Clinical Study on Deep Cervical Lymphatic Trunk Decompression Combined With Mid-Cervical Deep Lymph Node-External Jugular Vein Anastomosis for Alzheimer's Disease Treatment

Prior treatment

• A history of alcohol or drug abuse (other than a history of smoking) in the 2 years prior to the screening visit;
• Presence of any contraindication to MRI, including claustrophobia, or presence of prohibited metallic (ferromagnetic) implants/pacemakers;
• who were currently receiving or had previously received anti-amyloid β disease-modifying therapies (DMTs), or who had participated in clinical trials involving such agents, were not eligible for inclusion.

Other illness

• Dementia caused by other reasons: vascular dementia, central nervous system infections (e.g. HIV, syphilis, etc.), Creutzfeldt-Jakob disease, Huntington's chorea and Parkinson's disease, dementia with Lewy bodies, dementia due to traumatic brain injury, other physical and chemical factors (e.g. drug intoxication, alcohol intoxication, carbon monoxide intoxication, etc.), important physical diseases (e.g. hepatic encephalopathy, pulmonary encephalopathy, etc.), intracranial occupying lesions (e.g. subdural haematoma, brain tumour), endocrine system lesions (e.g. thyroid disease, parathyroid disease), and vitamin deficiency or any other cause of dementia;
• Presence of current serious or unstable medical conditions, including cardiovascular, hepatic, renal, gastrointestinal, respiratory, endocrine, neurological (except for cognitive impairment of AD origin), psychiatric, immunological or haematological disorders, and any other condition which, in the opinion of the investigator, may affect the results of the analyses in this study; or a life expectancy of \<24 months;
• Presence of a history of cancer within 5 years, with the exception of non-metastatic basal cell and/or squamous cell carcinoma of the skin, cervical carcinoma in situ, non-progressive prostate cancer, or other cancers with a low risk of recurrence or spread;
• Subjects with a current diagnosis of any primary psychiatric disorder other than cognitive impairment of AD origin, which requires exclusion if, in the opinion of the Investigator, the presence of the psychiatric disorder or symptom may interfere with interpretation of the effects of the LVA, interfere with cognitive assessment, or interfere with the subject's ability to complete the study. Exclusion is required for subjects with a history of schizophrenia or other chronic psychiatric illness;
• A clinically significant history of multiple or severe drug allergies, significant atopic sensitivities, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme, linear IgA dermatosis, toxic epidermal necrolysis-relaxation, and/or exfoliative dermatitis);
• MRI results at screening that show evidence of significant abnormalities suggesting the presence of another potential etiology of progressive cognitive impairment or the presence of clinically significant findings which may compromise the subject's ability to safely participate in the study. For example, \>2 infarct foci \>2 cm in diameter; infarct foci in key areas such as thalamus, hippocampus, internal olfactory cortex, parafactory cortex, angular gyrus, cortex and other subcortical grey matter nuclei; and a Fazekas Scale grade of \>2 on the Cerebral White Matter Impairment Scale (CWMIS);
• Presence of contraindications to LVA surgery, such as the presence of severe infection at the surgical site, severe cardiac, pulmonary, hepatic, renal, or other systemic functional abnormalities that cannot tolerate general anaesthesia surgery;

Lab values

• Clinically significant abnormalities of clinical significance (as determined by the investigator) on physical or neurological examination, vital signs, ECG, or clinical laboratory findings at screening that may be detrimental to the subject, interfere with the study, or suggest evidence of other causes of dementia;

Other

• Subjects who, in the judgement of the investigator, are actively suicidal and therefore considered to be at significant risk of suicide;
• Illiteracy or insufficient education to complete the scale assessment;
• Currently participating in a clinical trial involving other interventional clinical trials, or participating in any other type of medical research that is considered scientifically or medically incompatible with this study;
• Other reasons that prevent completion of this study: e.g., lack of a stable caregiver;
• Female subjects who are pregnant or planning to become pregnant;
• Patients with a Global Deterioration Scale (GDS) score of 7 were excluded, as the profound loss of verbal communication and basic motor function at this stage precluded adherence to study protocols and reliable participation in postoperative assessments.
• is a member of the Research Centre staff and/or his/her immediate family directly related to this study. Immediate family is defined as a spouse, parent, child, or sibling, whether biologically or legally adopted.

• Age 50-80 years;
• Meet the diagnostic criteria for AD in the Revised Criteria for the Diagnosis and Staging of Alzheimer's Disease (2024) published by the National Institute Aging and Alzheimer's Association (NIA-AA);
• Presence of moderate-to-severe cognitive impairment with a Clinical Dementia Rating (CDR) score ≥2, and Mini-Mental State Examination (MMSE) score of \< 20;
• Stable use of medication for ≥1 month and no planned change in medication within 3 months of randomisation;
• The patients and their families had been informed of the purpose, significance, expected effects and potential risks of the study and voluntarily participated in the study by providing biological samples and signing an informed consent form.