A team of neuroscientists at the Medical College of Georgia (MCG) at Augusta University has received approval to begin human clinical trials using deep brain stimulation (DBS) as a potential treatment for Alzheimer’s disease. The trial is set to start in January 2026 and will involve six patients aged 65-85 with early-stage Alzheimer’s, who will be recruited from the Wellstar MCG Memory Clinic.
Alzheimer’s disease is responsible for 60-80% of dementia cases worldwide, and its prevalence is expected to nearly double in the United States over the next four decades, according to projections from the National Institute on Aging. Currently, Alzheimer’s ranks as the sixth-leading cause of death in the U.S., based on provisional data from the National Center for Health Statistics.
DBS is a procedure most often used for movement disorders and involves implanting electrodes into specific areas of the brain. These electrodes are connected to a subdermal battery pack that allows neurologists to control nerve signals. The MCG team plans to target the nucleus basalis of Meynert, an area associated with memory and attention.
“The nucleus basalis of Meynert was one of the first sites implicated in Alzheimer’s dementia 50 years ago,” said David T. Blake, PhD, professor in the Neuroscience and Regenerative Medicine department at MCG and principal investigator of the trial. “It declines in function as well as in size as cognitive status declines, and that occurs both with normal aging and, more significantly, with Alzheimer’s dementia. People have looked at this target for many years, and the intermittent stimulation was the first time that we had the capability to lead to cognitive improvement by addressing the nucleus.”
Fernando Vale, MD, chair of MCG’s Neurosurgery department and member of the trial group, described DBS as similar to a pacemaker for brain activity: “We have figured out that if you push the electricity and connections too much, you shut down the system instead of making it better. That’s when Dr. Blake’s idea came to fruition. He came up with the idea of adjusting what we’ve learned in this process, and a simple adjustment can lead to completely different results.”
Vale added: “The idea here is to use brain plasticity, brain recovery, to reconnect and allow the brain to function on a better level for a longer period of time. We’re not claiming that we’re curing – this is not a cure, but if we can delay onset for three, five, seven years, that’s a win-win for everybody. The patient, family and society.”
Blake began his research into DBS for Alzheimer’s ten years ago using monkey models before moving on to other animal studies involving mice. His work showed improvements in working memory after intermittent stimulation sessions targeting relevant brain regions.
“They would touch a touch screen…As we started stimulating them…we found that when we delivered intermittent stimulation…the monkeys would do a little bit better at the task,” Blake recalled.
Further collaboration with Vanderbilt University allowed researchers to monitor changes in cognitive function during these experiments.
“When we stimulate, we cause a dramatic increase in a chemical called acetylcholine…and that leads to large change in blood flow…each time we deliver intermittent stimulation…we get cognitive effects,” Blake explained.
The upcoming human trial will see participants undergo daily 50-minute DBS sessions remotely administered by themselves or caregivers over two years. Six additional patients will serve as controls without receiving DBS; both groups will be assessed regularly throughout this period.
“We’re giving the brain a little interval workout,” said Blake about their approach: “10 seconds of really high activation followed by 40 seconds recovery…repeat for about an hour.”
Vale emphasized rest periods between stimulations were key: “If you don’t rest…in previous DBS investigations…cognitive function was not improving but regressing.”
Eligibility criteria require participants have only Alzheimer-type dementia without major psychiatric illness or significant complications.
“This should be their only dementia…and they shouldn’t have major psychiatric illness,” said Blake.
The main goal is determining whether DBS can sustain or improve cognition over two years: “We want patients to have same clinical dementia ratings or better two years from now as they did when they came into clinic…” said Blake.
If half or more treated patients maintain their baseline cognition after two years—an unusual outcome given typical progression—the team aims for larger multi-site randomized trials leading potentially toward FDA approval.
“Meaning all people who entered trial would get surgery…Half would not get stimulated first six months…then un-blind them after six months…track progress two years,” explained Blake. “If we had good data from that as well—that could lead to FDA approval.”
