Objective:

To test the hypothesis that striatal dopamine function influences motivational alterations in Parkinson disease (PD), we compared vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DaT) imaging data in PD patients with impulse control disorders (ICDs), apathy, or neither.

Methods:

We extracted striatal binding ratios (SBR) from VMAT2 PET imaging (¹⁸F-AV133) and DaTscans from the Parkinson’s Progression Markers Initiative (PPMI) multicenter observational study. Apathy and ICDs were assessed using the Movement Disorders Society-revised Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP), respectively. We used analysis of variance (ANOVA) and log-linear mixed-effects (LME) regression to model SBRs with neurobehavioral metrics.

Results:

Among 23 participants (mean age 62.7 years, mean disease duration 1.8 years) with VMAT2 imaging data, 5 had apathy, 5 had an ICD, and 13 had neither. ANOVA indicated strong groupwise differences in VMAT2 binding in right anterior putamen [F(2,20) = 16.2, p < 0.0001), right posterior putamen [F(2,20) = 16.9, p < 0.0001), and right caudate [F(2,20) = 6.8, p = 0.006)]. Post-hoc tests and repeated-measures analysis with LME regression also supported right striatal VMAT2 elevation in the ICD group and reduction in the apathy group relative to the group with neither ICD nor apathy. DaT did not exhibit similar correlations, but normalizing VMAT2 with DaT SBR strengthened bidirectional correlations with ICD (high VMAT2/DaT) and apathy (low VMAT2/DaT) in all striatal regions bilaterally.

Conclusions:

Our findings constitute preliminary evidence that striatal presynaptic dopaminergic function helps describe the neurobiological basis of motivational dysregulation in PD, from high in ICDs to low in apathy.

中文翻译：

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帕金森病多巴胺能功能与动机之间的双向相关性

客观的：

为了检验纹状体多巴胺功能影响帕金森病 (PD) 动机改变的假设，我们比较了患有冲动控制障碍 (ICD)、冷漠或两者都不是的 PD 患者的囊泡单胺转运蛋白 2 (VMAT2) 和多巴胺转运蛋白 (DaT) 成像数据。

方法：

^{我们从 VMAT2 PET 成像 ( 18} F-AV133)中提取纹状体结合比 (SBR)，从帕金森病进展标志物计划 (PPMI) 多中心观察研究中提取 DaTscan。冷漠和 ICD 分别使用运动障碍协会修订的统一帕金森病评定量表 (MDS-UPDRS) 和帕金森病冲动强迫症问卷 (QUIP) 进行评估。我们使用方差分析 (ANOVA) 和对数线性混合效应 (LME) 回归来使用神经行为指标对 SBR 进行建模。

结果：

在拥有 VMAT2 影像数据的 23 名参与者（平均年龄 62.7 岁，平均病程 1.8 年）中，5 名患有冷漠症，5 名拥有 ICD，13 名两者都没有。方差分析表明，右前壳核 [F(2,20) = 16.2，p < 0.0001)、右后壳核 [F(2,20) = 16.9，p < 0.0001) 和右尾核 [F] 中 VMAT2 结合存在强烈的分组差异。 (2,20) = 6.8, p = 0.006)]。事后测试和 LME 回归的重复测量分析也支持 ICD 组中右侧纹状体 VMAT2 升高，以及冷漠组相对于既没有 ICD 也没有冷漠的组的减少。DaT 没有表现出类似的相关性，但用 DaT SBR 标准化 VMAT2 增强了所有纹状体区域与 ICD（高 VMAT2/DaT）和冷漠（低 VMAT2/DaT）的双向相关性。

结论：

我们的研究结果构成了初步证据，表明纹状体突触前多巴胺能功能有助于描述 PD 动机失调的神经生物学基础，从 ICD 的高水平到冷漠的低水平。