From the Department of Neurology (H.S.Y., H.K.N., S.K., C.H.L.), Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul; Department of Neurology (H.-K.K.), Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine; Department of Radiology (M.P., S.J.A.), and Department of Nuclear Medicine (J.-H.L., Y.H.R.), Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
Neurology. 2024 Dec 24;103(12):e210105. doi: 10.1212/WNL.0000000000210105. Epub 2024 Nov 27.
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.
In this single-site cross-sectional study, we enrolled patients with PD who underwent -(3-[F]fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (F-FP-CIT) PET, F-fluorodeoxyglucose (F-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 F-FP-CIT and F-FDG PET were also enrolled.
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, = 0.025) and directly associated with a higher bradykinesia subscore (β = -0.274, = 0.011). Reduced caudate dopamine was associated with a higher axial subscore (β = -0.125, = 0.004) and lower executive (β = 0.229, = 0.004), visuospatial (β = 0.139, = 0.006), and memory (β = 0.140, = 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.
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.
帕金森病（PD）表现为黑质多巴胺能神经元退化和大脑代谢的特征性变化。然而，它们如何相互关联并影响 PD 患者的运动和认知功能障碍尚未得到很好的阐明。
在这项单中心横断面研究中，我们纳入了接受[3-[F]氟丙基]-2β-羧甲基-3β-[4-碘苯基]去甲托烷（F-FP-CIT）正电子发射断层扫描（PET）、F-氟脱氧葡萄糖（F-FDG）PET、运动障碍协会赞助的统一 PD 评定量表检查和详细神经心理学测试的 PD 患者。实施了一般线性模型和中介分析，以研究纹状体多巴胺转运体可用性、大脑代谢与帕金森运动亚评分或特定领域认知评分之间的关系。还纳入了接受 F-FP-CIT 和 F-FDG PET 的健康对照者（HCs）。
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）表现出相对的大脑高代谢和低代谢，与纹状体多巴胺转运体可用性相关。随着壳核多巴胺转运体可用性的丧失，大脑代谢从旁中央小叶、脑桥和边缘系统相对增加到小脑和前扣带回皮质，而大脑代谢从外侧颞叶和额叶皮质相对减少到枕叶和下顶叶皮质。壳核多巴胺的减少与旁中央小叶相对高代谢有关（中介的标准化间接效应，β=-0.070，p=0.025），并与僵直亚评分较高直接相关（β=-0.274，p=0.011）。尾状核多巴胺的减少与轴性亚评分较高（β=-0.125，p=0.004）和执行功能（β=0.229，p=0.004）、视空间（β=0.139，p=0.006）和记忆（β=0.140，p=0.004）域评分较低有关，通过中介相对脑低代谢。震颤亚评分、语言和注意力评分与纹状体多巴胺可用性或大脑代谢无关。
我们的研究结果表明，在 PD 中，纹状体多巴胺耗竭与大脑代谢改变密切相关，大脑代谢改变根据多巴胺耗竭的程度以特定的空间模式发生，并且根据每个症状的不同，对运动和认知功能障碍有不同的影响。
