Objective: To determine specific pattern of cognitive dysfunction in Parkinson’s disease (PD) patients who are glucocerebrosidase mutation carriers (PD-GBA1) compared with non-mutation carriers with and without subthalamic nucleus deep brain stimulation (STN-DBS).

Background: In a previous non-randomized study, we demonstrated that the combined effects of GBA1 mutations and STN-DBS negatively impact global cognition. However, the domain specific pattern of cognitive dysfunction in PD-GBA1 mutation carriers that drives this cognitive decline remains to be explored.

Method: Subjects were examined for mutations in GBA1 and categorized as GBA1 carriers with or without DBS (GBA1+DBS+, GBA1+DBS-), and non-carriers with or without DBS (GBA1-DBS+, GBA1-DBS-). Executive function, processing speed, and episodic memory were examined using the NIH Toolbox. Analysis of variance was used to compare differences in performance on NIH Toolbox measures according to GBA1 and DBS status.

Results: Data were available for 68 subjects (8 GBA1+DBS+, 14 GBA1+DBS-, 19 GBA1-DBS+, and 27 GBA1-DBS- subjects). Performance on the executive function task (Flanker inhibitory control) was significantly lower in GBA1+DBS+ subjects vs. the remaining groups (p = 0.007). After adjusting for covariates, significance was retained when comparing GBA1+DBS+ with GBA1-DBS- subjects (p = 0.013), with a trend towards significance when comparing GBA+DBS+ with the remaining 2 groups (Table 1). Performance on the processing speed task (Pattern Comparison Processing Speed) was significantly lower in the GBA1+DBS+ vs. GBA1-DBS- after adjusting for covariates (p = 0.040). Performance on episodic memory task (Picture Sequence Memory Test) was not significantly different when comparing the 4 groups (p = 0.423).

Conclusion: This preliminary study suggests that PD-GBA1 subjects with STN-DBS may be particularly susceptible to further executive dysfunction due to impaired response inhibition. Larger studies are needed to further investigate this association.

References: Pal, Gian et al. “Parkinson Disease and Subthalamic Nucleus Deep Brain Stimulation: Cognitive Effects in GBA Mutation Carriers.” Annals of neurology vol. 91,3 (2022): 424-435. doi:10.1002/ana.26302

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MDS Abstracts - https://www.mdsabstracts.org/abstract/effects-of-gba1-mutations-and-stn-dbs-on-response-inhibition-in-parkinsons-disease/