Deep cervical lymphatic-venous anastomosis in dementia: a clinical and mechanistic evaluation

Background: Alzheimer's disease (AD) and other dementias are marked by progressive cognitive decline, with few effective treatments available in advanced stages. Impaired clearance of neurotoxic proteins such as amyloid-beta (Aβ) and tau is a central pathological feature. Deep cervical lymphatic-venous anastomosis (dcLVA) is a novel microsurgical approach designed to enhance cerebrospinal fluid (CSF) clearance via extracranial lymphatic pathways, potentially enabling removal of neurotoxic proteins. Objective: To evaluate the clinical effects and potential mechanisms of dcLVA in patients with advanced dementia, focusing on cognitive, functional, and immunopathological outcomes. Methods: Twenty-eight patients with advanced dementia underwent dcLVA. Cognitive performance was assessed using the Mini-Mental State Examination (MMSE), alongside evaluations of bowel and bladder control, emotional stability, behavioral responsiveness, and self-care abilities. Biological parameters-including CSF protein, tumor markers, lymphocyte counts, and peripheral blood concentrations of Aβ1-42 and phosphorylated tau-181 (P-tau181)-were measured pre- and postoperatively. Immunohistochemical analysis of resected cervical lymph nodes was performed to detect CNS-derived tau protein. Results: Within one week after dcLVA, 64.3% of patients demonstrated MMSE improvement, with further functional gains observed in continence, emotional regulation, motor coordination, and feeding independence. Patients with circulatory comorbidities were more likely to show cognitive recovery. Tau protein was detected in all examined cervical lymph nodes, providing direct histopathological evidence of CNS-derived pathological protein transport via the lymphatic system. In a subset of cognitively improved patients, peripheral lymphocyte counts normalized. In contrast, tumor markers and CSF total protein showed no significant correlation with outcomes. Conclusions: dcLVA may promote cognitive and functional recovery in patients with dementia by enhancing CNS waste clearance and modulating systemic immune responses. These exploratory findings describe postoperative changes observed in this cohort; however, the single-arm design precludes causal interpretation.