孤立性快速眼动睡眠行为障碍患者的大脑嗅觉相关萎缩。
Brain olfactory-related atrophy in isolated rapid eye movement sleep behavior disorder.
机构信息
Department of Neurology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Nuclear Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
出版信息
Ann Clin Transl Neurol. 2023 Dec;10(12):2192-2207. doi: 10.1002/acn3.51905. Epub 2023 Sep 25.
OBJECTIVE
To investigate structural and functional connectivity changes in brain olfactory-related structures in a longitudinal prospective cohort of isolated REM sleep behavior disorder (iRBD) and their clinical correlations, longitudinal evolution, and predictive values for phenoconversion to overt synucleinopathies, especially Lewy body diseases.
METHODS
The cohort included polysomnography-confirmed iRBD patients and controls. Participants underwent baseline assessments including olfactory tests, neuropsychological evaluations, the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, 3T brain MRI, and F-FP-CIT PET scans. Voxel-based morphometry (VBM) was performed to identify regions of atrophy in iRBD, and volumes of relevant olfactory-related regions of interest (ROI) were estimated. Subgroups of patients underwent repeated volumetric MRI and resting-state functional MRI (fMRI) scans after four years.
RESULTS
A total of 51 iRBD patients were included, with 20 of them converting to synucleinopathy (mean time to conversion 3.08 years). Baseline VBM analysis revealed atrophy in the right olfactory cortex and gyrus rectus in iRBD. Subsequent ROI comparisons with controls showed atrophy in the amygdala. These olfactory-related atrophies tended to be associated with worse depression, anxiety, and urinary problems in iRBD. Amygdala F-FP-CIT uptake tended to be reduced in iRBD patients with hyposmia (nonsignificant after multiple comparison correction) and correlated with urinary problems. Resting-state fMRI of 23 patients and 32 controls revealed multiple clusters with aberrant olfactory-related functional connectivity. Hypoconnectivity between the putamen and olfactory cortex was associated with mild parkinsonian signs in iRBD. Longitudinal analysis of volumetric volumetric MRI in 22 iRBD patients demonstrated four-year progression of olfactory-related atrophy. Cox regression analysis revealed that this atrophy significantly predicted phenoconversion.
INTERPRETATION
Progressive atrophy of central olfactory structures may be a potential indicator of Lewy body disease progression in iRBD.
目的
在 REM 睡眠行为障碍（RBD）的孤立纵向前瞻性队列中，研究脑嗅觉相关结构的结构和功能连接变化及其临床相关性、纵向演变以及对Lewy 体病等显性神经突触核病表型转化的预测价值。
方法
该队列纳入了经多导睡眠图（PSG）确诊的 RBD 患者和对照组。参与者接受了基线评估，包括嗅觉测试、神经心理学评估、运动障碍协会统一帕金森病评定量表（MDS-UPDRS）、3T 脑 MRI 和 F-FP-CIT PET 扫描。基于体素的形态学（VBM）用于识别 RBD 中的萎缩区域，并估计相关嗅觉感兴趣区（ROI）的体积。部分患者在四年后接受了重复容积 MRI 和静息状态功能磁共振成像（fMRI）扫描。
结果
共纳入 51 例 RBD 患者，其中 20 例转化为神经突触核病（平均转化时间为 3.08 年）。基线 VBM 分析显示 RBD 中右侧嗅皮质和直回萎缩。与对照组的后续 ROI 比较显示杏仁核萎缩。这些嗅觉相关的萎缩与 RBD 中更严重的抑郁、焦虑和尿失禁问题有关。在嗅觉减退的 RBD 患者中，杏仁核 F-FP-CIT 摄取倾向于减少（经多次比较校正后无统计学意义），并与尿失禁有关。23 例患者和 32 例对照组的静息状态 fMRI 显示多个与嗅觉相关的功能连接异常簇。壳核与嗅皮质之间的连接减少与 RBD 中的轻度帕金森征有关。22 例 RBD 患者的容积 MRI 纵向分析显示，四年来嗅觉相关萎缩进展。Cox 回归分析显示，这种萎缩显著预测了表型转化。
结论
中枢嗅觉结构的进行性萎缩可能是 RBD 中 Lewy 体病进展的潜在指标。
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