Subthalamic deep brain stimulation (STN-DBS) is an established therapy for advanced Parkinson’s disease (PD), yet longitudinal cognitive trajectories after surgery (STN-DBS) are highly variable, with a subset of patients (11%) experiencing a multidomain cognitive decline already 6 months after implant. For decades, movement disorders experts struggled to find biomarkers able to reliably predict post-DBS cognitive deterioration.
Recently, a handy hint came from PD genetics. Pal et al. reported that heterozygous GBA1 variant carriers treated with STN-DBS (GBA+DBS+) showed faster cognitive decline on the Mattis Dementia Rating Scale compared to non-carriers receiving DBS (GBA–DBS+) and GBA1 carriers not undergoing surgery (GBA+DBS–) [1]. These findings initially raised major concerns on the indication for DBS in GBA-PD.
However, a large Italian retrospective study (n=365; 73 GBA+DBS+, 292 GBA–DBS+) revealed robust motor improvement and reduced motor complications in GBA+DBS+ patients, despite an increased incidence of dementia at 5 years (25% in GBA+DBS+ vs. 11% in GBA-DBS+) [2]. Expanding the cohort to include also a matched non-operated GBA1 carriers group (76 GBA+DBS) fulfilling DBS eligibility criteria but not operated, showed no significant difference in cognitive trajectories between groups, suggesting DBS itself does not worsen cognition in GBA-PD [3]. Overall, current evidence supports STN-DBS as an effective therapeutic option for GBA-PD. Prospective studies on independent larger cohorts are warranted to better evaluate the role of GBA1 variant classes and different DBS targets (i.e. globus pallidus) on long-term outcomes.
Key Points:
- No biomarkers able to reliably predict cognitive trajectories after STN-DBS implant in PD patients are currently available
- Previous studies suggested that DBS-treated PD patients carrying monoallelic GBA1 variants present a higher risk of cognitive decline than non-operated PD carriers
- Two recent retrospective Italian studies found a sustained motor benefit in DBS-treated GBA-PD and showed that the observed faster cognitive decline in these patients is not affected by DBS
- STN-DBS should be considered a valid and safe therapeutic option for GBA-PD
References:
- Pal G, Mangone G, Hill EJ, et al. Parkinson Disease and Subthalamic Nucleus Deep Brain Stimulation: Cognitive Effects in GBA Mutation Carriers. Ann Neurol. 2022;91(3):424-435. doi:10.1002/ana.26302
- Avenali M, Zangaglia R, Cuconato G, et al. Are patients with GBA-Parkinson disease good candidates for deep brain stimulation? A longitudinal multicentric study on a large Italian cohort. J Neurol Neurosurg Psychiatry. 2024;95(4):309-315. doi:10.1136/jnnp-2023-332387
- Avenali M, Artusi CA, Cilia R, et al. Long-term motor and cognitive outcome of Deep Brain Stimulation in GBA-PD: the Italian PARKNET study. Published online December 28, 2024. doi:10.1101/2024.12.23.24319546
Co-authors:
- Rezzak Yilmaz, Ankara University School of Medicine, Department of Neurology, Ankara, Turkey
- Micol Avenali, Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy; Parkinson's Disease and Movement Disorders Unit, IRCCS Mondino Foundation, Pavia, Italy
Publish on behalf of the Scientific Panel on Movement disorders