Wang Chao, Wang Shuyue, Zhou Cheng, Wu Chenqing, Yang Siyu, Xu Xiaojun, Zhang Minming, Huang Peiyu
Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China.
J Neurol. 2024 Dec 12;272(1):33. doi: 10.1007/s00415-024-12811-5.
Free-water imaging can predict and monitor dopamine system degeneration in patients with Parkinson's disease (PD). However, brain cholinergic function has not been investigated to date in LRRK2 mutation carriers with or without PD using free-water imaging.
To investigate the effect of LRRK2 mutations on the cholinergic system in manifest and premanifest stages of PD using free-water imaging.
We recruited participants from the Parkinson's Progression Markers Initiative (PPMI) data set. We evaluated the effect of LRRK2 mutations on the cholinergic nuclei (i.e., cholinergic nuclei 1, 2, and 3 (Ch123), Ch4, and pedunculopontine nucleus) in manifest and premanifest stages of PD using free-water imaging. We compared free-water values between groups using ANCOVA with adjustment for age. Then, the discriminative power of the free-water content was evaluated by receiver operating characteristic curve (ROC) analysis.
We included 27 patients with LRRK2 PD, 33 LRRK2 mutation carriers without PD, 281 patients with idiopathic PD, and 98 healthy controls. We noted significant between-group differences in free-water content in Ch4 (p = 0.003). LRRK2 mutation carriers without PD had decreased free-water content in the Ch4 compared with healthy controls (p = 0.036) and idiopathic patients with PD (p = 0.001); LRRK2 patients with PD showed decreased tendency of free-water content in the Ch4 compared with idiopathic patients with PD (p = 0.074). Furthermore, ROC analysis showed that free-water content in the Ch4 identified asymptomatic LRRK2 mutation carriers with a high specificity (84.7%).
LRRK2 mutation is associated with decreased free-water content in the Ch4 (also referred to as nucleus basalis of Meynert, nbM), which might suggest early and sustained attempts to compensate for LRRK2-related dysfunction.
自由水成像可预测和监测帕金森病（PD）患者多巴胺系统的退化。然而，迄今为止，尚未使用自由水成像对携带或不携带PD的LRRK2突变携带者的脑胆碱能功能进行研究。
使用自由水成像研究LRRK2突变对PD显性和前驱期胆碱能系统的影响。
我们从帕金森病进展标志物倡议（PPMI）数据集中招募参与者。我们使用自由水成像评估LRRK2突变对PD显性和前驱期胆碱能核（即胆碱能核1、2和3（Ch123）、Ch4和脚桥核）的影响。我们使用协方差分析（ANCOVA）并对年龄进行调整，比较了各组之间的自由水值。然后，通过受试者工作特征曲线（ROC）分析评估自由水含量的判别能力。
我们纳入了27例LRRK2-PD患者、33例不患有PD的LRRK2突变携带者、281例特发性PD患者和98名健康对照者。我们注意到Ch4中自由水含量存在显著的组间差异（p = 0.003）。与健康对照者（p = 0.036）和特发性PD患者（p = 0.001）相比，不患有PD的LRRK2突变携带者Ch4中的自由水含量降低；与特发性PD患者相比，LRRK2-PD患者Ch4中的自由水含量有降低趋势（p = 0.074）。此外，ROC分析表明，Ch4中的自由水含量对无症状LRRK2突变携带者具有较高的特异性（84.7%）。
LRRK2突变与Ch4（也称为Meynert基底核，nbM）中自由水含量降低有关，这可能提示早期且持续地尝试补偿与LRRK2相关的功能障碍。
