Objective: To compare motor, cognitive, and medication outcomes following deep brain stimulation (DBS) in Parkinson’s disease patients with GBA1 variants versus non-carriers

Background: Variants in the GBA1 gene are the most common genetic risk factor for Parkinson’s disease (PD) and are associated with faster disease progression and earlier cognitive decline. The impact of GBA1 carrier status on outcomes after DBS remains incompletely understood

Method: This systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to January 2026 for studies reporting DBS outcomes in PD patients stratified by GBA1 carrier status. Random-effects meta-analyses using inverse-variance methods were performed to estimate mean differences (MD) with 95% confidence intervals (CI). Outcomes included changes in UPDRS III (off medication), levodopa equivalent daily dose (LEDD), Mattis Dementia Rating Scale (MDRS), and UPDRS IV at different follow-up intervals.

Results: Thirteen studies including 1,913 patients (424 GBA1 carriers and 1,489 non-carriers) were analyzed. Changes in UPDRS III (off) were similar between GBA1 carriers and non-carriers at 1 year (MD 0.93, 95% CI −1.35 to 3.22), 3 years (MD −1.09, 95% CI −3.03 to 0.86), and 5 years (MD 0.09, 95% CI −4.76 to 4.94). LEDD reduction was also comparable at 1 year (MD 17.60, 95% CI −55.83 to 91.03), 3 years (MD −0.81, 95% CI −50.77 to 49.14), and 5 years (MD −19.68, 95% CI −94.99 to 55.64). In contrast, MDRS scores declined significantly more in GBA1 carriers at 1 year (MD −1.66, 95% CI −2.29 to −1.02), 3 years (MD −3.24, 95% CI −4.75 to −1.73), and 5 years (MD −5.87, 95% CI −8.14 to −3.60). Changes in UPDRS IV at 1 year were not significantly different (MD 0.16, 95% CI −1.07 to 1.39).

Conclusion: DBS provides comparable motor benefit and medication reduction in PD patients regardless of GBA1 carrier status. However, GBA1 carriers demonstrate significantly greater postoperative cognitive decline. These findings suggest that GBA1 status should be considered during DBS candidate evaluation and counselling, with particular attention to preoperative cognitive assessment and long-term monitoring.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/deep-brain-stimulation-outcomes-in-parkinsons-disease-patients-with-gba1-variants-a-systematic-review-and-meta-analysis/