Brain stimulation timing may shape memory outcomes in Parkinson's patients with GBA1 mutations
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The timing of deep brain stimulation (DBS) surgery is a critical factor in preserving cognitive function for Parkinson's disease patients with a specific genetic mutation, according to a new study by an international team of researchers.
The findings, published in Movement Disorders, offer new guidance for doctors and patients navigating decisions surrounding Parkinson's treatment.
The team was co-led by Dr. Gian Pal, chief of neurology and director of the Movement Disorders Program at Hackensack Meridian Neuroscience Institute at JFK University Medical Center, and associate professor of neurology at the Hackensack Meridian School of Medicine.
Physical relief, cognitive concerns
Deep brain stimulation is a surgical procedure that acts like a pacemaker for the brain, offering relief from disabling tremors, stiffness and involuntary movements when standard medications work unreliably or no longer work.
DBS uses a surgically implanted battery to send steady, mild electrical pulses to the specific areas affected by Parkinson's. These rhythmic pulses act like noise-canceling headphones, overriding the chaotic brain signals that cause tremors and stiffness so patients can move smoothly again.
Patients who carry a mutation in the GBA1 gene—the most common genetic risk factor for Parkinson's disease—often experience significant physical symptoms earlier in life, making them prime candidates for DBS, but are also predisposed to cognitive problems.
Because of their vulnerability to cognitive problems, doctors have started to approach DBS cautiously in people with Parkinson's disease carrying GBA1 mutations. There is a debate over whether GBA1 carriers might face an accelerated loss of memory and executive function (cognitive decline) after undergoing DBS or whether their cognitive problems are a natural part of their disease and unrelated to DBS, making the decision to operate complex.
Surgery timing shapes cognitive risk
To better understand factors that might influence DBS risk in GBA1 carriers, Pal and colleagues wanted to understand how the timing of surgery might affect cognitive outcomes.
Researchers analyzed data from 343 patients across 10 medical centers in the United States and Europe. They compared cognitive outcomes over time between patients with and without the GBA1 mutation who underwent DBS surgery either early or late in the course of their disease.
The research team found that the risk of cognitive decline in genetically predisposed patients is heavily dependent on when the surgery is performed. Patients with the GBA1 mutation who received DBS in the later stages of their disease experienced a significantly faster decline in their cognitive abilities compared with those who received the surgery earlier. In those without the genetic mutation, the timing of DBS did not affect the cognitive outcome.
A seven-to-eight-year window
The study identified a crucial window for intervention. The data showed that the first seven to eight years after a patient's Parkinson's diagnosis represent a vital window for performing DBS.
Intervening before this cutoff allows patients to extend their period of improved physical mobility while also delaying the onset of significant cognitive decline. The severity of the specific genetic mutation a patient carried did not change this overall pattern—timing was the deciding factor.
Genetic testing could guide earlier treatment
This discovery represents a major shift in how neurologists and neurosurgeons might evaluate candidates for DBS. The study's authors emphasize that possessing a GBA1 genetic variant should never disqualify a patient from receiving the life-changing physical benefits of brain surgery. But these additional data can help patients and families better understand the potential benefits and risks of this surgical intervention.
The findings also highlight the critical importance of early genetic testing for Parkinson's patients. By identifying a GBA1 mutation early in the disease process, patients and their care teams can consider DBS as a treatment option sooner rather than later, optimizing both their physical mobility and their long-term mental sharpness.
This new research could pave the way for a more personalized approach to Parkinson's care, in which a patient's unique genetic blueprint directly informs the safest and most effective timeline for their treatment.
"We may be approaching a turning point in how we use deep brain stimulation for Parkinson's disease," said Pal. "For decades, DBS decisions have largely been based on a patient's symptoms and clinical characteristics. Our research suggests that a patient's genetics—and importantly, the timing of surgery—may also matter.
"The future of DBS may not simply be deciding who should receive it, but identifying the right window to intervene for each individual patient. That moves us closer to truly personalized treatment for Parkinson's disease."
More information
Evridiki Asimakidou et al, Timing of Deep Brain Stimulation and Cognitive Trajectories in GBA1‐Associated Parkinson's Disease, Movement Disorders (2026). DOI: 10.1002/mds.70520
Key medical concepts
Parkinson's DiseaseCognitive DeclinesDeep Brain Stimulation
Clinical categories
NeurologyClinical genetics Provided by Hackensack Meridian Health Who's behind this story?
Sadie Harley
BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →
Andrew Zinin
Master's in physics with research experience. Long-time science news enthusiast. Plays key role in Science X's editorial success. Full profile →
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