Efficacy of Lymphatic-Venous Anastomosis Plus Donepezil Versus Donepezil Alone for Alzheimer's Disease

This study employed a multicenter, randomized controlled trial (RCT) design to evaluatethe efficacy and safety of deep cervical lymphatic/lymph node‐venous anastomosis combinedwith oral donepezil compared to donepezil monotherapy in patients with Alzheimer'sdisease and moderate dementia. Participants were randomized using a central randomizationsystem with stratified block design, with the study center and age group (50‐64 years,65‐80 years) as stratification factors. While study participants and surgicalinvestigators could not be blinded due to the nature of the intervention, efficacyassessors and imaging specialists remained blinded to ensure the objectivity andreliability of the findings. The intervention group received deep cervicallymphatic/lymph node‐venous anastomosis (detailed surgical procedure is specified in theprotocol) in combination with oral donepezil (5‐10 mg/day), while the control groupreceived oral donepezil alone. The total treatment and follow‐up period was 18 months,with assessments conducted at baseline, 1 week, 1, 3, 6, 12, and 18 monthspost‐operation. These included neuropsychological evaluations (MMSE, MoCA, CDR, BADL,IADL, NPI, AES), neuroimaging (MRI, PET, ultrasound), fluid biomarker analyses (CSF andblood levels of Aβ, Tau, neuroinflammatory factors, etc.), and safety monitoring. Theprimary efficacy endpoint was the change in CDR‐SB score at 12 months post‐treatment.Secondary endpoints included changes in multiple cognitive scales, neuroimaging metrics,and biomarkers at 18 months. Safety indicators encompassed adverse event recording, vitalsigns, and laboratory tests.