Institute of Biomedical Engineering, Bogazici University, Istanbul, Turkey.
Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
J Neural Transm (Vienna). 2020 Sep;127(9):1285-1294. doi: 10.1007/s00702-020-02227-6. Epub 2020 Jul 6.
Parkinson's disease (PD) with mild cognitive impairment (PD-MCI) is currently diagnosed based on an arbitrarily predefined standard deviation of neuropsychological test scores, and more objective biomarkers for PD-MCI diagnosis are needed. The purpose of this study was to define possible brain perfusion-based biomarkers of not only mild cognitive impairment, but also risky gene carriers in PD using arterial spin labeling magnetic resonance imaging (ASL-MRI). Fifteen healthy controls (HC), 26 cognitively normal PD (PD-CN), and 27 PD-MCI subjects participated in this study. ASL-MRI data were acquired by signal targeting with alternating radio-frequency labeling with Look-Locker sequence at 3 T. Single nucleotide polymorphism genotyping for rs9468 [microtubule-associated protein tau (MAPT) H1/H1 versus H1/H2 haplotype] was performed using a Stratagene Mx3005p real-time polymerase chain-reaction system (Agilent Technologies, USA). There were 15 subjects with MAPT H1/H1 and 11 subjects with MAPT H1/H2 within PD-MCI, and 33 subjects with MAPT H1/H1 and 19 subjects with MAPT H1/H2 within all PD. Voxel-wise differences of cerebral blood flow (CBF) values between HC, PD-CN and PD-MCI were assessed by one-way analysis of variance followed by pairwise post hoc comparisons. Further, the subgroup of PD patients carrying the risky MAPT H1/H1 haplotype was compared with noncarriers (MAPT H1/H2 haplotype) in terms of CBF by a two-sample t test. A pattern that could be summarized as "posterior hypoperfusion" (PH) differentiated the PD-MCI group from the HC group with an accuracy of 92.6% (sensitivity = 93%, specificity = 93%). Additionally, the PD patients with MAPT H1/H1 haplotype had decreased perfusion than the ones with H1/H2 haplotype at the posterior areas of the visual network (VN), default mode network (DMN), and dorsal attention network (DAN). The PH-type pattern in ASL-MRI could be employed as a biomarker of both current cognitive impairment and future cognitive decline in PD.
帕金森病伴轻度认知障碍（PD-MCI）目前是基于神经心理学测试评分的任意预定义标准差来诊断的，需要更客观的 PD-MCI 诊断生物标志物。本研究旨在使用动脉自旋标记磁共振成像（ASL-MRI）定义不仅轻度认知障碍，而且 PD 风险基因携带者的可能脑灌注生物标志物。15 名健康对照（HC）、26 名认知正常的帕金森病（PD-CN）和 27 名 PD-MCI 患者参与了这项研究。ASL-MRI 数据通过使用 Look-Locker 序列的交替射频标记信号靶向在 3T 下采集。使用 Stratagene Mx3005p 实时聚合酶链反应系统（美国安捷伦科技公司）对 rs9468[微管相关蛋白 tau（MAPT）H1/H1 与 H1/H2 单倍型]进行单核苷酸多态性基因分型。PD-MCI 中有 15 名患者携带 MAPT H1/H1，11 名患者携带 MAPT H1/H2，所有 PD 中有 33 名患者携带 MAPT H1/H1，19 名患者携带 MAPT H1/H2。通过单因素方差分析评估 HC、PD-CN 和 PD-MCI 之间脑血流（CBF）值的体素差异，然后进行两两事后比较。进一步，通过两样本 t 检验比较携带风险 MAPT H1/H1 单倍型的 PD 患者与非携带者（MAPT H1/H2 单倍型）的 CBF。一种可以概括为“后叶灌注不足”（PH）的模式将 PD-MCI 组与 HC 组区分开来，准确率为 92.6%（敏感性=93%，特异性=93%）。此外，携带 MAPT H1/H1 单倍型的 PD 患者在视觉网络（VN）、默认模式网络（DMN）和背侧注意网络（DAN）的后叶区域的灌注量低于携带 H1/H2 单倍型的患者。ASL-MRI 中的 PH 型模式可作为 PD 目前认知障碍和未来认知衰退的生物标志物。
