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. 2025 Aug 26.
doi: 10.1007/s10072-025-08448-5. Online ahead of print.

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

Nikola Kresojević #  1   2 , Vladana Marković #  3   4 , Cveta Geratović  4 , Milica Ječmenica Lukić  3   4 , Aleksandra Tomić  3   4 , Valerija Dobričić  3   5 , Iva Stanković  3   4 , Tanja Stojković  3   4 , Nataša Dragašević  3   4 , Maksim Šarčević  3 , Milena Janković  3   4 , Ana Marjanović  3   4 , Ivana Novaković  4 , Vladimir Kostić  3   4 , Marina Svetel  3   4 , Igor Petrović  3   4
Affiliations

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

Nikola Kresojević et al. Neurol Sci. .

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: GBA1 mutation; Impulse control behaviours; Parkinson’s disease.

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Conflict of interest statement

Declarations. Conflicts of interest: The authors declare that there are no conflicts of interest relevant to this work. Ethical standard and Informed consent: The Ethics Committee of the Medical Faculty, University of Belgrade approved the study. All participants signed an informed consent to participate in the study. All procedures performed were in accordance with the ethical standards of the institutional committee and with the 1975 Helsinki declaration and its later amendments. Disclosures: Nikola Kresojević received speaking honoraria for Salveo, Makpharm and Remedica and support for attending meetings and/or travel from Salveo and INO Pharm. Vladana Marković received speaking honoraria from Makpharm, Remedica and Uni-chem, and support for attending meetings and/or travel from Medtronic and Boston scientific. Milica Ječmenica Lukić received speaking honoraria from Makpharm and Uni-chem. Aleksandra Tomić received speaking honoraria from Salveo, Remedica, Makpharm, Uni-chem and support for attending meetings and/or travel from Medtronic. Nataša Dragašević received speaking honoraria from Salveo, Makpharm, Uni-chem and support for attending meetings and/or travel from Boston scientific and Godwill Pharma. Marina Svetel received speaking honoraria from Makpharm and Uni-chem. Igor Petrović received speaking honoraria from Salveo, Makpharm, Uni-chem and support for attending meetings and/or travel from Medtronic and Boston scientific. Cveta Geratović, Valerija Dobričić, Iva Stanković, Tanja Stojković, Milena Janković, Ana Marjanović, Maksim Šarčević, Ivana Novaković and Vladimir Kostić report no conflict of interest. Non-financial interest: Iva Stanković is a MSA mission research steering council member and the chair of MDS-ES Education Committee.

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