Potential Role of Lymphovenous Bypass in Mitigating Alzheimer's Disease Dementia

Abstract

This case report explores the therapeutic potential of lymphovenous bypass (LVB) surgery performed at the neck in neurodegenerative diseases, specifically Alzheimer's disease (AD) dementia. The subject is a 58-year-old woman who was previously healthy but began experiencing unexplained memory decline and frequent disorientation in the past 7 years, leading to an AD diagnosis. Despite ongoing pharmaceutical therapy, her symptoms progressed to severe dementia accompanied by behavioral and psychological symptoms of dementia (BPSD). Her Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores were both 0/30, and ¹⁸ F-AV-45 PET/CT revealed abnormal brain amyloid load. For salvage therapy, she underwent LVBs on her neck bilaterally. Postoperatively, she got better MMSE and MoCA scores with dramatic improvement in communication and activity. ¹⁸ F-AV-45 PET/CT scans 4 months after surgery indicated a reduction in abnormal brain amyloid deposits. This case report highlights the potential effectiveness of LVB surgery in reducing brain amyloid load and attenuating cognitive impairment and BPSD. Further research with animal experiments and clinical trials is necessary to confirm these findings.

Keywords: Alzheimer's disease; behavioral and psychological symptoms; brain lymphatics; dementia; lymphovenous bypass.

Fig. 1

The ¹⁸ F-AV-45 PET/CT, a medical imaging technique used to detect amyloid plaques in the brain, a hallmark of Alzheimer's disease, confirmed an abnormal brain amyloid load. Preoperative 4-year scan (upper row) and postoperative 4-month scan (lower row).

Fig. 2

Using ultrasound mapping, we preoperatively marked the sternocleidomastoid (SCM) muscle, external jugular vein (EJV), accessory nerve (AN), and lymph nodes (left side). Indocyanine green (ICG) was injected cranially along the carotid sheath (white star) to trace the lymphatic channels and confirm their patency following lymphovenous bypass.

Fig. 3

The lymphovenous bypass at the neck was performed by making a longitudinal incision on the external jugular vein (EJV; white arrowhead; left). Lymphatic channels, confirmed with Indocyanine green (ICG) enhancement, were connected to the EJV under a microscope by “octopus” technique (middle). Anastomosis (black arrowhead) was accomplished with a patency check (right). Lymphatic channels (black arrow) and the EJV distal to the anastomosis (white arrow) showed ICG signal, while the cranial EJV was not enhanced (white star).

Fig. 4

The pathologically enlarged lymph node (black star) and the branch vein of external jugular vein (EJV) were dissected (above forceps) for lymph node-to-vein anastomosis (LNVA).

Fig. 5

Pathohistological examination of neck lymph nodes showed HE stains, TDP-43, amyloid-β (Aβ), phosphorylated tau (p-tau) (dementia proteins), α-synuclein (pathological factor). TDP-43, transactive response DNA binding protein 43.