Structural and Vascular Alterations of Deep Cervical Lymph Nodes in Amyloid PET-Positive Alzheimer's Disease Patients

• This study is the first to assess deep cervical lymph nodes in Alzheimer’s disease. • High-frequency color Doppler ultrasound revealed distinct lymph node alterations. • Zone 5 nodes in AD were fewer, irregularly shaped, and showed reduced vascularity. • A lymph node–based ultrasound scores distinguished AD from controls with 0.81 AUC. • Findings support lymphatic dysfunction as a novel biomarker in AD pathophysiology. Impaired clearance of brain-derived waste via the glymphatic–lymphatic system has been implicated in Alzheimer’s disease (AD) pathogenesis. Although animal studies highlight the role of deep cervical lymph nodes (dCLNs) in draining brain interstitial solutes, their characteristics in AD patients remain unknown. This study assessed structural and vascular alterations of dCLNs in AD using high-frequency color Doppler ultrasound (HFCDU). Twenty-five patients with amyloid PET–positive AD and 25 age-matched cognitively normal controls underwent HFCDU of dCLNs at neck zone 2–5. Lymph node number, shape, morphology, vascularity (via Superb Microvascular Imaging, SMI), and Solbiati index were quantified. Between-group differences were analyzed using logistic regression and receiver operating characteristic (ROC) analyses, and a simplified diagnostic score was developed from discriminative features. A total of 482 lymph nodes were analyzed (210 from AD, 272 from controls). AD patients had fewer oval-shaped nodes (50% vs. 83%, p<0.001), more irregular morphology (23% vs. 1%, p<0.001), and less distinct internal structure (40% vs. 57%, p<0.001). In Zone 5, they also had fewer nodes (2.4 ± 1.8 vs. 3.8 ± 2.6, p=0.034) and reduced SMI positivity (75% vs. 91%, p=0.006). The count of oval, moderately vascularized (SMI ≤7) nodes in Zone 5 best discriminated AD (AUC=0.79). A composite score integrating these parameters yielded AUC=0.81 (sensitivity 64%, specificity 84%). HFCDU demonstrated distinct morphological and vascular abnormalities of dCLNs in AD, particularly in Zone 5, suggesting impaired lymphatic drainage contributes to AD pathology and supporting lymphatic imaging as a potential biomarker for the failure of lymphatic drainage of the brain.