Deep cervical lymphaticovenous anastomosis for Alzheimer's disease: A narrative review

Abstract

Alzheimer's disease (AD) is a common neurodegenerative disorder with limited treatment options. Recent discoveries of the glymphatic system and meningeal lymphatic vessels (MLVs) have highlighted their critical role in clearing metabolic waste-including amyloid beta and tau proteins-from the brain. Dysfunction of these systems contributes to AD pathogenesis by impairing the clearance of neurotoxic proteins. Deep cervical lymphaticovenous anastomosis (dcLVA) is an innovative microsurgical technique designed to enhance cerebral waste drainage by anastomosing deep cervical lymphatic channels to adjacent veins. This narrative review synthesizes current evidence on the mechanisms, applications, and emerging perspectives of dcLVA for AD. Early studies suggest potential short-term improvements in cognitive scores and neuroimaging biomarkers after surgery, with an acceptable safety profile. However, the evidence is limited to small prospective cohorts and case reports, underscoring the need for larger, randomized controlled trials to validate its efficacy and long-term benefits. dcLVA represents a promising surgical intervention for select patients, particularly those with moderate-to-severe AD who have failed conventional pharmacotherapy, but it requires careful patient selection and further investigation. HIGHLIGHTS: This review proposes deep cervical lymphaticovenous anastomosis (dcLVA) as a mechanism driven surgery that may enhance clearance of amyloid beta (Aβ) and tau through the brain, meningeal, and deep cervical drainage pathways. Early human evidence from a single arm cohort and case reports suggests short term cognitive and imaging signals with acceptable perioperative safety. dcLVA is not recommended as a first line option for early Alzheimer's disease (AD) and may be considered for moderate to severe AD or for patients who are refractory to pharmacotherapy and have objective evidence of drainage impairment. Standardized patient selection and longitudinal imaging and biomarker monitoring are recommended, including Aβ and tau positron emission tomography (PET), diffusion tensor imaging (DTI) analysis along the perivascular space, and cerebrospinal fluid (CSF) or plasma panels. Systemic safety remains an important uncertainty, and future trials should include longitudinal surveillance of hepatic, renal, and hematologic function. Multicenter randomized controlled trials (RCTs) are urgently needed with 12 month Clinical Dementia Rating Sum of Boxes (CDR SB) as a primary endpoint, transparent reporting, and evaluation of combination strategies with anti Aβ therapies.

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