No relevant cognitive sequelae one year after STN-DBS in patients with GBA1-PD - subanalysis of a prospective cohort study

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Abstract Background Heterozygous GBA mutations represent the most common genetic risk factor for Parkinson’s disease (PD) and can be associated with a more aggressive phenotype and an increased risk of cognitive impairment. Although subthalamic nucleus deep brain stimulation (STN-DBS) provides sustained motor benefit, concerns remain regarding its cognitive safety in GBA1-associated PD (GBA1-PD). Objective To investigate the influence of heterozygous GBA1 variants on cognitive outcomes after one year of bilateral STN-DBS in PD. Methods In this subanalysis of a prospective cohort study (NCT03982953), participants underwent comprehensive preoperative and one-year follow-up assessments including clinical, detailed neuropsychological, imaging, and biomarker measures. Genetic testing included GBA sequencing. Propensity score matching was performed to compare GBA1-PD with non-carrier PD (nc-PD) patients according to baseline age, overall cognition and disease severity. Results Of 57 patients receiving STN-DBS, six had heterozygous GBA variants and were matched to six nc-PD patients. Both groups maintained significant motor improvement after one year and neither group showed an overall cognitive decline. At the domain level, GBA1-PD patients performed worse in visual and working memory at baseline and in visual memory and strategy at follow-up. None of the GBA1-PD patients developed postoperative delirium. Conclusions GBA1 variants were not associated with a worse global cognitive outcome one year after STN-DBS. In line with a growing body of evidence, our data suggests that the presence of a GBA1 variant in PD patients is not a strong predictor of the cognitive outcome one year after STN-DBS, irrespective of its severity.

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