前驱表型及早期帕金森病中的边缘系统结构改变与结构协方差

文献信息

中文摘要

背景： 帕金森病（PD）中非运动症状可能先于运动诊断出现，但不同前驱表型是否表现出差异性的边缘系统结构改变尚不清楚。
目的： 探讨由快速眼动睡眠行为障碍（RBD）和/或嗅觉减退定义的前驱PD表型中的边缘系统结构改变。
研究类型： 回顾性横断面研究。
人群/受试者： 315名年龄和性别匹配的参与者（平均年龄=68.34岁；233名男性和82名女性）：健康对照（HC）、无嗅觉减退的前驱RBD、无RBD/梦境演绎行为的嗅觉减退、伴RBD/梦境演绎行为的嗅觉减退，以及未经治疗的PD（每组n=63）。
场强/序列： 3T矢状位T1加权3D MPRAGE或等效序列；标称层厚=1.0 mm；平面内分辨率=1.0×1.0 mm；矩阵=256×256；FOV=256 mm。
评估： 使用FreeSurfer和ScLimbic提取34个边缘系统区域的体积，归一化至估计的总颅内体积，并用ComBat进行协调。
统计检验： 单因素ANCOVA、事后比较、趋势分析、基于秩的偏相关和结构协方差分析。错误发现率（FDR）校正的p<0.05被认为显著。
结果： FDR校正后，显著的组间差异主要见于岛叶（左侧：5.20±1.74、4.64±1.77、4.48±1.50、4.03±1.30、3.92±2.14；右侧：5.26±1.74、4.56±2.00、4.30±1.47、3.95±1.43、3.89±2.36）、眶额皮层（左侧：9.46±2.82、8.48±3.42、7.63±3.17、7.38±3.03、6.63±3.79；右侧：9.37±2.89、8.51±3.33、7.85±3.05、7.16±2.74、6.97±3.89）和左侧海马旁回（1.56±0.77、1.56±0.72、1.29±0.70、1.10±0.59、0.97±1.03）。在探索性表型排序中，最强的负线性趋势见于眶额皮层（左侧：β=-0.319和-0.287；右侧：β=-0.297和-0.266）和左侧海马旁回（β=-0.297和-0.268）。FDR校正后，组内协方差图揭示了涉及嗅觉相关和Papez回路区域的表型特异性显著协方差模式。
数据结论： 边缘系统结构改变在不同前驱表型间存在差异。嗅觉减退相关表型比RBD更广泛地涉及嗅觉相关和Papez回路脑区，而结构协方差模式提示边缘系统结构的表型特异性差异。
证据等级： 3。
技术效能： 阶段2。

英文摘要

BACKGROUND: Non-motor symptoms may precede motor diagnosis in Parkinson's disease (PD), but whether distinct prodromal phenotypes exhibit differential limbic structural alterations remains unclear.
PURPOSE: To investigate limbic structural alterations across prodromal PD phenotypes defined by rapid eye movement sleep behavior disorder (RBD) and/or hyposmia.
STUDY TYPE: Retrospective cross-sectional study.
POPULATION/SUBJECTS: 315 age- and sex-matched participants (mean age = 68.34 years; 233 men and 82 women): healthy controls (HC), prodromal RBD without hyposmia, hyposmia without RBD/dream-enactment behavior, hyposmia with RBD/dream-enactment behavior, and untreated PD (n = 63/group).
FIELD STRENGTH/SEQUENCE: 3T sagittal T1-weighted 3D MPRAGE or equivalent sequences; nominal slice thickness = 1.0 mm; in-plane resolution = 1.0 × 1.0 mm; matrix = 256 × 256; FOV = 256 mm.
ASSESSMENT: Volumes of 34 limbic regions were extracted using FreeSurfer and ScLimbic, normalized to estimated total intracranial volume, and harmonized with ComBat.
STATISTICAL TESTS: One-way ANCOVA, post hoc comparisons, trend analyses, rank-based partial correlations, and structural covariance analyses. False discovery rate (FDR)-adjusted p < 0.05 was considered significant.
RESULTS: After FDR correction, significant group differences were mainly observed in the insula (left: 5.20 ± 1.74, 4.64 ± 1.77, 4.48 ± 1.50, 4.03 ± 1.30, 3.92 ± 2.14; right: 5.26 ± 1.74, 4.56 ± 2.00, 4.30 ± 1.47, 3.95 ± 1.43, 3.89 ± 2.36), orbitofrontal cortex (left: 9.46 ± 2.82, 8.48 ± 3.42, 7.63 ± 3.17, 7.38 ± 3.03, 6.63 ± 3.79; right: 9.37 ± 2.89, 8.51 ± 3.33, 7.85 ± 3.05, 7.16 ± 2.74, 6.97 ± 3.89), and left parahippocampal gyrus (1.56 ± 0.77, 1.56 ± 0.72, 1.29 ± 0.70, 1.10 ± 0.59, 0.97 ± 1.03). Across exploratory phenotype orderings, the strongest negative linear trends were observed in the orbitofrontal cortex (left: β = -0.319 and -0.287; right: β = -0.297 and -0.266), and left parahippocampal gyrus (β = -0.297 and -0.268). Within-group covariance maps revealed phenotype-specific significant covariance patterns involving olfactory-related and Papez circuit regions after FDR correction.
DATA CONCLUSION: Limbic structural alterations differed across prodromal phenotypes. Hyposmia-related phenotypes showed more extensive involvement of olfactory-related and Papez circuit brain regions than RBD, while structural covariance patterns suggest phenotype-specific differences in limbic structures.
EVIDENCE LEVEL: 3.
TECHNICAL EFFICACY: Stage 2.