Short- and Long-term Impact of Deep Brain Stimulation on Motor and Cognitive Outcomes in GBA vs. Non-gba Parkinson's Disease: A Meta-analysis

Introduction: Deep brain stimulation (DBS) is a widely used treatment for managing Parkinson's disease symptoms, yet its impact on disease progression in patients with glucocerebrosidase (GBA) mutations versus those without remains uncertain. This study aims to evaluate the short- and long-term clinical outcomes of patients with Parkinson’s disease carrying GBA mutations compared to non-carriers following DBS.

Methods: A systematic search of published studies was conducte until September 18, 2024, including studies that reported clinical outcomes for patients with and without GBA mutations who had undergone DBS surgery, with a follow-up period of at least one year. The outcomes of interest included Unified Parkinson's Disease Rating Scale, Part III (MDS-UPDRS-III) for motor symptoms, the Levodopa Equivalent Daily Dose (LEDD), and the Mattis Dementia Rating Scale (MDRS) for cognitive decline.

Results: Of the initial 1195 articles, 5 cohorts and 2 case-control studies met our inclusion criteria, considering 985 patients for analysis, of whom 222 were GBA mutation carriers. The analysis of OFF med UPDRS-III and LEDD revealed that patients experienced overall improvements at one and five years post-DBS, regardless of the presence of GBA mutations. However, cognitive assessments revealed significant cognitive decline, with a MDRS mean difference of 8.42 (95% CI: 4.04–12.80, p< 0.0002) at five years, with GBA carriers experiencing a more pronounced decline (p < 0.0001, I² = 93.7%).

Conclusion : In patients with GBA mutation, deep brain stimulation demonstrates a heightened risk of cognitive decline over five years compared to non-carriers, while showing a similar response in MDS-UPDRS-III and LEDD reduction.