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Timing of Deep Brain Stimulation and Cognitive Trajectories in GBA1-associated Parkinson’s Disease

E. Asimakidou, M. Avenali, J. O. Aasly, M. Afshari, R. Alcalay, S. Anderson, CA. Artusi, B. Bernard, M. Bozzali, S. Bressman, G. Calandra-Buonaura, F. Cavallieri, R. Cilia, JC. Corvol, A. Cocco, RMA. de Bie, D. Ehrlich, R. Eleopra, G. Pal, EM. Valente (Cambridge, United Kingdom)

Meeting: 2026 International Congress

Keywords: Cognitive dysfunction, Deep brain stimulation (DBS), Parkinson’s

Category: Parkinson's Disease: Surgical Therapy

Objective: This study focuses on the timing of DBS in relation to PD onset and explores cognitive trajectories across different GBA1 variant classes, with a level of temporal resolution and stratification that has not been previously reported.

Background: Individuals with Parkinson’s disease (PD) carrying GBA1 variants often develop advanced motor complications that prompt evaluation for Deep Brain Stimulation (DBS). However, concerns about accelerated cognitive decline after DBS in GBA1 carriers complicate clinical decision-making. A critical aspect that is increasingly gaining attention is the time at which DBS is performed.

Method: A multi-center cohort study across 10 study sites in Europe and USA was conducted. The study population comprised subjects with (GBA-PD) and without GBA1 variants (nonGBA-PD), who were subjected to bilateral subthalamic nucleus (STN)-DBS. The main outcome measure was the Mattis Dementia Rating Scale (MDRS).

Results: A total of 343 individuals (91 GBA-PD and 242 nonGBA-PD) were included in this study. Percentile-based stratification into early and late DBS treatment groups revealed that GBA-PD patients who underwent DBS treatment at later stages after PD onset had the worst cognitive outcome among all groups with a significantly faster rate of cognitive decline  compared to GBA-PD subjected to DBS at earlier time-points. Importantly, we observed a negative correlation between MDRS and the time elapsed until DBS treatment, which was borderline statistically significant in GBA-PD but not in nonGBA-PD.   Cognitive trajectories were markedly worse in the GBA-PD compared to nonGBA-PD, and this pattern was not influenced by variant type.

Conclusion: DBS treatment at an earlier time-point after disease onset may prolong the duration of improved motor function and reduced pharmacological requirements before marked cognitive decline emerges in GBA-PD.

To cite this abstract in AMA style:

E. Asimakidou, M. Avenali, J. O. Aasly, M. Afshari, R. Alcalay, S. Anderson, CA. Artusi, B. Bernard, M. Bozzali, S. Bressman, G. Calandra-Buonaura, F. Cavallieri, R. Cilia, JC. Corvol, A. Cocco, RMA. de Bie, D. Ehrlich, R. Eleopra, G. Pal, EM. Valente. Timing of Deep Brain Stimulation and Cognitive Trajectories in GBA1-associated Parkinson’s Disease [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/timing-of-deep-brain-stimulation-and-cognitive-trajectories-in-gba1-associated-parkinsons-disease/. Accessed October 1, 2026.
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