Is GBA1 mutation status a game-changer for impulse control behaviour in Parkinson's disease?

Area of Science:

• Neuroscience
• Genetics
• Pharmacology

Background:

• Parkinson's disease (PD) is a neurodegenerative disorder.
• GBA1 gene mutations are linked to PD and associated with non-motor symptoms.
• The role of GBA1 mutations in impulse control behaviors (ICBs) in PD is debated.

Purpose of the Study:

• To determine the frequency and characteristics of ICBs in PD patients with GBA1 mutations.
• To compare ICBs between GBA1-mutated PD (GBA-PD) and non-mutated PD (nmPD) patients.

Main Methods:

• Included 213 consecutive PD patients.
• Collected clinical data through interviews and questionnaires.
• Performed genetic analysis of GBA1 gene exons 8-11.

Main Results:

• GBA1 variants found in 32 patients (GBA-PD).
• ICBs were more frequent in GBA-PD (31.2%) vs. nmPD (25.9%), not statistically significant.
• Female sex predominance observed in GBA-PD patients with ICBs (60%).
• GBA-PD patients with ICBs had shorter disease/therapy duration and lower LEDD/QUIP compared to nmPD with ICBs.
• Logistic regression identified age, BDI score, LEDD, and male sex as predictors in the whole sample.
• In GBA-PD, dopamine agonist use and lower UPDRS Part I score predicted ICBs.

Conclusions:

• Dopaminergic treatment is a significant risk factor for ICBs in PD, irrespective of GBA1 mutation status.
• GBA1 mutations may increase susceptibility to dose-related ICBs from dopaminergic therapy, especially in patients with fewer non-motor symptoms.
• GBA1 mutations might influence the sex distribution of ICBs in PD, potentially reducing male predominance.