Abstract: Objective To investigate the structural differences of olfactory associated brain areas between patients with Parkinson's disease (PD) and normal controls, and their relationship to olfactory dysfunction by voxel-based morphometry (VBM), and to explore the possibility for early diagnosis. Methods Olfactory detection threshold (DT) and olfactory identification threshold (IT) were determined with "five odors olfactory detection arrays" kit provided by Chinese Academy of Sciences on 26 PD patients, and 26 age and gender matched healthy controls. The relationship between olfactory function and age or duration or severity degree [total Unified Parkinson's Disease Rating Scale (UPDRS) scores] was analysed. The analysis of brain structures were performed at a Siemens 3.0T by using magnetization prepared rapid gradient echo imaging (MPRAGE). The data were processed by using SPM5. Results The olfactory thresholds (DT and IT) of PD patients (0.66 ± 0.84, 2.41 ± 0.74) were significantly higher than those of the controls (-0.64 ± 0.83, 1.08 ± 0.54; Z = 4.455, P = 0.000; t = 4.898, P = 0.000). No significant correlations were seen between olfactory thresholds (DT and IT) and age (DT: rs = 0.199, P = 0.330; IT: rs = 0.256, P = 0.207) or duration (DT: rs = 0.123, P = 0.550; IT: rs = 0.055, P = 0.789) or UPDRS Ⅲ scores (DT: rs = 0.229, P = 0.260; IT: rs = 0.379, P = 0.056) in all PD patients. Compared to controls, significant clusters of increased white matter density were found in bilateral occipital lobes (BA17-19), left posterior cingulate gyrus (BA23, 30, 31) and left paracentral lobule (BA3-5) in PD patients. Significant clusters of increased white matter volume included bilateral occipital lobes (BA17-19), left posterior cingulate gyrus (BA23, 30, 31) and left paracentral lobule (BA3-5). Meanwhile, there were negative relationship between the increase of white matter density in left posterior cingulate gyrus and olfactory IT (rs = 0.496, P = 0.010). Conclusion The olfactory function was found significantly decreased in PD patients, and unrelated to age and duration. Changes of olfactory associated structures, particularly the white matter areas were found by using VBM in early PD with olfactory dysfunction. Our data suggest that early olfactory dysfunction in PD results from changes in the brain areas associated with processing olfaction. VBM can be widely used for the analysis of the diagnosis of PD or neurodegenerative diseases.

Key words: Parkinson disease, Olfaction disorders, Magnetic resonance imaging

摘要： 目的 利用基于体素的形态学分析（VBM）研究原发性帕金森病患者嗅觉相关脑区结构改变及其与嗅觉障碍之间的关系，探讨其作为早期诊断的可能性。方法 应用“五味嗅觉测试液”对26 例诊断明确的早期原发性帕金森病患者进行嗅觉功能检测，并与年龄、病程和病情严重程度［帕金森病统一评价量表（UPDRS）］进行相关分析。磁化准备快速梯度回波序列获取三维结构图像，SPM5 软件后处理，通过配准、分割获得白质密度图像，经调试获得白质体积图像。结果 帕金森病组患者嗅觉察觉阈值和嗅觉识别阈值分别为0.66 ± 0.84 和2.41 ± 0.74，显著高于对照组的-0.64 ± 0.83 和1.08 ± 0.54（Z =4.455，P = 0.000；t = 4.898，P = 0.000）。帕金森病组患者嗅觉功能与年龄（察觉阈值：rs = 0.199，P = 0.330；识别阈值：rs = 0.256，P = 0.207）、病程（察觉阈值：rs = 0.123，P = 0.550；识别阈值：rs = 0.055，P = 0.789）及UPDRSⅢ评分（察觉阈值：rs = 0.229，P = 0.260；识别阈值：rs = 0.379，P = 0.056）无明显相关性；UPDRS 总评分与嗅觉察觉阈值无相关性（rs = 0.314，P = 0.118），但与嗅觉识别阈值呈正相关（rs = 0.397，P = 0.045）。与对照组相比，原发性帕金森病组患者右侧枕叶（BA17 ~ 19 区）、左侧扣带回后部（BA23，30，31 区）、左侧枕叶（BA18，19 区）和左侧中央旁小叶（BA3 ~ 5 区）白质密度，以及双侧枕叶（BA17 ~ 19 区）、左侧扣带回后部（BA23，30，31 区）和左侧中央旁小叶（BA3 ~ 5 区）白质体积均增加，且左侧扣带回后部白质密度增加与嗅觉识别阈值呈负相关（rs =-0.496，P = 0.010）。结论 原发性帕金森病患者嗅觉功能明显减退，但与年龄及病程均无相关性。有嗅觉减退的早期帕金森病患者其嗅觉相关脑区，尤其是神经纤维通过的白质脑区存在明显的病理变化，可能提示帕金森病患者嗅觉障碍是中枢神经变性的结果。与此同时，VBM 法作为一种客观分析方法，弥补了兴趣区分析法的缺点，可以广泛用于帕金森病或神经变性疾病的诊断分析。

关键词: 帕金森病, 嗅觉障碍, 磁共振成像