A new study suggests an unexpected solution to post-surgical delirium in older adults – gently stimulating a nerve that runs from the brain to nearly every organ in the body.
A team of researchers at the Duke University School of Medicine discovered that activating the vagus system reduced brain inflammation and disruptions in attention and awareness following surgery in mice predisposed to diseases like Alzheimer’s.
The technique, called percutaneous vagus nerve stimulation (pVNS), uses a small, minimally invasive device developed at Duke University to deliver electrical pulses through the skin to stimulate the vagus nerve.
The results challenge the long-held view of delirium as a fleeting side effect of surgery.
Niccolò Terrando is the lead study author and a professor of anaesthesiology and member of the Centre for Translational Pain Medicine at Duke School of Medicine, who has spent years investigating why surgery can so rapidly worsen brain disease in older adults.
He said: ‘Delirium has long been treated as a temporary complication. But for many patients, especially those with underlying neurodegeneration, it can permanently alter the trajectory of the disease.’
To explore the risk, the researchers used mice engineered to develop Alzheimer’s-like pathology. When the animals underwent orthopaedic surgery, the effects on the brain were swift.
Levels of amyloid-beta, the protein that forms plaques in Alzheimer’s disease, spiked. Immune cells in the brain shifted into an inflammatory state. The mice struggled with attention and decision-making tasks that resemble those seen in human delirium.
But when pVNS was applied around the time of surgery, many of those changes were blunted or reversed. Amyloid levels dropped. Neurons were preserved. Brain immune cells near amyloid plaques appeared healthier and more organised.
Most strikingly, the mice performed better on behavioural tests during the critical days immediately after surgery, which is the window when delirium typically appears.
Unlike medications that can broadly suppress the immune system, bioelectronic therapies work by activating specific neural circuits, allowing researchers to fine-tune immune responses rather than shutting them down entirely.
The team also traced the problem to the bloodstream.
They identified interleukin 6, an inflammatory molecule commonly elevated in patients with postoperative delirium, as a key driver of brain inflammation and amyloid disruption.
The FDA already approves vagus nerve stimulation for epilepsy and depression, and earlier this year, it was cleared for use in patients with rheumatoid arthritis who did not respond to medication.
The research is published in Bioelectric Medicine.
