Bypass the Brain: Deep Cervical Lymphatic-Venous Anastomosis Restores the Default Mode Network in Late-stage Alzheimer's Disease

Abstract The limited efficacy of late-stage Alzheimer’s disease (AD) therapies necessitates exploration of novel therapeutic strategies. Deep cervical lymphatic-venous anastomosis (dcLVA), a microsurgical procedure intended to augment cerebral drainage, represents a promising strategy, yet its efficacy lacks neurobiological evidence. In this longitudinal, single-arm study, 17 patients with moderate-to-severe AD underwent 7-Tesla resting-state functional MRI and neurocognitive assessment at baseline and at 1.52 ± 1.38 months post-dcLVA. Graph-theoretical analyses did not reveal significant reconfiguration of whole-brain network topology. Nevertheless, we observed selectively increased connectivity within the default mode network (DMN), most prominently in temporal regions. Cognitive function measured by mini-mental state examination was improved after dcLVA (p = 0.031), and was correlated with increased connectivity in bilateral temporal regions. To our knowledge, this study provided the first neuroimaging evidence that controversial dcLVA modulates functional networks in human patients with AD, and highlight DMN connectivity as a quantifiable biomarker for clearance-focused interventions.