Distinct serum GDNF coupling with brain structural and functional changes underlies cognitive status in Parkinson's disease

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2023-09-17 DOI:10.1111/cns.14461

Chuanxi Tang, Ruiao Sun, Ke Xue, Mengying Wang, Sijie Liang, Piniel Alphayo Kambey, Mingyu Shi, Changyu Wu, Gang Chen, Dianshuai Gao

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引用次数: 0

Abstract

Aim

Aberrations in brain connections are implicated in the pathogenesis of Parkinson's disease (PD). We previously demonstrated that Glial cell-derived neurotrophic factor (GDNF) reduction is associated with cognition decline. Nonetheless, it is elusive if the pattern of brain topological connectivity differed across PD with divergent serum GDNF levels, and the accompanying profile of cognitive deficits has yet to be determined.

Methods

We collected data on the participants' cognition, demographics, and serum GDNF levels. Participants underwent 3.0T magnetic resonance imaging, and we assessed the degree centrality, brain network topology, and cortical thickness of the healthy control (HC) (n = 25), PD-high-GDNF (n = 19), and PD-low-GDNF (n = 19) groups using graph-theoretic measures of resting-state functional MRI to reveal how much brain connectivity varies and its clinical correlates, as well as to determine factors predicting the cognitive status in PD.

Results

The results show different network properties between groups. Degree centrality abnormalities were found in the right inferior frontal gyrus and right parietal lobe postcentral gyrus, linked with cognition scores. The two aberrant clusters serve as a potentially powerful signal for determining whether a patient has PD and the patient's cognition level after integrating with GDNF, duration, and dopamine dosage. Moreover, we found a significant positive relationship between the thickness of the left caudal middle frontal lobe and a plethora of cognitive domains. Further discriminant analysis revealed that the cortical thickness of this region could distinguish PD patients from healthy controls. The mental state evaluation will also be more precise when paired with GDNF and duration.

Conclusion

Our findings reveal that the topological features of brain networks and cortical thickness are altered in PD patients with cognitive deficits. The above change, accompanied by the serum GDNF, may have merit as a diagnosis marker for PD and, arguably, cognition status.

Abstract Image

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血清 GDNF 与大脑结构和功能变化的不同耦合是帕金森病认知状态的基础。

目的：大脑连接异常与帕金森病（PD）的发病机制有关。我们以前曾证实，胶质细胞源性神经营养因子（GDNF）的减少与认知能力下降有关。然而，血清中 GDNF 水平不同的帕金森病患者的大脑拓扑连接模式是否存在差异，以及随之而来的认知障碍特征是否存在差异，目前尚无定论：我们收集了参与者的认知、人口统计学和血清 GDNF 水平等数据。参试者接受了3.0T磁共振成像，我们利用静态功能磁共振成像的图论测量方法评估了健康对照组（HC）（n = 25）、PD-高GDNF组（n = 19）和PD-低GDNF组（n = 19）的度中心性、大脑网络拓扑结构和皮层厚度，以揭示大脑连通性的变化程度及其临床相关性，并确定预测PD认知状况的因素：结果表明，不同组间的网络特性不同。在右侧额叶下回和右侧顶叶后中央回发现了程度中心性异常，这与认知评分有关。这两个异常集群是判断患者是否患有帕金森氏症以及患者认知水平的潜在有力信号，并与 GDNF、持续时间和多巴胺剂量相结合。此外，我们还发现左侧尾中额叶的厚度与大量认知领域之间存在明显的正相关关系。进一步的判别分析显示，该区域的皮质厚度可将帕金森病患者与健康对照组区分开来。当与 GDNF 和持续时间配对时，精神状态评估也将更加精确：我们的研究结果表明，认知功能障碍的帕金森病患者大脑网络拓扑特征和皮质厚度发生了改变。上述变化与血清 GDNF 相结合，可作为 PD 的诊断标志物，也可作为认知状态的诊断标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.