Cortical hypometabolism and hypoperfusion in Parkinson's disease is extensive: probably even at early disease stages

Recent cerebral blood flow (CBF) and glucose consumption (CMRglc) studies of Parkinson's disease (PD) revealed conflicting results. Using simulated data, we previously demonstrated that the often-reported subcortical hypermetabolism in PD could be explained as an artifact of biased global mean (GM) normalization, and that low-magnitude, extensive cortical hypometabolism is best detected by alternative data-driven normalization methods. Thus, we hypothesized that PD is characterized by extensive cortical hypometabolism but no concurrent widespread subcortical hypermetabolism and tested it on three independent samples of PD patients. We compared SPECT CBF images of 32 early-stage and 33 late-stage PD patients with that of 60 matched controls. We also compared PET FDG images from 23 late-stage PD patients with that of 13 controls. Three different normalization methods were compared: (1) GM normalization, (2) cerebellum normalization, (3) reference cluster normalization (Yakushev et al.). We employed standard voxel-based statistics (fMRIstat) and principal component analysis (SSM). Additionally, we performed a meta-analysis of all quantitative CBF and CMRglc studies in the literature to investigate whether the global mean (GM) values in PD are decreased. Voxel-based analysis with GM normalization and the SSM method performed similarly, i.e., both detected decreases in small cortical clusters and concomitant increases in extensive subcortical regions. Cerebellum normalization revealed more widespread cortical decreases but no subcortical increase. In all comparisons, the Yakushev method detected nearly identical patterns of very extensive cortical hypometabolism. Lastly, the meta-analyses demonstrated that global CBF and CMRglc values are decreased in PD. Based on the results, we conclude that PD most likely has widespread cortical hypometabolism, even at early disease stages. In contrast, extensive subcortical hypermetabolism is probably not a feature of PD.

近期针对帕金森病（PD）的脑血流（CBF）和葡萄糖消耗（CMRglc）研究得出了相互矛盾的结果。我们之前利用模拟数据证明，PD中经常报道的皮质下高代谢现象可解释为有偏差的全局均值（GM）标准化所导致的假象，并且低幅度、广泛的皮质低代谢通过其他数据驱动的标准化方法能更好地被检测出来。因此，我们假设PD的特征是广泛的皮质低代谢，但不存在同时发生的广泛皮质下高代谢，并在三个独立的PD患者样本中进行了验证。我们将32例早期PD患者和33例晚期PD患者的单光子发射计算机断层扫描（SPECT）脑血流图像与60例匹配的对照组进行了比较。我们还将23例晚期PD患者的正电子发射断层扫描（PET）氟脱氧葡萄糖（FDG）图像与13例对照组进行了比较。比较了三种不同的标准化方法：（1）全局均值标准化，（2）小脑标准化，（3）参考簇标准化（雅库舍夫等人提出）。我们采用了标准的基于体素的统计方法（fMRIstat）和主成分分析（SSM）。此外，我们对文献中所有定量的脑血流和葡萄糖消耗研究进行了荟萃分析，以研究PD中的全局均值是否降低。基于体素的分析中，全局均值标准化和主成分分析方法表现相似，即两者都检测到小的皮质簇减少以及广泛的皮质下区域相应增加。小脑标准化显示出更广泛的皮质减少，但皮质下无增加。在所有比较中，雅库舍夫方法检测到几乎相同的非常广泛的皮质低代谢模式。最后，荟萃分析表明PD中的全局脑血流和葡萄糖消耗值是降低的。基于这些结果，我们得出结论：即使在疾病早期，PD很可能具有广泛的皮质低代谢。相反，广泛的皮质下高代谢可能不是PD的特征。