Basir Eye Health Research Center, Tehran, Iran.
Neuroimaging Network (NIN), Universal Scientific Education and Research Network (USERN), Children's Medical Center Hospital, Tehran, 14194, Iran.
Brain Imaging Behav. 2019 Feb;13(1):210-219. doi: 10.1007/s11682-017-9781-0.
Olfaction dysfunction is considered as a robust marker of prodromal Parkinson disease (PD). Measurement of olfaction function as a screening test is unsatisfactory due to long lead time interval and low specificity for detection of PD. Use of imaging markers might yield more accurate predictive values and provide bases for combined use of imaging and clinical markers for early PD. Diffusion MRI connectometry was conducted on 85 de novo PD patients in and 36 healthy controls to find: first, white matter tracts with significant difference in quantitative anisotropy between PD groups with various degrees of olfaction dysfunction and second, second fibers with correlation with University of Pennsylvania Smell Identification Test (UPSIT) score in each group using a multiple regression analysis considering age, sex, GDS and MoCA score. Local connectomes were determined in seven of all the possible comparisons, correcting for false discovery rate (FDR). PD patients with anosmia and normal olfaction had the highest number of fibers with decreased connectivity in left inferior longitudinal fasciculus, bilateral fornix, bilateral middle cerebellar peduncle (MCP), bilateral cingulum, bilateral corticospinal tract (CST) and body, genu and splenium of corpus callosum (CC) (FDR = 0.0013). In multiple regression analysis, connectivity in the body, genu and splenium of CC and bilateral fornix had significant negative correlation (FDR between 0.019 and 0.083), and bilateral cingulum and MCP had significant positive correlation (FDR between 0.022 and 0.092) with UPSIT score. White matter connectivity in healthy controls could not be predicted by UPSIT score using the same model. The results of this study provide compelling evidence that microstructural degenerative changes in these areas underlie the clinical phenotype of prodromal olfaction dysfunction in PD and that diffusion parameters of these areas might be able to serve as signature markers for early detection of PD. This is the first report that confirms a discriminative role for UPSIT score in identifying PD specific changes in white matter microstructure. Our results open a window to identify microstructural signatures of prodromal PD in white matter.
嗅觉功能障碍被认为是前驱帕金森病（PD）的一个强有力的标志物。由于潜伏期长和对 PD 的检测特异性低，嗅觉功能测量作为一种筛查试验并不令人满意。使用成像标志物可能会产生更准确的预测值，并为成像和临床标志物联合用于早期 PD 提供依据。对 85 名新发 PD 患者和 36 名健康对照者进行了弥散 MRI 连接测量，以发现：第一，在嗅觉功能障碍程度不同的 PD 组中，有显著差异的白质束的定量各向异性；第二，在考虑年龄、性别、GDS 和 MoCA 评分的多回归分析中，与每组的宾夕法尼亚大学嗅觉识别测试（UPSIT）评分相关的第二纤维。在七种可能的比较中确定了局部连接组，校正了假发现率（FDR）。嗅觉丧失和嗅觉正常的 PD 患者在左侧下纵束、双侧穹窿、双侧小脑上脚（MCP）、双侧扣带回、双侧皮质脊髓束（CST）和体部、膝部和压部胼胝体（CC）的纤维连接减少最多（FDR=0.0013）。在多回归分析中，CC 的体部、膝部和压部以及双侧穹窿的连接与 UPSIT 评分呈显著负相关（FDR 在 0.019 到 0.083 之间），双侧扣带回和 MCP 与 UPSIT 评分呈显著正相关（FDR 在 0.022 到 0.092 之间）。同样的模型不能根据 UPSIT 评分预测健康对照组的白质连接。这项研究的结果提供了令人信服的证据，表明这些区域的微观结构退行性变化是 PD 前驱嗅觉功能障碍临床表型的基础，这些区域的弥散参数可能能够作为 PD 早期检测的特征标志物。这是第一个证实 UPSIT 评分在识别 PD 白质微观结构特异性变化方面具有区分作用的报告。我们的研究结果为识别前驱 PD 的白质微观结构特征标志物打开了一扇窗。
