Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
J Parkinsons Dis. 2022;12(8):2493-2506. doi: 10.3233/JPD-223489.
Cholinergic degeneration is strongly associated with cognitive decline in patients with Parkinson's disease (PD) but may also cause motor symptoms and olfactory dysfunction. Regional differences are striking and may reflect different PD related symptoms and disease progression patterns.
To map and quantify the regional cerebral cholinergic alterations in non-demented PD patients.
We included 15 non-demented PD patients in early-moderate disease stage and 15 age- and sex-matched healthy controls for [18F]FEOBV positron emission tomography imaging. We quantitated regional variations using VOI-based analyses which were supported by a vertex-wise cluster analysis. Correlations between imaging data and clinical and neuropsychological data were explored.
We found significantly decreased [18F]FEOBV uptake in global neocortex (38%, p = 0.0002). The most severe reductions were seen in occipital and posterior temporo-parietal regions (p < 0.0001). The vertex-wise cluster analysis corroborated these findings. All subcortical structures showed modest non-significant reductions. Motor symptoms (postural instability and gait difficulty) and cognition (executive function and composite z-score) correlated with regional [18F]FEOBV uptake (thalamus and cingulate cortex/insula/hippocampus, respectively), but the correlations were not statistically significant after multiple comparison correction. A strong correlation was found between interhemispheric [18F]FEOBV asymmetry, and motor symptom asymmetry of the extremities (r = 0.84, p = 0.0001).
Cortical cholinergic degeneration is prominent in non-demented PD patients, but more subtle in subcortical structures. Regional differences suggest uneven involvement of cholinergic nuclei in the brain and may represent a window to follow disease progression. The correlation between asymmetric motor symptoms and neocortical [18F]FEOBV asymmetry indicates that unilateral cholinergic degeneration parallels ipsilateral dopaminergic degeneration.
胆碱能退化与帕金森病（PD）患者的认知能力下降密切相关，但也可能导致运动症状和嗅觉功能障碍。区域差异显著，可能反映了不同的 PD 相关症状和疾病进展模式。
绘制和量化非痴呆型 PD 患者的区域性大脑胆碱能变化。
我们纳入了 15 名处于早期-中度疾病阶段的非痴呆型 PD 患者和 15 名年龄和性别匹配的健康对照者进行[18F]FE-OBV 正电子发射断层扫描成像。我们使用基于 VOI 的分析方法来定量区域性变化，并通过顶点聚类分析进行支持。探索了成像数据与临床和神经心理学数据之间的相关性。
我们发现全局新皮层的[18F]FE-OBV 摄取明显减少（38%，p=0.0002）。枕叶和后颞顶叶区域的减少最为严重（p<0.0001）。顶点聚类分析证实了这些发现。所有皮质下结构均显示适度但无统计学意义的减少。运动症状（姿势不稳和步态困难）和认知（执行功能和综合 z 评分）与区域性[18F]FE-OBV 摄取相关（丘脑和扣带皮层/岛叶/海马体），但在经过多次比较校正后，相关性没有统计学意义。还发现了大脑半球间[18F]FE-OBV 不对称性与肢体运动症状不对称之间的强烈相关性（r=0.84，p=0.0001）。
非痴呆型 PD 患者的皮质胆碱能退化明显，但皮质下结构更为微妙。区域性差异表明胆碱能核团的不均匀参与，可能代表了观察疾病进展的窗口。不对称性运动症状与新皮层[18F]FE-OBV 不对称之间的相关性表明，单侧胆碱能退化与同侧多巴胺能退化平行。
