Deep Cervical Lymphatic Venous Anastomosis in the Treatment of Alzheimer's Disease (CLEAN-AD Registry)

Alzheimer's Disease (AD) is a common neurodegenerative disorder affecting the elderly population. Global health data estimates that there are 50 million AD patients worldwide, and this number may triple to 150 million cases by 2050. Anti-amyloid β (Aβ) monoclonal antibodies have emerged as disease-modifying therapies for preclinical or mild AD, but the majority of candidate agents have failed to demonstrate clinical efficacy. A series of case studies has suggested the efficacy of deep cervical lymphatic venous anastomosis (DC-LVA) in AD patients, however, there is currently a lack of large-sample cohort study in the real-world.

The primary purpose of this study is to evaluate the efficacy and safety of deep cervical lymphatic venous anastomosis (DC-LVA) in improve the cognitive function of AD patients at 12 months, and to identify subgroups asscociated with the treatment outcome.

This cohort is a multicenter, prospective, registry. A total of 814 patients received DC-LVA treatment in 40 centers from China will be enrolled. Face to face interviews will be made at baseline, 7 days (or hospital discharge), 3 months ± 7 days, 6months ± 15 days, 12 month ± 15 days, 18 month ± 15 days, and 24 month ±15 days.

The change of clinical dementia rating-sum of boxes (CDR-SB) score, Neuropsychiatric Inventory (NPI) score, Activities of Daily Living (ADCS-ADL) score, Caregiver Burden (ZCI-AD) score, Mini-Mental State Examination (MMSE) score, AD Assessment Scale-Cognitive Subscale (ADAS-cog13) score at 3, 6, 12, 18, 24 months, and the change of brain amyloid burden evaluated by Aβ PET-CT centiloid value at 12 months will be measured.

The changes of CDR-SB score will be analyzed using a repeated measures mixed-effects model. Least squares means will be used to estimate the levels at each time point, and the mean difference with 95% confidence intervals will be calculated. Safety outcomes will be summarized using counts/percentages. Adverse events and serious adverse events will be summarized.

In exploratory outcome measures, we will analyse the AD associated biomarkers in lymphatic tissue during the surgery, the change of fluid biomarkers (peripheral blood, saliva, urine,and cerebrospinal fluid AD associated biomarkers), the change of MRI brain volumes (total brain volume, hippocampal volume, lateral ventricle volume), the change of glymphatic function index(DTI-ALPS), the change of MRS metabolic markers (N-Acetylaspartate, Creatine, Choline, Lactate, Glutamate and Glutamine, myo-Inositol), and the change of artificial intelligence-assisted oculomotor/gait measurements during 12 months of follow-up.

• The Change of Clinical Dementia Rating-Sum of Boxes score [Срок оценки: From baseline to 3th, 6th, 18th, 24th months after surgery]
• The Change of Neuropsychiatric Inventory Score [Срок оценки: From baseline to 3th, 6th, 12th,18th, 24th months after surgery]
• The Change of Alzheimer's Disease Assessment Scale-Activity of Daily Living score [Срок оценки: From baseline to 3th, 6th, 12th, 18th, 24th months after surgery]
• The Change of Zarit Caregiver Interview of Alzheimer's Disease Score [Срок оценки: From baseline to 3th, 6th, 12th,18th, 24th months after surgery]
• The Change of Mini-Mental State Examination Score [Срок оценки: From baseline to 3th, 6th, 12th, 18th, 24th months after surgery]
• The Change of Alzheimer's Disease Assessment Scale Cognitive Score [Срок оценки: From baseline to 3th, 6th, 12th,18th, 24th months after surgery]
• The Change of Aβ PET-CT Centiloid value [Срок оценки: From baseline to 12th months after surgery]