Amygdala Neurodegeneration: A Key Driver of Visual Dysfunction in Parkinson's Disease

IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Annals of Clinical and Translational Neurology Pub Date : 2025-02-17 DOI:10.1002/acn3.70007
Asier Erramuzpe, Ane Murueta-Goyena, Antonio Jimenez-Marin, Marian Acera, Sara Teijeira-Portas, Rocío Del Pino, Tamara Fernández-Valle, Ibai Diez, Unai Sainz-Lugarezaresti, Naroa Ibarretxe-Bilbao, Unai Ayala, Maitane Barrenechea, Alberto Cabrera-Zubizarreta, Jesús Cortés, Juan Carlos Gómez-Esteban, Iñigo Gabilondo
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Abstract

Objective

Visual disability in Parkinson's disease (PD) is not fully explained by retinal neurodegeneration. We aimed to delineate the brain substrate of visual dysfunction in PD and its association with retinal thickness.

Methods

Forty-two PD patients and 29 controls underwent 3-Tesla MRI, retinal spectral-domain optical coherence tomography, and visual testing across four domains. Voxel-level associations between gray matter volume and visual outcomes were used to define a visual impairment region (visualROI). Functional connectivity of the visualROI with brain networks was analyzed. Covariance analysis of brain regions associated with retinal thinning (retinalROI) was conducted using hierarchical clustering to develop a model of retinal and brain neurodegeneration linked to disease progression.

Results

The amygdala was the primary component of the visualROI, comprising 32.3% and 14.6% of its left and right volumes. Functional connectivity analysis revealed significant disruptions between the visualROI and medial/lateral visual networks in PD. Covariance analysis identified three clusters within retinalROI: (1) the thalamic nucleus, (2) the amygdala and lateral/occipital visual regions, and (3) frontal regions, including the anterior cingulate cortex and frontal attention networks. Hierarchical clustering suggested a two-phase progression: early amygdala damage (Braak 1–3) disrupting visual network connections, followed by retinal and frontal atrophy (Braak 4–5) exacerbating visual dysfunction.

Interpretation

Our findings support a novel, amygdala-centric two-phase model of visual dysfunction in PD. Early amygdala degeneration disrupts visual pathways, while advanced-stage disconnection between the amygdala and frontal regions and retinal neurodegeneration contributes to further visual disability.

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杏仁核神经变性:帕金森病视觉功能障碍的关键驱动因素。
目的:视网膜神经退行性变不能完全解释帕金森病(PD)的视力障碍。我们的目的是描述PD患者视觉功能障碍的脑底物及其与视网膜厚度的关系。方法:42例PD患者和29例对照者进行了3-特斯拉MRI、视网膜光谱域光学相干断层扫描和四个域的视觉测试。灰质体积和视觉结果之间的体素级关联被用来定义视觉损伤区域(visualROI)。分析了视觉感兴趣区与脑网络的功能连通性。使用分层聚类对与视网膜变薄相关的脑区域(retinalROI)进行协方差分析,以建立与疾病进展相关的视网膜和脑神经变性模型。结果:杏仁核是视觉roi的主要组成部分,分别占其左右体积的32.3%和14.6%。功能连通性分析显示,PD患者的视觉roi和内侧/外侧视觉网络之间存在明显的中断。协方差分析确定了视网膜roi中的三个集群:(1)丘脑核,(2)杏仁核和外侧/枕部视觉区,以及(3)额叶区域,包括前扣带皮层和额叶注意网络。分层聚类提示两阶段进展:早期杏仁核损伤(Braak 1-3)破坏视觉网络连接,随后视网膜和额叶萎缩(Braak 4-5)加剧视觉功能障碍。解释:我们的研究结果支持一种新的、以杏仁核为中心的PD视觉功能障碍两期模型。早期杏仁核变性破坏视觉通路,而晚期杏仁核与额叶区和视网膜神经变性之间的连接断开会导致进一步的视觉障碍。
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来源期刊
Annals of Clinical and Translational Neurology
Annals of Clinical and Translational Neurology Medicine-Neurology (clinical)
CiteScore
9.10
自引率
1.90%
发文量
218
审稿时长
8 weeks
期刊介绍: Annals of Clinical and Translational Neurology is a peer-reviewed journal for rapid dissemination of high-quality research related to all areas of neurology. The journal publishes original research and scholarly reviews focused on the mechanisms and treatments of diseases of the nervous system; high-impact topics in neurologic education; and other topics of interest to the clinical neuroscience community.
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