Becker-Cohen Michal, Zimran Ari, Dinur Tama, Tiomkin Maayan, Rolfs Arndt, Arkadir David, Bauer Peter, Shulman Elena, Yahalom Gilad, Cohen Mikhal E, Manor Orly, Paltiel Ora, Revel-Vilk Shoshana
Gaucher Unit, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem 9103102, Israel.
Braun School of Public Health and Community Medicine, Hebrew University of Jerusalem, Jerusalem 9124001, Israel.
Life (Basel). 2025 Jun 13;15(6):952. doi: 10.3390/life15060952.
Carriers of Gaucher disease have an increased risk of developing Parkinson's disease (PD). Identifying PD in its prodromal stage is crucial, as early detection before motor symptoms appear allows for potential interventions to salvage neurons and slow or prevent disease progression. At the Gaucher unit at Shaare Zedek Medical Center, we are following a large cohort of obligatory carriers of GBA1 variants (GBA1 carriers) and study ways to identify those at an increased risk for developing PD. In this study, we compared non-invasive prodromal PD tests in 164 GBA1 carriers and 49 participants with no genetic predisposition to PD (controls). The proportion of abnormal tests was compared between groups, and the risk factors for having abnormal tests (at least one or ≥20%) were studied. There were no differences between GBA1 carriers and controls in the frequency of abnormalities, having at least one abnormal test or having ≥20% abnormal tests. Having ≥20% of abnormal tests was associated mainly with age. Principal component analysis identified distinct cognitive, motor, and non-motor dysfunction patterns in GBA1 carriers compared to controls, with cognition in GBA1 carriers more closely linked to motor dysfunction and less influenced by mood and sleep, while in controls, executive function was tied to emotional state and fatigue. Younger carriers outperformed older ones in motor and some cognitive tasks. Those with a family history of PD showed worse cognitive scores than participants with no family history. Sex-based analysis revealed males obtained higher scores in most of the cognition subtests of the NeuroTrax test, whereas it was females in motor and other cognitive domains, mainly in the group of GBA1 carriers. A longitudinal follow-up of GBA1 carriers is ongoing to understand PD progression in GBA1 carriers with the aim of offering targeted intervention for those at higher risk.
戈谢病携带者患帕金森病（PD）的风险增加。在疾病前驱期识别帕金森病至关重要，因为在运动症状出现之前进行早期检测，有可能采取干预措施来挽救神经元，减缓或预防疾病进展。在沙雷兹德克医疗中心的戈谢病诊疗单元，我们正在追踪一大群GBA1变异的 obligatory 携带者（GBA1携带者），并研究识别那些患帕金森病风险增加者的方法。在本研究中，我们比较了164名GBA1携带者和49名无帕金森病遗传易感性的参与者（对照组）的非侵入性前驱期帕金森病检测。比较了两组之间异常检测的比例，并研究了检测异常（至少一项或≥20%）的风险因素。GBA1携带者和对照组在异常频率、至少有一项异常检测或有≥百分之二十异常检测方面没有差异。检测异常≥20%主要与年龄有关。主成分分析确定了与对照组相比，GBA1携带者有不同的认知、运动和非运动功能障碍模式，GBA1携带者的认知与运动功能障碍联系更紧密，受情绪和睡眠影响较小，而在对照组中，执行功能与情绪状态和疲劳相关。年轻携带者在运动和一些认知任务中的表现优于年长携带者。有帕金森病家族史的人认知得分比无家族史的参与者差。基于性别的分析显示，在NeuroTrax测试的大多数认知子测试中，男性得分较高，而在运动和其他认知领域得分较高的是女性，主要是在GBA1携带者组中。对GBA1携带者的纵向随访正在进行中，以了解GBA1携带者帕金森病的进展情况，旨在为高危人群提供有针对性的干预措施。
