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GBA1突变状态对帕金森病冲动控制行为来说是一个改变局面的因素吗?

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

作者信息

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

机构信息

Neurology Clinic, University Clinical Center of Serbia, Dr Subotića 6, 11000, Belgrade, Serbia.

Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

出版信息

Neurol Sci. 2025 Aug 26. doi: 10.1007/s10072-025-08448-5.

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.

摘要

目的

与GBA1相关的帕金森病(PD)与更严重的非运动症状相关。迄今为止,关于GBA1突变在PD冲动控制行为(ICB)发生中的作用的研究结果存在争议。我们的目的是调查携带GBA1突变的PD患者中ICB的频率和特征。

方法

纳入213例连续的PD患者。通过访谈和使用标准问卷集收集临床数据。对所有参与者进行GBA1基因第8 - 11外显子的基因分析。

结果

213例患者中有32例检测到GBA1变异(GBA - PD)。GBA - PD组中ICB的发生率(31.2%)高于非突变PD(nmPD)组(25.9%),但差异无统计学意义。在有ICB和GBA1变异的患者中,观察到女性占优势(60%,p = 0.022)。与有ICB的nmPD患者相比,有ICB的GBA - PD患者的病程和治疗时间明显更短,总左旋多巴等效剂量(LEDD)和帕金森病统一评分量表(QUIP)更低。二元逻辑回归显示,年龄、贝克抑郁量表(BDI)评分、LEDD和男性性别在整个样本中显著预测ICB。在GBA - PD组中,只有多巴胺激动剂的使用和较低的帕金森病统一评分量表第一部分(UPDRS Part I)得分是显著的预测因素。

结论

无论GBA1突变状态如何,多巴胺能治疗都是ICB的重要危险因素。GBA1突变可能增加对多巴胺能剂量相关ICB不良反应的易感性,特别是在非运动症状较少的PD患者中,并且可能影响有ICB的PD患者的性别分布,潜在地减弱男性优势。

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