Summary:
A multicenter international study finds that the timing of Deep Brain Stimulation (DBS) is the key factor in preserving cognition for Parkinson’s disease patients who carry a GBA1 mutation. Published in Movement Disorders, the analysis of 343 patients from 10 academic centers identified a critical surgical window of roughly seven to eight years after diagnosis. When DBS was performed before that cutoff, GBA1 carriers achieved substantial motor benefits while delaying serious cognitive decline. In contrast, patients who had DBS later in their disease course experienced faster and more pronounced deterioration in memory and executive function.
Key Facts:
- The GBA1 Timing Window: Parkinson’s patients with a GBA1 mutation who received DBS within seven to eight years of symptom onset maintained cognitive function significantly longer than those who had surgery later.
- Genetics-Specific Vulnerability: This timing effect was specific to GBA1 carriers; patients without the mutation showed no difference in cognitive outcomes based on DBS timing.
- Case for Early Genetic Screening: A positive GBA1 result should not exclude candidates from DBS. Instead, early genetic testing can help clinicians schedule surgery within the window that best protects cognition.
Source: Hackensack Meridian Health
Deep Brain Stimulation (DBS) has transformed the management of advanced Parkinson’s disease. Thin electrodes are implanted in targeted motor areas of the brain and connected to a subcutaneous neurostimulator that delivers controlled electrical pulses. This neuromodulation reduces the abnormal neural firing that causes tremor, stiffness and dyskinesias, offering sustained motor control when medications alone are insufficient.
However, treating patients with pathogenic variants in the GBA1 gene—currently the most common genetic risk factor for Parkinson’s—raises complex clinical questions.
People with GBA1-associated Parkinson’s often develop motor complications earlier and more aggressively, making them strong candidates for DBS. At the same time, they carry an elevated risk for earlier and more severe cognitive impairment and dementia.
That combination has driven debate: does DBS itself worsen cognitive decline in GBA1 carriers, or is dementia an inevitable consequence of the genetic disease course? The new international study offers clarity: DBS does not inherently speed cognitive decline, but the timing of the procedure is crucial.
Reported in the peer-reviewed journal Movement Disorders, the study shows that DBS performed within a defined early window can preserve cognitive function while delivering lasting motor benefits.
“We may be approaching a turning point in how we use deep brain stimulation for Parkinson’s disease,” said co-lead author Gian Pal, M.D., Chief of Neurology and Director of the Movement Disorders Program at Hackensack Meridian Neuroscience Institute at JFK University Medical Center. “Historically, decisions about DBS were driven mainly by symptoms and clinical features. Our findings indicate that genetics—and importantly, when surgery is done—also matter. The future of DBS may be less about who should get it and more about finding the right time for each patient. That brings us closer to truly personalized care for Parkinson’s disease.”
Tracking Long-Term Outcomes Across 10 Centers
To answer the timing question, Dr. Pal and an international team pooled longitudinal clinical and cognitive data from 343 Parkinson’s patients treated at 10 major academic centers across the United States and Europe. Participants were grouped by GBA1 carrier status and by whether they received DBS earlier or later in their disease course.
The analysis uncovered a clear pattern:
- Late-Stage DBS in GBA1 Carriers: GBA1 carriers who delayed DBS until later stages experienced a distinctly faster decline in cognitive measures after surgery, particularly in memory and executive functioning.
- Early-Stage DBS in GBA1 Carriers: Carriers who underwent DBS earlier preserved cognitive function for a longer period while achieving meaningful, sustained motor improvement.
- Non-Carriers (Sporadic Parkinson’s): In patients without GBA1 variants, the timing of DBS showed no measurable effect on long-term cognitive trajectories, indicating the timing vulnerability is specific to the GBA1 genotype.
The 7–8 Year Window: Timing Matters More Than Variant Severity
The investigators identified an actionable clinical threshold: receiving DBS within seven to eight years after Parkinson’s diagnosis emerged as the critical window for preserving cognition in GBA1 carriers. Statistical analyses showed this threshold consistently separated better from worse cognitive outcomes in carriers.
Importantly, the study found that the severity class of the GBA1 variant (milder versus more severe enzymatic impairment) did not change this relationship. In other words, timing of the intervention was the dominant factor determining cognitive preservation, regardless of variant class.
The authors emphasize that a positive GBA1 test should not serve as a reason to deny DBS. Rather, it should prompt timely planning so patients can access neuromodulation benefits before irreversible cognitive decline begins.
These results support a case for routine early genetic testing in newly diagnosed Parkinson’s patients. Knowing GBA1 status at the outset enables clinicians to integrate genetic risk into surgical planning and to recommend DBS within an optimal time window when appropriate.
Funding: This research was supported by a grant from the Italian Ministry of Health under the Next Generation EU Program—Piano Nazionale di Ripresa e Resilienza (PNRR)—Mission 6C2–2.1, plus funding from the Parkinson Disease Foundation and the National Institute of Neurological Disorders and Stroke (K23-NS097625-05). Additional collection and institutional support included U01-NS094148-01, U01-NS107016-01A1, ANR-10-IAIHU-06, and NIH intramural funding from the National Institute of Neurological Disorders and Stroke.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The full journal paper was reviewed.
- Additional context was added by our staff.
About this Neurology and Neuropharmacology Research:
- Media Contact: Seth Augenstein
- Source: Hackensack Meridian Health
- Image Credit: Image credited to Neuroscience News
- Original Research (Open Access): Movement Disorders (Oct 1, 2026). Title: “Timing of Deep Brain Stimulation and Cognitive Trajectories in GBA1-Associated Parkinson’s Disease.” Authors include Evridiki Asimakidou MD, Micol Avenali MD, Jan O. Aasly MD, Mitra Afshari MD, Roy N. Alcalay MD, and many others in the PARKNET Study Group.
- DOI: 10.1002/mds.70520
Abstract
Timing of Deep Brain Stimulation and Cognitive Trajectories in GBA1-Associated Parkinson’s Disease
Background
People with Parkinson’s who carry GBA1 variants frequently develop motor complications that lead to consideration of DBS. Concerns about whether DBS accelerates cognitive decline in these patients complicate clinical decisions. The timing of DBS relative to disease onset is increasingly recognized as a key variable.
Objective
This study aimed to determine how the timing of DBS after Parkinson’s onset affects cognitive trajectories, comparing different GBA1 variant classes and patients without GBA1 variants.
Methods
A multicenter cohort study across 10 sites in Europe and the USA enrolled patients with and without GBA1 variants who underwent bilateral subthalamic nucleus (STN) DBS. The primary cognitive outcome was the Mattis Dementia Rating Scale (MDRS).
Results
Among 343 participants (91 with GBA1-associated Parkinson’s and 252 without the variant), percentile-based grouping into early and late STN-DBS and linear mixed-model analyses showed that GBA1 patients who received DBS later had significantly faster cognitive decline, independent of age. Sensitivity analyses identified seven- and eight-year cutoffs as distinguishing early from late DBS in GBA1 patients. A negative correlation between MDRS scores and time to DBS was present in GBA1 carriers but not in non-carriers, and cognitive trajectories were generally worse in GBA1 patients regardless of variant class.
Conclusions
For patients with GBA1-associated Parkinson’s, STN-DBS performed at later stages is linked to a higher risk of cognitive decline. Earlier intervention may prolong the period of improved motor function before significant cognitive impairment emerges. These results underscore the potential value of early genetic testing and consideration of disease duration when planning STN-DBS in genetically defined Parkinson’s populations.
