Tang Chris C, Nakano Yoshikazu, Vo An, Nguyen Nha, Schindlbeck Katharina A, Mattis Paul J, Poston Kathleen L, Gagnon Jean-François, Postuma Ronald B, Niethammer Martin, Ma Yilong, Peng Shichun, Dhawan Vijay, Eidelberg David
Center for Neurosciences, The Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.
Nat Commun. 2024 Dec 30;15(1):10797. doi: 10.1038/s41467-024-54695-z.
Isolated rapid eye movement sleep behavior disorder is a prodrome of α-synucleinopathies. Using positron emission tomography, we assessed changes in Parkinson's disease-related motor and cognitive metabolic networks and caudate/putamen dopaminergic input in a 4-year longitudinal imaging study of 13 male subjects with this disorder. We also correlated times to phenoconversion with baseline network expression in an independent validation sample. Expression values of both Parkinson's disease-related networks increased over time while dopaminergic input gradually declined in the longitudinal cohort. While abnormal functional connections were identified at baseline in both networks, others bridging these networks appeared later. These changes resulted in compromised information flow through the networks years before phenoconversion. We noted an inverse correlation between baseline network expression and times to phenoconversion to Parkinson's disease or dementia with Lewy bodies in the validation sample. Here, we show that the rate of network progression is a useful outcome measure in disease modification trials.
孤立性快速眼动睡眠行为障碍是α-突触核蛋白病的前驱症状。在一项对13名患有该障碍的男性受试者进行的为期4年的纵向成像研究中，我们使用正电子发射断层扫描评估了帕金森病相关运动和认知代谢网络以及尾状核/壳核多巴胺能输入的变化。我们还在一个独立的验证样本中，将出现症状转化的时间与基线网络表达进行了关联。在纵向队列中，帕金森病相关网络的表达值随时间增加，而多巴胺能输入逐渐下降。虽然在两个网络的基线时都发现了异常功能连接，但连接这些网络的其他连接后来才出现。这些变化导致在出现症状转化前数年，网络中的信息流受损。在验证样本中，我们注意到基线网络表达与转化为帕金森病或路易体痴呆的时间呈负相关。在此，我们表明网络进展速率是疾病修饰试验中一个有用的结果指标。
