Deep Cervical Lymphovenous Anastomosis for Severe Alzheimer's Disease

N/ANot Yet RecruitingNCT07669272

Southwest Hospital, China59 enrolled

Overview

Alzheimer's disease (AD) is a severe neurodegenerative disease with heavy social burden. Current drugs cannot reverse disease progression. Brain glymphatic system and meningeal lymphatic dysfunction lead to impaired clearance of Aβ and Tau protein, which is an important pathogenesis of AD. Deep cervical lymphovenous anastomosis (DCLVA) can improve intracranial lymphatic drainage, promote the clearance of toxic proteins, and improve neurological function. This is a single-arm, prospective, self-controlled study to enroll 59 patients with severe AD (MMSE \< 10). All patients receive bilateral DCLVA plus routine medication. The primary endpoint is change of CDR-SB score at 12 months post-operation. Secondary endpoints include MMSE, ZBI scores and Aβ PET-CT Centiloid value. This study aims to verify the efficacy and safety of DCLVA for severe AD.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Alzheimer s Disease

Interventions

A one-time microsurgical procedure performed under general anesthesia. Indocyanine green (ICG) is injected for intraoperative lymphatic vessel tracing under a fluorescent surgical microscope. Lymphatic vessels or lymphatic flaps are anastomosed to cervical veins via end-to-side or end-to-end technique to improve intracranial lymphatic drainage. No additional surgical interventions are applied.

Routine TreatmentOTHER

Stable administration of standard drugs for Alzheimer's disease, including cholinesterase inhibitors and/or NMDA receptor antagonists, following clinical guidelines. Participants continue their original medication regimen throughout the whole study period without dose adjustment or drug switching.

Eligibility

Sex: ALLMin age: 50 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Meet the 2011 NIA-AA clinical diagnostic criteria for probable Alzheimer's disease dementia and the 2018 NIA-AA research framework biomarker criteria for AD. * Aged 50 to 80 years (inclusive) at the time of signing informed consent. * Severe cognitive dysfunction: Mini-Mental State Examination (MMSE) score \< 10 points. * Progressive cognitive deterioration for more than 6 months reported by patient or caregiver. * No clinical improvement after more than 6 months of standardized drug treatment. * Have a designated study companion who signs informed consent, contacts the patient at least 10 hours per week and accompanies study visits. * Able to complete scale assessments and examinations independently or with companion assistance. * Voluntarily comply with study procedures, examinations and surgical treatment. * Patient or legal representative can sign written informed consent and abide by trial requirements. * Patients and families are informed of study purpose, expected efficacy and potential risks, and voluntarily provide biological samples and participate in the study. Exclusion Criteria: * Severe central nervous system diseases (other than AD) that affect cognitive function or study compliance. * Severe/unstable systemic diseases (cardiovascular, hepatic, renal, respiratory, endocrine, hematological, psychiatric diseases); life expectancy less than 24 months. * Surgical contraindications: severe coagulation disorders, severe -cardiopulmonary diseases (myocardial infarction/respiratory failure within recent 30 days); severe liver damage (ALT/AST \> 3 times upper limit of normal); severe renal insufficiency (eGFR \< 30ml/min). * Severe primary mental disorders (other than AD) that interfere with efficacy evaluation and cognitive assessment. * History of intracranial hemorrhage or craniocerebral trauma within recent 1 year. * Alcohol or drug abuse/dependence within recent 1 year. * Allergy to indocyanine green, gadolinium contrast agent, 18F-florbetapir or 18F-flortaucipir. * Contraindications for PET examination. * Other conditions judged by investigators unsuitable for enrollment.

Outcomes

Primary Outcomes

Sum of Boxes (CDR-SB) Total Score

The CDR-SB total score ranges from 0 to 18 points. Higher scores indicate more severe cognitive impairment and functional decline. This outcome evaluates the change of total CDR-SB score in patients with severe Alzheimer's disease after receiving deep cervical lymphovenous anastomosis, to assess the therapeutic effect on neurological function.

Time frame: Baseline (pre-operation), 12 months after surgery

Secondary Outcomes

Sum of Boxes (CDR-SB) Total Score

Time frame: Baseline (pre-operation), 1 month and 6 months after surgery

Mini-Mental State Examination (MMSE) Score

MMSE total score ranges from 0 to 30. Higher scores represent better cognitive function. A score below 10 indicates severe cognitive impairment. This measure assesses changes in overall cognitive status after surgical intervention.

Time frame: Baseline (pre-operation), 1 month, 6 months and 12 months after surgery

Zarit Burden Interview (ZBI) Score

ZBI total score ranges from 0 to 88. Higher scores mean heavier caregiver burden. It is used to evaluate the impact of treatment on the psychological and life burden of patients' caregivers.