Objective: To describe the motor and non-motor response in PD Patients Carrying The GBA Gene Variant under treatment with DBS

Background: Parkinson’s disease (PD) patients carrying the GBA gene variant may be more likely to experience cognitive decline or dementia in the early stages of the disease compared to other forms of PD. This makes it difficult to treat motor symptoms with deep brain stimulation (DBS) when motor complications arise despite medication adjustments; Additionally, it is relevant to assess other non-motor symptoms in the long term

Method: From our database of over 600 patients treated with DBS, we conducted a retrospective study of 17 PD patients carrying the GBA gene including the Colombian variant (k198e); 9 of them (5 women and 4 men) received deep brain stimulation (DBS) in the subthalamic nucleus.

Results: The age range of the patients treated with DBS was 44 to 72 years, with a median age of 56 years. After a follow-up of 24 to 60 months, a significant improvement was observed on the UPDRS motor scale (55%), as well as a reduction in the dopa equivalent dose (60%).Three patients had cognitive problems before DBS implantation, particularly executive dysfunction, and two of them had mild memory impairment. Seven patients had moderate to severe anxiety and depression before and after DBS implantation, requiring continuous medication, with good response to antidepressive-anxiolitic medications.

Conclusion: Patients with Parkinson’s disease who carry the GBA gene respond very well to DBS treatment with regard to motor symptoms. While cognitive impairment is one of the most important aspects, affective disorders, especially anxiety, must also be considered. Although we know the specific mutation type in each patient, longer-term studies are needed to fully evaluate the impact.

References: 1. Avenali M, Artusi CA, Cilia R, Italian PARKNET Study Group; Valente EM. Long-Term Motor and Cognitive Outcome of Deep Brain Stimulation in Patients With Parkinson Disease With a GBA1 Pathogenic Variant. Neurology. 2025 Nov 11;105(9):e214036. doi: 10.1212/WNL.0000000000214036. Epub 2025 Oct 22. PMID: 41124650; PMCID: PMC12549006.
2. Mangone G, Bekadar S, Cormier-Dequaire F, Tahiri K, Welaratne A, Czernecki V, Pineau F, Karachi C, Castrioto A, Durif F, Tranchant C, Devos D, Thobois S, Meissner WG, Navarro MS, Cornu P, Lesage S, Brice A, Welter ML, Corvol JC; contributors/investigators. Early cognitive decline after bilateral subthalamic deep brain stimulation in Parkinson’s disease patients with GBA mutations. Parkinsonism Relat Disord. 2020 Jul;76:56-62. doi: 10.1016/j.parkreldis.2020.04.002. Epub 2020 Jun 9. PMID: 32866938.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/deep-brain-stimulation-dbs-for-parkinsons-disease-pd-patients-carrying-the-gba-gene-variant-greater-than-expected-benefits-similar-cognitive-decline-but-caution-is-advised-regarding-anxiety-a/