reconstruction do not necessarily target the same lymphatic structure. This review examines glymphatic exchange, meningeal lymphatic drainage, cervical outflow, human lymphatic imaging, lymphatic surgery, early clinical studies, registered trials, and reported harms. Three interfaces can be distinguished: lymphatic flap-vein, lymph node-vein, and collecting lymphatic vessel-vein anastomosis. They differ in the reconstructed structure, pressure-flow conditions, sensitivity to nodal resistance and venous back pressure, likely failure modes, and the extent to which patency can be tested directly. Human evidence remains largely uncontrolled, short term, and incompletely reported. Recent mouse, cadaveric, proteomic, and retrospective clinical reports broaden the evidence base but do not establish a human cervical bottleneck or clinical efficacy. Biomarker changes are hypothesis-generating rather than evidence of enhanced cerebral clearance, and a delayed report of neurological, infectious, and immune events indicates the need for surveillance beyond the perioperative period. Credible evaluation requires biological confirmation of AD, a measurable clearance-axis phenotype, a suitable cervical target, explicit operative reporting, directional target-level flow with durable patency, concordant imaging and biomarker findings, perioperative and long-term neurological and systemic safety assessment, a controlled longitudinal design, and blinded patient-level outcomes. Collecting lymphatic vessel-vein anastomosis is the most anatomically defined construct for standardized mechanistic testing; lymph node-vein anastomosis depends on functional nodal screening and sustained flow; and lymphatic flap-vein anastomosis remains an exploratory mixed interface. This is a research-design ordering based on target definition and testability, not a therapeutic ranking, evidence of efficacy, or evidence of clinical superiority.