An Exploratory Study to Confirm Efficacy of Modified Deep Cervical Lymphovenous Anastomosis (LVA) in Alzheimer's Disease/ Parkinson's Disease

Alzheimer's disease (AD) and Parkinson's disease (PD) are progressive neurodegenerative disorders characterized by pathological protein aggregation-Aβ plaques and tau tangles in AD, and α-synuclein Lewy bodies in PD. Emerging evidence implicates that the glymphatic-meningeal lymphatic system and deep cervical lymph nodes constitute the central pathway for metabolite clearance of cerebral macromolecules. Aging-associated lymphatic vessel atrophy disrupts the equilibrium between protein production and clearance, exacerbating neurotoxicity. Deep cervical lymphovenous anastomosis (LVA), a surgical technique validated in lymphedema management, aims to restore cervical lymphatic drainage and enhance glymphatic-mediated protein clearance. This study investigates the therapeutic potential of modified deep cervical LVA in AD and PD. A prospective cohort will undergo modified deep cervical LVA with longitudinal assessments, including cerebrospinal fluid (CSF) and plasma biomarkers (Aβ42, p-tau181, p-tau217, GFAP, NfL, α-synuclein), neuroimaging (MRI and PET-CT), and clinical endpoints (CDR, MMSE, MoCA, BADL and IADL for AD, UPDRS and PDQ-39 for PD). Mechanistically, we hypothesize that modified deep cervical LVA will reduce intracranial pressure gradients, augment meningeal lymph flow, and accelerate interstitial waste drainage, thereby mitigating neuroinflammation and neuronal damage. This trial aims to verify the efficacy of modified deep cervical LVA to modify disease progression in AD and PD, providing a surgically scalable approach to delay progression of neurodegenerative disorders and improve patient quality of life.

Inclusion criteria

Alzheimer's disease:

• Male or female, the age ranged from 50 to 75 years old
• Informed consent signed and dated by patient or legal representative
• Patients diagnosed principally with mild cognitive impairment or dementia caused by Alzheimer's disease
• Positive result of Amyloid PET imaging (Centiloids ≥37)
• HAMD score ≤17
• Hachinski score ≤4 Patients who meet ASA (American Society of Anesthesiologists) grade I-III criteria

Parkinson's disease:

• Male or female, the age ranged from 50 to 80 years old
• Informed consent signed and dated by patient or legal representative
• Patients diagnosed with Parkinson's disease or probable Parkinson's disease according to the Clinical Diagnostic Criteria for Parkinson's Disease in China (2016) or MDS
• Stage I-IV patients according to Hoehn and Yahr Scale
• Patients documented history of Parkinson's disease for more than 2-5 years to ensure clinical stability of symptoms and exclude the possibility of early misdiagnosis of other conditions

Exclusion criteria

• Contraindications for MRI, ICG angiography, or PET scanning
• Contraindications for lumbar puncture
• Functional impairment of vital organs (cardiac, pulmonary, renal, hepatic), including reduced left ventricular ejection fraction, prolonged QT interval, severe pulmonary diseases, and severe hepatic/renal insufficiency
• MRI results suggesting intracranial active/acute pathologies, including infections, space-occupying lesions, major hemorrhages, or ≥4 lobar microhemorrhages;
• Conditions predisposing to increased intracranial hemorrhage risk, such as hematological disorders, hemorrhagic/coagulation disorders;
• Poorly controlled thyroid dysfunction;
• Cerebrovascular or systemic vasculopathy;
• Severe cardiac disease or hemodynamic instability;
• Uncontrolled severe hypertension;
• Substance use disorders (including illicit drugs, anesthetics, and alcohol dependence);
• Active severe infections, including HIV positivity and acute critical infections;
• Severe psychiatric disorders or significant suicide risk;
• Chronic hypnotic use (more than twice weekly for over one month);
• History of untreated/uncured malignancies;
• Participation in other interventional clinical trials within preceding 3 months;
• Poor compliance with inability/unwillingness to complete scheduled postoperative follow-ups;
• Other investigator-determined contraindications for trial participation.