Deep cervical lymphovenous anastomosis (LVA) for Alzheimer’s disease microsurgical procedure in a prospective cohort study

Objectives: Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder, characterized by progressive cognitive decline. Current approved drugs merely relieve symptoms rather than halt or reverse disease progression. The role of the brain lymphatic system in clearing harmful substances in the brain has provided new insights for AD treatment. The goal of this study was to assess the efficacy and safety of deep cervical lymphovenous anastomosis (LVA) in treating AD patients. Materials and methods: A single-center, prospective, single-arm exploratory study was conducted on 26 AD patients who met the clinical and biomarker diagnostic criteria of the National Institute on Aging-Alzheimer’s Association (NIA-AA). Deep cervical LVA was performed with modified technique from lymphatic vessel-vein to lymphatic flap-vein anastomosis. Preoperative and follow-up neuropsychological tests were carried out using Mini-Mental Status Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Neuropsychiatric Inventory (NPI) scores. Cerebrospinal fluid (CSF) biomarkers (Aβ42, Aβ40, p-Tau, T-Tau) were collected and analyzed via single-molecule immunoassay in the early postoperative period. Results: One month after surgery, about 60% of caregivers reported varying degrees of overall symptom improvement in patients. MMSE scores of patients significantly increased after surgery compared with before surgery (3 [0, 6] vs. 5 [0, 7], P = 0.022). Although, 15% of patients had increased MoCA scores, 42% had decreased NPI scores, both changes did not reach statistical difference. Quantitative analysis revealed a trend toward reduced AD biomarker levels following LVA, but the differences did not reach statistical significant. Only two patients experienced postoperative difficulty raising their arms, with gradual recovery during follow-up. Conclusion: This study demonstrates that deep cervical LVA is safe and feasible procedure, showing a significant cognitive improvement in AD patients (mainly in MMSE), which needs long-term follow-up and large-scale clinical trials to verify.