Combined effects of GBA mutations and STN-DBS negatively impact executive function in Parkinson’s disease
Ahmad Almelegy1, Srujanesh Gunda1, Steve Buyske1, Marc Rosenbaum2, Sepehr Sani2, Mitra Afshari2, Leonard Verhagen Metman2, Christopher Goetz2, Deborah Hall2, M. Mouradian1, Gian Pal1
1Rutgers - Robert Wood Johnson Medical School, 2Rush University Medical Center
Objective:

To determine the specific pattern of cognitive dysfunction in Parkinson’s disease (PD) patients who are glucocerebrosidase mutation carriers (PD-GBA) 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 GBA mutations and STN-DBS negatively impact global cognition. However, the domain-specific pattern of cognitive dysfunction in PD-GBA mutation carriers that drives this cognitive decline remains to be explored.

Design/Methods:
Subjects were examined for mutations in GBA and categorized as GBA carriers with or without DBS (GBA+DBS+, GBA+DBS-), and non-carriers with or without DBS (GBA-DBS+, GBA-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 GBA and DBS status.
Results:

Data were available for 68 subjects (8 GBA+DBS+, 14 GBA+DBS-, 19 GBA-DBS+, and 27 GBA-DBS- subjects).  Performance on the executive function task (Flanker inhibitory control) was significantly lower in GBA+DBS+ subjects vs. the remaining groups (p = 0.007).  After adjusting for covariates, significance was retained when comparing GBA+DBS+ with GBA-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 GBA+DBS+ vs. GBA-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).

Conclusions:

This preliminary study suggests that PD-GBA 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. 

10.1212/WNL.0000000000202514