Yan Jin, Yao Ge
Department of Radiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Neurol. 2025 Jul 23;16:1579561. doi: 10.3389/fneur.2025.1579561. eCollection 2025.
The study aimed to compare the progressive gray matter (GM) atrophy between brain-first and body-first Parkinson's disease (PD) under assumption.
Based on the hypothesis that the timing of rapid eye movement (REM) sleep behavior disorder (RBD) onset relative to motor symptoms may differentiate brain-first from body-first PD subtypes, we stratified PD patients from the Parkinson's Progression Markers Initiative (PPMI) database into 28 RBD-positive PD patients (PDRBD+), 26 RBD-negative PD patients (PDRBD-), 33 isolated RBD (iRBD) patients, and 35 healthy controls. PDRBD+ and PDRBD- groups underwent 4 visits within 48 months including clinical assessments and structure MRI. We measured GM atrophy cross-sectionally and longitudinally and analyzed their associations with other proposed markers.
At baseline, all groups were comparable and showed no significant difference in GM volume (GMV). The longitudinal GMV analysis (group-by-time interaction) showed that, compared with PDRBD- group, PDRBD+ demonstrated significant GM loss in the medial surface of the frontal lobes and the left temporal lobe. In the comparison at the 48th month, besides the bilateral frontotemporal lobes, the PDRBD+ group showed significant GM atrophy in the bilateral cerebellum. The two groups had no significant differences in the 12th and 24th months. Over time, each PD group showed extensive cortical GM loss and bilateral caudate and putamen atrophy. The altered GMV (interaction effect) was positively associated with the MoCA scores and negatively with SCOPA-AUT. Furthermore, the group-level F-statistic map highlighted spatially distinct differences in the protein metabolism, signal transduction, and autophagy pathways between PDRBD+ and PDRBD- groups.
Body-first PD patients show a relatively rapid GMV loss in specific frontotemporal regions (e.g., left middle temporal gyrus) within 6 years following motor symptoms. Our findings add further evidence to the -synuclein spreading hypothesis.
本研究旨在假设条件下比较脑首发和身体首发帕金森病（PD）患者灰质（GM）的进行性萎缩情况。
基于快速眼动（REM）睡眠行为障碍（RBD）发作时间相对于运动症状可能区分脑首发和身体首发PD亚型的假设，我们将帕金森病进展标志物倡议（PPMI）数据库中的PD患者分为28例RBD阳性PD患者（PDRBD+）、26例RBD阴性PD患者（PDRBD-）、33例孤立性RBD（iRBD）患者和35例健康对照。PDRBD+组和PDRBD-组在48个月内接受4次访视，包括临床评估和结构磁共振成像（MRI）。我们对GM萎缩进行横断面和纵向测量，并分析其与其他提出的标志物的关联。
在基线时，所有组具有可比性，GM体积（GMV）无显著差异。纵向GMV分析（组×时间交互作用）显示，与PDRBD-组相比，PDRBD+组在额叶内侧表面和左侧颞叶出现显著的GM丢失。在第48个月的比较中，除双侧额颞叶外，PDRBD+组在双侧小脑也出现显著的GM萎缩。两组在第12个月和第24个月无显著差异。随着时间的推移，每个PD组均出现广泛的皮质GM丢失以及双侧尾状核和壳核萎缩。GMV的改变（交互作用效应）与蒙特利尔认知评估量表（MoCA）评分呈正相关，与帕金森病统一评分量表-自主神经功能部分（SCOPA-AUT）呈负相关。此外，组水平的F统计量图突出显示了PDRBD+组和PDRBD-组在蛋白质代谢、信号转导和自噬途径上的空间差异。
身体首发的PD患者在运动症状出现后的6年内，特定额颞区域（如左侧颞中回）的GMV相对快速丢失。我们的研究结果为α-突触核蛋白传播假说提供了进一步的证据。
