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

The GBA1 related Parkinson's disease (PD) is associated with more severe non-motor symptoms. To date, studies of the role of GBA1 mutations in the occurrence of impulse control behaviours (ICBs) in PD have yielded controversial results. Our aim was to investigate the frequency and characteristics of ICBs in PD patients with GBA1 mutations.

213 consecutive PD patients were included. Clinical data were gathered via interviews and using the standard set of questionnaires. Genetic analysis of exons 8-11 of the GBA1 gene was performed for all participants.

GBA1 variants were detected in 32 out of 213 patients (GBA-PD). ICBs were more frequent in GBA-PD (31.2%) than in non-mutated PD (nmPD) group (25.9%), though not significantly. Among patients with ICBs and GBA1 variants female sex predominance was observed (60%, p = 0.022). GBA-PD patients with ICBs had a significantly shorter disease and therapy duration, lower total LEDD and QUIP when comparing to nmPD with ICBs. Binary logistic regression showed that age, BDI score, LEDD, and male sex significantly predicted ICBs in the whole sample. In the GBA-PD group, only dopamine agonist use, and a lower UPDRS Part I score were significant predictors.

Dopaminergic treatment is a significant risk factor for ICBs, irrespective of GBA1 mutation status. GBA1 mutations may increase susceptibility to dopaminergic dose-related ICBs adverse effects, particularly in PD patients with fewer non-motor symptoms, and may affect the sex distribution in PD patients with ICBs, potentially attenuating the male predominance.