Prospective Single-Arm Safety Study of Cervical LVA in AD Patients

Official Title Prospective Single-Arm Safety Study of Cervical Lymphaticovenular Anastomosis (LVA) in Patients with Alzheimer's Disease Scientific Rationale Neurodegenerative diseases like Alzheimer's (AD) are characterized by the misfolding and accumulation of proteins such as Amyloid-beta and Tau. The glymphatic and meningeal lymphatic systems serve as the primary pathways for clearing these metabolic wastes from the central nervous system into the deep cervical lymph nodes. This study investigates whether enhancing this drainage via supermicrosurgical lymphaticovenular anastomosis (LVA) can reduce intracranial protein burden and systemic oxidative stress. Study Design and Intervention This is a prospective, single-arm safety study. Participants undergo bilateral cervical LVA. Using Indocyanine Green (ICG) fluorescence lymphography for navigation, lymphatic vessels in the neck are identified and anastomosed to adjacent small veins to facilitate lymph drainage into the venous circulation. Safety Monitoring and Data Integrity Primary Safety Endpoint: The study defines safety as a Serious Adverse Event (SAE) rate of ≤10% within the first month post-operation. Events are graded using CTCAE v5.0. Independent Oversight: To ensure objectivity, cognitive and behavioral assessments (including MMSE, CDR, and CASI) are conducted by clinical psychologists who are not members of the core research team. External Auditing: An independent Clinical Research Organization (CRO) has been contracted to perform four periodic audits to verify data accuracy and GCP compliance. Exploratory Objectives The study will track longitudinal changes in: Fluid Biomarkers: Plasma levels of Amyloid-beta 40/42, p-Tau 217, GFAP, and Nf-L at baseline, 1, 6, and 12 months. Neuroimaging: Amyloid-PET and FDG-PET scans at baseline and 12 months to evaluate protein deposition and metabolic activity. Clinical Outcomes: Changes in cognitive scores (CDR, MMSE, CASI, NPI) from baseline to 6 months post-surgery.