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).

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.

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).

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.