A nerve-based approach to helping older adults bounce back after surgery

After surgery, some older adults don’t simply recover — they unravel. Confusion, inattention, and agitation can set in, a condition known as postoperative delirium.  

For patients already living with Alzheimer’s disease and other forms of dementia, the episode can mark a turning point, accelerating long-term cognitive decline. Despite its prevalence, there are no FDA-approved treatments to prevent delirium after surgery.  

A new Duke University School of Medicine study suggests an unexpected solution: gently stimulating a nerve that runs from the brain to nearly every organ in the body.  

A team of researchers discovered that activating the vagus system — a major communication highway linking the brain, immune system, and internal organs — reduced brain inflammation and disruptions in attention and awareness following surgery in mice predisposed to Alzheimer’s-like disease.  

The technique, called percutaneous vagus nerve stimulation, or pVNS, uses a small, minimally invasive device developed at Duke University to send 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.

“Delirium has long been treated as a temporary complication," said lead study author Niccolò Terrando, PhD, a professor of anesthesiology and member of the Center 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.  

“But for many patients, especially those with underlying neurodegeneration, it can permanently alter the trajectory of the disease,” he said.   

To explore the risk, the researchers used mice engineered to develop Alzheimer’s-like pathology. When the animals underwent orthopedic 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 human delirium.  

But when pVNS — a technology developed by a team of Duke scientists and engineers including Terrando, and study co-author Warren Grill, PhD, a professor of biomedical engineering at Duke Pratt School of Engineering — 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 organized.  

Most strikingly, the mice performed better on behavioral 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.  

In lab experiments, IL-6 damaged the brain’s protective blood vessels and promoted toxic protein buildup, effects that vagus nerve stimulation appeared to counteract. 

Protection at a critical point 

The findings help explain a familiar but poorly understood experience: the older relative who “isn’t the same” after an operation. 

“Our study gives those stories a biological foundation and suggests a way forward,” said Terrando.  

Vagus nerve stimulation is already approved by the FDA 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 National Institutes of Health and the Alzheimer’s Association supported the recent study and clinical trials in surgical patients are underway.  

“Bioelectronic approaches offer new ways to modulate inflammation across the body,” Terrando said, “and that could have real implications for preventing neurological complications like delirium.” 

Shantell Kirkendoll is a senior science writer and managing editor in the Office of Strategic Communications at Duke University School of Medicine. 

Main photo by Jack Newman.