Relative sparing of dopaminergic terminals in the caudate nucleus is a feature of rest tremor in Parkinson’s disease

Abstract Resting tremor (RT) is a Parkinson’s disease (PD) symptom with an unclear relationship to the dopaminergic system. We analysed data from 432 subjects from the Parkinson’s Progression Markers Initiative, 57 additional PD patients and controls and 86 subjects referred for dopamine transporter...

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Main Authors: Marcelo D. Mendonça, Pedro C. Ferreira, Francisco Oliveira, Raquel Barbosa, Bruna Meira, Durval C. Costa, Albino J. Oliveira-Maia, Joaquim Alves da Silva
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:npj Parkinson's Disease
Online Access:https://doi.org/10.1038/s41531-024-00818-8
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author Marcelo D. Mendonça
Pedro C. Ferreira
Francisco Oliveira
Raquel Barbosa
Bruna Meira
Durval C. Costa
Albino J. Oliveira-Maia
Joaquim Alves da Silva
author_facet Marcelo D. Mendonça
Pedro C. Ferreira
Francisco Oliveira
Raquel Barbosa
Bruna Meira
Durval C. Costa
Albino J. Oliveira-Maia
Joaquim Alves da Silva
author_sort Marcelo D. Mendonça
collection DOAJ
description Abstract Resting tremor (RT) is a Parkinson’s disease (PD) symptom with an unclear relationship to the dopaminergic system. We analysed data from 432 subjects from the Parkinson’s Progression Markers Initiative, 57 additional PD patients and controls and 86 subjects referred for dopamine transporter single-photon emission computed tomography (DaT-SPECT). Caudate binding ratio (CBR), but not putamen binding ratio, was higher in RT patients. Furthermore, higher baseline CBR was linked to RT development. In the smaller cohorts, a 4–6 Hz oscillation-based metric from inertial sensors correlated with RT amplitude, distinguished controls from patients with reduced DaT binding and correlated with CBR in the latter group. In silico modelling uncovered that higher CBR in RT patients explained correlations between RT and DaT-SPECT found in several datasets, supporting a spurious origin for ipsilateral correlations between CBR and RT. These results suggest that caudate dopaminergic terminals integrity is a feature of RT with potential pathophysiological implications.
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series npj Parkinson's Disease
spelling doaj-art-cd848a199d944b03840d9dbf48cb87342024-11-24T12:16:07ZengNature Portfolionpj Parkinson's Disease2373-80572024-11-0110111310.1038/s41531-024-00818-8Relative sparing of dopaminergic terminals in the caudate nucleus is a feature of rest tremor in Parkinson’s diseaseMarcelo D. Mendonça0Pedro C. Ferreira1Francisco Oliveira2Raquel Barbosa3Bruna Meira4Durval C. Costa5Albino J. Oliveira-Maia6Joaquim Alves da Silva7Champalimaud Research and Clinical Centre, Champalimaud Foundation, Av. BrasíliaChampalimaud Research and Clinical Centre, Champalimaud Foundation, Av. BrasíliaChampalimaud Research and Clinical Centre, Champalimaud Foundation, Av. BrasíliaDepartment of Clinical Pharmacology and Neurosciences, Parkinson Expert Center, Centre d’Investigation Clinique CIC1436, NeuroToul COEN Center, Toulouse, NS-PARK/FCRIN Network, University Hospital of Toulouse, allée Jean DaussetNeurology Department, Hospital de Egas Moniz, Centro Hospitalar de Lisboa OcidentalChampalimaud Research and Clinical Centre, Champalimaud Foundation, Av. BrasíliaChampalimaud Research and Clinical Centre, Champalimaud Foundation, Av. BrasíliaChampalimaud Research and Clinical Centre, Champalimaud Foundation, Av. BrasíliaAbstract Resting tremor (RT) is a Parkinson’s disease (PD) symptom with an unclear relationship to the dopaminergic system. We analysed data from 432 subjects from the Parkinson’s Progression Markers Initiative, 57 additional PD patients and controls and 86 subjects referred for dopamine transporter single-photon emission computed tomography (DaT-SPECT). Caudate binding ratio (CBR), but not putamen binding ratio, was higher in RT patients. Furthermore, higher baseline CBR was linked to RT development. In the smaller cohorts, a 4–6 Hz oscillation-based metric from inertial sensors correlated with RT amplitude, distinguished controls from patients with reduced DaT binding and correlated with CBR in the latter group. In silico modelling uncovered that higher CBR in RT patients explained correlations between RT and DaT-SPECT found in several datasets, supporting a spurious origin for ipsilateral correlations between CBR and RT. These results suggest that caudate dopaminergic terminals integrity is a feature of RT with potential pathophysiological implications.https://doi.org/10.1038/s41531-024-00818-8
spellingShingle Marcelo D. Mendonça
Pedro C. Ferreira
Francisco Oliveira
Raquel Barbosa
Bruna Meira
Durval C. Costa
Albino J. Oliveira-Maia
Joaquim Alves da Silva
Relative sparing of dopaminergic terminals in the caudate nucleus is a feature of rest tremor in Parkinson’s disease
npj Parkinson's Disease
title Relative sparing of dopaminergic terminals in the caudate nucleus is a feature of rest tremor in Parkinson’s disease
title_full Relative sparing of dopaminergic terminals in the caudate nucleus is a feature of rest tremor in Parkinson’s disease
title_fullStr Relative sparing of dopaminergic terminals in the caudate nucleus is a feature of rest tremor in Parkinson’s disease
title_full_unstemmed Relative sparing of dopaminergic terminals in the caudate nucleus is a feature of rest tremor in Parkinson’s disease
title_short Relative sparing of dopaminergic terminals in the caudate nucleus is a feature of rest tremor in Parkinson’s disease
title_sort relative sparing of dopaminergic terminals in the caudate nucleus is a feature of rest tremor in parkinson s disease
url https://doi.org/10.1038/s41531-024-00818-8
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