BACKGROUND AND OBJECTIVES Parkinson disease (PD) shows degeneration of dopaminergic neurons in the substantia nigra and characteristic changes in brain metabolism. However, how they correlated and affect motor and cognitive dysfunction in PD has not yet been well elucidated. METHODS In this single-site cross-sectional study, we enrolled patients with PD who underwent N-(3-[18F]fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (18F-FP-CIT) PET, 18F-fluorodeoxyglucose (18F-FDG) PET, the Movement Disorder Society-sponsored Unified PD Rating Scale examination, and detailed neuropsychological testing. General linear models and mediation analyses were implemented to investigate the association between striatal dopamine transporter availability, brain metabolism, and parkinsonian motor subscores or domain-specific cognitive scores. Healthy controls (HCs) who underwent 18F-FP-CIT and 18F-FDG PET were also enrolled. RESULTS Compared with HCs (n = 38, mean age 67.3 ± 5.9 years; 19 women), patients with PD (n = 143, mean age 69.0 ± 9.0 years; 69 women) characteristically showed relative brain hypermetabolism and hypometabolism that correlated with striatal dopamine transporter availability. As the loss of putaminal dopamine transporter availability increased, brain metabolism relatively increased from the paracentral lobule, pons, and limbic system to the cerebellum and anterior cingulate cortex, whereas brain metabolism relatively decreased from the lateral temporal and frontal cortices to the occipital and inferior parietal cortices. Reduced putaminal dopamine was associated with a higher rigidity subscore by the mediation of relative hypermetabolism in the paracentral lobule (standardized indirect effect, β = -0.070, p = 0.025) and directly associated with a higher bradykinesia subscore (β = -0.274, p = 0.011). Reduced caudate dopamine was associated with a higher axial subscore (β = -0.125, p = 0.004) and lower executive (β = 0.229, p = 0.004), visuospatial (β = 0.139, p = 0.006), and memory (β = 0.140, p = 0.004) domain scores by the mediation of relative brain hypometabolism. The tremor subscore and language and attention scores were not associated with striatal dopamine availability or brain metabolism. DISCUSSION Our findings suggest that in PD, striatal dopamine depletion and altered brain metabolism are closely linked, that changes in brain metabolism occur in specific spatial patterns depending on the degree of dopamine depletion, and that both differentially affect motor and cognitive dysfunction depending on each symptom.

中文翻译：

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纹状体多巴胺耗竭和脑代谢变化与帕金森病患者运动和认知缺陷的关联。


背景和目的 帕金森病 （PD） 显示黑质中多巴胺能神经元的变性和脑代谢的特征性变化。然而，它们如何关联和影响 PD 中的运动和认知功能障碍尚未得到很好的阐明。方法 在这项单中心横断面研究中，我们招募了接受 N-（3-[18F]氟丙基）-2β-碳甲氧基-3β-（4-碘苯基）去甲烷 （18F-FP-CIT） PET、18F-氟脱氧葡萄糖 （18F-FDG） PET、运动障碍协会赞助的统一 PD 评定量表检查和详细的神经心理学测试的 PD 患者。实施一般线性模型和中介分析以研究纹状体多巴胺转运蛋白可用性、脑代谢和帕金森病运动子评分或特定领域认知评分之间的关联。还纳入了接受 18F-FP-CIT 和 18F-FDG PET 的健康对照 （HCs）。结果 与 HCs （n = 38，平均年龄 67.3 ± 5.9 岁;19 名女性） 相比，PD 患者 （n = 143，平均年龄 69.0 ± 9.0 岁;69 名女性）特征性地表现出与纹状体多巴胺转运蛋白可用性相关的相对脑代谢亢进和代谢减退。随着壳核多巴胺转运蛋白可用性的丧失增加，从中央旁小叶、脑桥和边缘系统到小脑和前扣带皮层的脑代谢相对增加，而从外侧颞叶和额叶皮层到枕骨和下顶叶皮层的脑代谢相对减少。壳核多巴胺减少与通过介导副中央小叶中相对代谢亢进的较高刚性子评分相关（标准化间接效应，β = -0.070，p = 0。025） 并与较高的运动迟缓子评分直接相关 （β = -0.274，p = 0.011）。尾状状多巴胺降低与较高的轴向子评分 （β = -0.125，p = 0.004） 和较低的执行 （β = 0.229，p = 0.004）、视觉空间 （β = 0.139，p = 0.006） 和记忆 （β = 0.140，p = 0.004） 域评分相关通过相对脑代谢减退的介导。震颤分项评分以及语言和注意力评分与纹状体多巴胺可用性或脑代谢无关。讨论 我们的研究结果表明，在 PD 中，纹状体多巴胺消耗和脑代谢改变密切相关，脑代谢的变化发生在特定的空间模式中，具体取决于多巴胺消耗的程度，并且两者都根据每种症状对运动和认知功能障碍产生不同的影响。