Amygdala neurodegeneration: a key driver of visual dysfunction in Parkinson's disease

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dc.contributor.authorErramuzpe Aliaga, Asier
dc.contributor.authorMurueta-Goyena Larrañaga, Ane
dc.contributor.authorJiménez Marín, Antonio
dc.contributor.authorAcera Gil, María Ángeles
dc.contributor.authorTeijeira Portas, Sara
dc.contributor.authorPino, Rocío del
dc.contributor.authorFernández Valle, Tamara
dc.contributor.authorDiez, Ibai
dc.contributor.authorSainz Lugarezaresti, Unai
dc.contributor.authorIbarretxe Bilbao, Naroa
dc.contributor.authorAyala Fernández, Unai
dc.contributor.authorBarrenechea Carrasco, Maitane
dc.contributor.authorCabrera Zubizarreta, Alberto
dc.contributor.authorCortés, Jesús
dc.contributor.authorGómez Esteban, Juan Carlos
dc.contributor.authorGabilondo Cuellar, Iñigo
dc.date.accessioned2025-10-16T14:01:42Z
dc.date.available2025-10-16T14:01:42Z
dc.date.issued2025-02-17
dc.date.updated2025-10-16T14:01:42Z
dc.description.abstractObjective: 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.en
dc.description.sponsorshipThis study was cofunded by the Michael J. Fox Foundation (RRIA [Rapid Response Innovation Awards] 2014 Program, grant ID: 10189), the Carlos III Health Institute, and the European Union (ERDF/ESF, “A Way to Make Europe”/“Investing in Your Future”) through the projects PI14/00679 and PI16/00005; and the Department of Health of the Basque Government through the projects 2016111009 and 2020333033. Iñigo Gabilondo contract was funded by an Ikerbasque Fellow contract from Ikerbasque, the Basque Foundation for Science, and by a Juan Rodes grant JR15/00008 from the Carlos III Health Institute. Asier Erramuzpe contract was funded by The Spanish Ministry of Science and Innovation, grant “RYC2021-032390-I” “RYC2022-035429-I” and Ikerbasque, the Basque Foundation for Science.Antonio Jimenez-Marin contract was funded by a predoctoral grant from the Basque Government “PRE_2019_1_0070”. Jesús Cortés was funded by Ikerbasque, the Basque Foundation for Scienceen
dc.identifier.citationErramuzpe, A., Murueta-Goyena, A., Jimenez-Marin, A., Acera, M., Teijeira-Portas, S., Del Pino, R., Fernández-Valle, T., Diez, I., Sainz-Lugarezaresti, U., Ibarretxe-Bilbao, N., Ayala, U., Barrenechea, M., Cabrera-Zubizarreta, A., Cortés, J., Gómez-Esteban, J. C., & Gabilondo, I. (2025). Amygdala neurodegeneration: a key driver of visual dysfunction in Parkinson's disease. Annals of Clinical and Translational Neurology, 12(4), 768-779. https://doi.org/10.1002/ACN3.70007
dc.identifier.doi10.1002/ACN3.70007
dc.identifier.eissn2328-9503
dc.identifier.urihttps://hdl.handle.net/20.500.14454/3997
dc.language.isoeng
dc.publisherJohn Wiley and Sons Inc
dc.rights© 2025 The Author(s)
dc.subject.otherAmygdala
dc.subject.otherBrain MRI
dc.subject.otherNeurodegeneration
dc.subject.otherRetina
dc.subject.otherVision
dc.titleAmygdala neurodegeneration: a key driver of visual dysfunction in Parkinson's diseaseen
dc.typejournal article
dcterms.accessRightsopen access
oaire.citation.endPage779
oaire.citation.issue4
oaire.citation.startPage768
oaire.citation.titleAnnals of Clinical and Translational Neurology
oaire.citation.volume12
oaire.licenseConditionhttps://creativecommons.org/licenses/by-nc-nd/4.0/
oaire.versionVoR
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