Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by pathological protein accumulation in the brain-Aβ/tau in AD and α-synuclein in PD. Recent studies have indicated that age-related lymphatic vessel atrophy compromises the metabolic clearance capacity of meningeal lymphatic vessels, potentially disrupting the equilibrium between production and clearance of Aβ/α-synuclein, ultimately leading to pathological accumulation of these proteins within the brain. Deep cervical lymphovenous anastomosis (LVA), a surgical technique proven effective in restoring lymphatic drainage in lymphedema, may enhance clearance of neurotoxic proteins by improving cervical lymphatic outflow. This project aims to evaluate the efficacy of modified deep cervical LVA in treating AD and PD, establishing a novel therapeutic strategy to modify disease progression and improve quality of life in neurodegenerative disorders, additionally offering the pathogenic mechanisms underlying neurodegenerative disorders.
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)
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;
Single group
Modified deep cervical Lymphatic-Venous Anastomosis
Procedure/SurgeryDeep cervical lymph-vein anastomosis surgery, connecting deep cervical lymph input vein vessels to enhance glymphatic-mediated protein clearance
Alzheimer's disease: Change in Clinical Dementia Rating Scale sum of the boxes (CDR-SB)
The Clinical Dementia Rating Scale sum of the boxes (CDR-SB) will be used to evaluate the general cognitive function. CDR-SB ranges from 0 to 18, and higher value represents a worse outcome.
Alzheimer's disease: Change in Mini-mental State Examination (MMSE)
The Mini-mental State Examination (MMSE) will be used to evaluate the general cognitive function. MMSE ranges from 0 to 30, and higher value represents a better outcome.
Alzheimer's disease: Change in Montreal Cognitive Assessment (MoCA)
The Montreal Cognitive Assessment (MoCA) will be used to evaluate the general cognitive function. MoCA ranges from 0 to 30, and higher value represents a better outcome.
Alzheimer's disease: Change in Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (Severe Version) (ADCS-ADL-SEV)
The ADCS-ADL-SEV consists of 19 items. Ratings reflect caregiver observations about the patient's actual functioning over the previous month and provide an assessment of change in the functional state of the participant over time. The total score ranges from 0 to 54, with lower values over time reflecting functional deterioration.
Alzheimer's disease: Change in amyloid deposit in brain
Change from baseline as measured by amyloid positron emission tomography (PET) scan using centiloids. The centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scan. A negative change indicates an improvement from baseline.
Alzheimer's disease: Change in brain Tau deposition in a subset of participants
Change from baseline as measured by Tau PET scan
Alzheimer's disease: Change in fluid biomarker
Change from baseline in cerebrospinal fluid (CSF)/plasma p-tau217, p-tau181, Aβ42, GFAP and NfL levels
Alzheimer's disease: Change in Neuropsychiatric Inventory (NPI-Q) Total Severity Score
The NPI-Q is a brief, caregiver-reported assessment of neuropsychiatric symptoms associated with dementia. The NPI-Q yields total scores for Severity and Distress, reflecting the sum of ratings across all domains, with higher scores indicating a greater degree of symptom severity and caregiver distress, respectively.
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Zhejiang Provincial People's Hospital
Lead sponsor
Zybio Inc.
Collaborator
