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不同的神经回路与帕金森病的亚临床神经精神症状相关。

Distinct neural circuits are associated with subclinical neuropsychiatric symptoms in Parkinson's disease.

作者信息

Tinaz Sule, Kamel Serageldin, Aravala Sai S, Sezgin Mine, Elfil Mohamed, Sinha Rajita

机构信息

Yale University School of Medicine, Department of Neurology, Division of Movement Disorders, 15 York St, LCI 710, New Haven, CT 06510, USA; Yale University School of Medicine, Clinical Neurosciences Imaging Center, 789 Howard Ave, New Haven, CT 06519, USA.

Yale University School of Medicine, Department of Neurology, Division of Movement Disorders, 15 York St, LCI 710, New Haven, CT 06510, USA.

出版信息

J Neurol Sci. 2021 Apr 15;423:117365. doi: 10.1016/j.jns.2021.117365. Epub 2021 Feb 21.

Abstract

BACKGROUND

Parkinson's disease (PD) can present with neuropsychiatric symptoms (here, anxiety, depression, and apathy) at any stage of the disease. We investigated the neural correlates of subclinical neuropsychiatric symptoms in relation to motor and cognitive symptoms in a high-functioning PD cohort.

METHODS

Brain morphometry of the cognitively intact, early-stage (Hoehn & Yahr 2) PD group (n = 48) was compared to matched controls (n = 37). Whole-brain, pairwise, resting-state functional connectivity measures were correlated with neuropsychiatric symptom, motor exam, and global cognitive scores of the PD group.

RESULTS

Factor analysis of highly collinear anxiety, depression, and apathy scores revealed a single principal component (i.e., composite neuropsychiatric symptom score) explaining 71.6% of variance. There was no collinearity between the neuropsychiatric, motor, and cognitive scores. Compared to controls, PD group showed only subcortical changes including amygdala and nucleus accumbens atrophy, and greater pallidal volume. Reduced functional connectivity in the limbic cortical-striatal circuits and increased functional connectivity between the cerebellum and occipito-temporal regions were associated with a more impaired neuropsychiatric profile. This functional connectivity pattern was distinct from those associated with motor deficits and global cognitive functioning. The individual components of the neuropsychiatric symptoms also exhibited unique connectivity patterns.

LIMITATIONS

Patients were scanned in "on-medication" state only and a control group with similar neuropsychiatric symptoms was not included.

CONCLUSION

Abnormal functional connectivity of distinct neural circuits is present even at the subclinical stage of neuropsychiatric symptoms in PD. Neuropsychiatric phenotyping is important and may facilitate early interventions to "reorganize" these circuits and delay/prevent clinical symptom onset.

摘要

背景

帕金森病(PD)在疾病的任何阶段都可能出现神经精神症状(此处指焦虑、抑郁和冷漠)。我们在一个功能良好的PD队列中研究了亚临床神经精神症状与运动和认知症状相关的神经关联。

方法

将认知功能完好的早期(Hoehn & Yahr 2级)PD组(n = 48)的脑形态测量结果与匹配的对照组(n = 37)进行比较。对PD组的全脑、成对、静息态功能连接测量结果与神经精神症状、运动检查和整体认知评分进行相关性分析。

结果

对高度共线性的焦虑、抑郁和冷漠评分进行因子分析,发现一个单一主成分(即综合神经精神症状评分)解释了71.6%的方差。神经精神、运动和认知评分之间不存在共线性。与对照组相比,PD组仅表现出皮质下变化,包括杏仁核和伏隔核萎缩,以及苍白球体积增大。边缘皮质-纹状体回路功能连接减少以及小脑与枕颞区之间功能连接增加与更严重的神经精神症状相关。这种功能连接模式与运动缺陷和整体认知功能相关的模式不同。神经精神症状的各个成分也表现出独特的连接模式。

局限性

仅在“服药”状态下对患者进行扫描,且未纳入具有相似神经精神症状的对照组。

结论

即使在PD神经精神症状的亚临床阶段,不同神经回路的功能连接也存在异常。神经精神表型分析很重要,可能有助于早期干预以“重组”这些回路并延迟/预防临床症状的出现。

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