Clinical and Dopamine Transporter Imaging Characteristics of Leucine- Rich Repeat Kinase 2 (LRRK2) and Glucosylceramidase Beta (GBA) Parkinson's Disease Participants in the Parkinson's Progression Markers Initiative: A Cross-Sectional Study
Clinical and Dopamine Transporter Imaging Characteristics of Leucine- Rich Repeat Kinase 2 (LRRK2) and Glucosylceramidase Beta (GBA) Parkinson's Disease Participants in the Parkinson's Progression Markers Initiative: A Cross-Sectional Study
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DOI：
10.1002/mds.27989
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发表时间：
2020-02-19
影响因子：
8.6
通讯作者：
Tauscher, Johannes
中科院分区：
文献类型：
--
作者：
Simuni, Tanya;Brumm, Michael C.;Tauscher, Johannes
关于富亮氨酸激酶2 （LRRK2）和糖基神经酰胺酶β (GBA)突变的帕金森病（PD）患者的表型和多巴胺转运体（DAT）成像特征的数据有限。本研究的目的是比较GBA和LRRK2突变携带者早期PD与散发性PD的基线临床和DAT成像特征。帕金森进展标志物计划是一项正在进行的观察性纵向研究，招募了来自全球33个地点的散发性PD、LRRK2和GBA PD携带者。所有参与者每年使用一系列运动和非运动量表、123-I碘氟烷数据成像和生物学变量进行评估。我们评估了158名LRRK2 (89% G2019S)， 80名GBA （89% N370S）和361名散发性PD参与者，平均（标准差）疾病持续时间分别为2.9(1.9),3.1（2.0）和2.6（0.6）年。与散发性PD相比，GBA PD患者在任何运动、认知或自主神经特征上没有差异。LRRK2 PD患者的运动障碍和快速眼动行为障碍问卷得分较低，但在认知和自主功能方面无显著差异。与散发性PD相比，两个遗传组在冲动控制障碍量表上得分更高，但在其他精神特征上没有差异。与散发性PD相比，两个遗传PD组在DAT成像上多巴胺转运体的损失较少。结论：我们证实了先前报道的与LRRK2-PD相关的轻度表型。先前报道的更具侵袭性的GBA-PD表型在n370携带者的疾病早期并不明显。这一观察结果为潜在的疾病改善干预确定了一个窗口。纵向数据对于确定两个遗传队列的进展斜率至关重要。试验注册（NCT01141023）。(c) 2020年国际帕金森和运动障碍学会
Background There are limited data on the phenotypic and dopamine transporter (DAT) imaging characterization of the Parkinson's disease (PD) patients with leucine rich kinase 2 (LRRK2) and glucosylceramidase beta (GBA) mutations.Objective The objective of this study was to examine baseline clinical and DAT imaging characteristics in GBA and LRRK2 mutation carriers with early PD compared with sporadic PD.Methods The Parkinson's Progression Markers Initiative is an ongoing observational longitudinal study that enrolled participants with sporadic PD, LRRK2 and GBA PD carriers from 33 sites worldwide. All participants are assessed annually with a battery of motor and nonmotor scales, 123-I Ioflupane DAT imaging, and biologic variables.Results We assessed 158 LRRK2 (89% G2019S), 80 GBA (89 %N370S), and 361 sporadic PD participants with the mean (standard deviation) disease duration of 2.9 (1.9), 3.1 (2.0), and 2.6 (0.6) years, respectively. When compared with sporadic PD, the GBA PD patients had no difference in any motor, cognitive, or autonomic features. The LRRK2 PD patients had less motor disability and lower rapid eye movement behavior disorder questionnaire scores, but no meaningful difference in cognitive or autonomic features. Both genetic cohorts had a higher score on the impulse control disorders scale when compared with sporadic PD, but no difference in other psychiatric features. Both genetic PD cohorts had less loss of dopamine transporter on DAT imaging when compared with sporadic PD.Conclusions We confirm previous reports of milder phenotype associated with LRRK2-PD. A previously reported more aggressive phenotype in GBA-PD is not evident early in the disease in N370s carriers. This observation identifies a window for potential disease-modifying interventions. Longitudinal data will be essential to define the slope of progression for both genetic cohorts.Trial Registration (NCT01141023). (c) 2020 International Parkinson and Movement Disorder Society