Neck lymph node removal linked to increased risk of cognitive decline

by Weill Cornell Medical College

edited by Sadie Harley, reviewed by Andrew Zinin

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Surgery to remove lymph nodes in the neck may interfere with cerebrospinal fluid (CSF) drainage from the brain, contributing to cognitive impairment, according to new multicenter research led by Weill Cornell Medicine scientists.

The paper, published in Neuron, found that patients with head and neck cancer who underwent cervical lymphadenectomy, a procedure to remove nearby lymph nodes to reduce cancer spread, had a higher rate of cognitive impairment than the general population.

In preclinical studies, the researchers showed how the procedure can disrupt the brain's waste-clearance system, leading to fluid buildup and a molecular process called oxidative stress that damages cell proteins and triggers inflammation.

"Your body produces lymphatic fluid to wash away waste from every organ, including the brain," said senior author Dr. Laura Santambrogio, professor of radiation oncology and associate director of precision immunology at the Englander Institute of Precision Medicine at Weill Cornell. "If this system is lacking, negative consequences may eventually build up."

Neck lymphedema, or swelling caused by disrupted lymph drainage, is a common complication after lymphadenectomy, said Santambrogio, who is also a professor of biochemistry and biophysics at Weill Cornell. However, this is one of the first papers to fully address what happens when lymphatic fluid cannot be properly cleared from the brain.

Co-first authors Dr. Cristina Clement, an associate professor, and Dr. Zohaib Khan, a research associate, both in radiation oncology at Weill Cornell, helped lead the research.

Patient studies show risk of cognitive impairment

The researchers analyzed records of 1,035 patients who underwent neck lymphadenectomy without additional chemotherapy or radiotherapy at Montefiore Einstein. Rates of cognitive impairment were higher than estimates reported for age-matched populations.

About 18% of patients younger than 65 experienced cognitive impairment within two years after the procedure. In the general population, the overall risk of developing mild-to-severe cognitive impairment in this age group is 4% to 6%.

Among patients older than 65, 25% of the surgery group developed cognitive impairment, compared with 10% to 22% of the general population. While the findings suggest an association between cervical lymphadenectomy and later cognitive impairment, further research is necessary to confirm a direct link.

The researchers also studied a second group of 59 patients who underwent cervical lymphadenectomy without radiation or chemotherapy at the Technical University of Munich.

These patients had brain MRIs before and after their surgeries. The imaging showed accelerated widening of a structure called the ventricular temporal horns after surgery, indicating brain atrophy or shrinkage. This was pronounced when lymph nodes were removed from both sides of the neck.

Potential underlying mechanisms

To uncover the biological mechanisms that might contribute to the observed cognitive decline, researchers conducted studies in animal models. When fluid could no longer drain normally from the brain, they found evidence that brain cells were under increased oxidative stress and that proteins associated with inflammation increased.

The harmful molecular changes appeared after sudden disruption of lymphatic drainage but were not detected when drainage declined gradually in a separate animal model.

The researchers also found that proteins like synapsin, which are involved in relaying signals between neurons, were damaged and clumped together. These dense clumps differed from the plaques of amyloid-beta protein and thin threads of tau protein typically seen in Alzheimer's disease.

Future research

This retrospective study evaluated records of patients who had already received treatment. Next, the researchers plan to conduct a prospective study, which will follow patients over time as they undergo cervical lymph node removal, Santambrogio said.

Surgeons are already exploring ways to improve lymphatic drainage that may one day be applied to those with head and neck cancer at risk for cognitive problems. "Research into transplanting a lymph node from another area of the body may offer a way for lymph fluid that is blocked to enter the venous system and prevent lymphedema," Santambrogio said.

Publication details

Neuron (2026). www.cell.com/neuron/fulltext/S0896-6273(26)00688-4

Journal information: Neuron

Key medical concepts

Cognitive DysfunctionCerebrospinal Fluid LeakOxidative StressBrain atrophy

Clinical categories

NeurologyOncologyGeneral surgeryCommon illnesses & Prevention Provided by Weill Cornell Medical College Who's behind this story?

Sadie Harley

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