Presynaptic dopaminergic imaging as a neurodegeneration staging biomarker in the alpha-synucleinopathy continuum

To define how dopamine transporter (DaT) SPECT can be used to stage neurodegeneration in neuronal alpha-synucleinopathy patients at the individual level. This is an international multicenter study involving 1067 subjects (mean age 69.8 ± 8.7 years; 63.2% males) who underwent DaT-SPECT as a neurodegeneration biomarker. We enrolled 277 controls, 400 patients with idiopathic/isolated REM sleep behavior disorder (iRBD), representing the prodromal alpha-synucleinopathy stage, and 390 patients with an overt stage, including 175 with overt Parkinson’s disease (oPD) and 215 with overt dementia with Lewy bodies (oDLB). iRBD patients were followed over time and were stratified as non-converters (ncRBD, n = 232) or converters (cRBD, n = 168). The ability of DaT-SPECT to stage the neuronal alpha-synucleinopathy continuum was evaluated using forward stepwise logistic regression models, assuming that this stratification reflects progressive neurodegeneration stages (controls, ncRBD, cRBD, and overt PD/DLB). The combination of the most affected putamen and the least affected caudate best staged patients across the continuum (p < 0.001). Our data suggest that the most affected putamen z-scores can be used to define three levels of neurodegeneration, such as undetected (above − 1), moderate (between − 1 and − 2), and severe (below − 2). Cox regression analysis in iRBD patients showed that these cutoffs predicted phenoconversion (hazard ratios 3.10–5.03), outperforming clinical risk metrics (MDS-UPDRS-III, MMSE, and hyposmia) for overall and motor-predominant phenoconversion. DaT-SPECT z-score thresholds provide a ready-to-use three-tier staging system for alpha-synucleinopathies, enabling objective assessment of neurodegeneration severity and phenoconversion risk at the individual level.

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Publication Details

Journal
European Journal of Nuclear Medicine and Molecular Imaging
Published
2026-04-01
DOI
https://doi.org/10.1007/s00259-026-07834-1
Citations
1
Primary Topic
Parkinson's Disease Mechanisms and Treatments
Type
article
Field-Weighted Citation Impact
22.66

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article

Presynaptic dopaminergic imaging as a neurodegeneration staging biomarker in the alpha-synucleinopathy continuum

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European Journal of Nuclear Medicine and Molecular Imaging
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article

Presynaptic dopaminergic imaging as a neurodegeneration staging biomarker in the alpha-synucleinopathy continuum

David Zogala, Stefano Raffa, Tomoyuki Miyamoto, Karel Šonka, Fabio Pizza, Federico Massa, Alessandra Serra, Valérie Cochen De Cock, Johannes Klein, M. Fernandes, Andrés Perissinotti, Francesco Lanfranchi, Angelica Montini, Frédérik Bes, Jiří Trnka, Irene Bossert, Pietro Mattioli, Toji Miyagawa, Gabriele Arnulfo, Michela Figorilli, Delphine de Verbizier, Aurélien Lathuilière, Agostino Chiaravalloti, Monica Roascio, Silvia Daniela Morbelli, Claudio Liguori, Fabio Placidi, Nicolas Nicastro, Mònica Serradell, Amaia Muñoz-Lopetegi, Aida Niñerola-Baizán, M. Pardini, M. Puligheddu, D. Kunz, B. Orso, V. Garibotto, P. Dušek, Elena Antelmi, Michele Terzaghi, Giuseppe Plazzi, Laura Bonanni, Gerard Mayà, Dario Arnaldi, Masayuki Miyamoto, Val J. Lowe, Bradley F. Boeve, Carles Gaig, Kristína Kulcsárová, Alex Iranzo, Michele T. Hu
article en
1 citations

Abstract

To define how dopamine transporter (DaT) SPECT can be used to stage neurodegeneration in neuronal alpha-synucleinopathy patients at the individual level. This is an international multicenter study involving 1067 subjects (mean age 69.8 ± 8.7 years; 63.2% males) who underwent DaT-SPECT as a neurodegeneration biomarker. We enrolled 277 controls, 400 patients with idiopathic/isolated REM sleep behavior disorder (iRBD), representing the prodromal alpha-synucleinopathy stage, and 390 patients with an overt stage, including 175 with overt Parkinson’s disease (oPD) and 215 with overt dementia with Lewy bodies (oDLB). iRBD patients were followed over time and were stratified as non-converters (ncRBD, n = 232) or converters (cRBD, n = 168). The ability of DaT-SPECT to stage the neuronal alpha-synucleinopathy continuum was evaluated using forward stepwise logistic regression models, assuming that this stratification reflects progressive neurodegeneration stages (controls, ncRBD, cRBD, and overt PD/DLB). The combination of the most affected putamen and the least affected caudate best staged patients across the continuum (p < 0.001). Our data suggest that the most affected putamen z-scores can be used to define three levels of neurodegeneration, such as undetected (above − 1), moderate (between − 1 and − 2), and severe (below − 2). Cox regression analysis in iRBD patients showed that these cutoffs predicted phenoconversion (hazard ratios 3.10–5.03), outperforming clinical risk metrics (MDS-UPDRS-III, MMSE, and hyposmia) for overall and motor-predominant phenoconversion. DaT-SPECT z-score thresholds provide a ready-to-use three-tier staging system for alpha-synucleinopathies, enabling objective assessment of neurodegeneration severity and phenoconversion risk at the individual level.

European Journal of Nuclear Medicine and Molecular Imaging
University of Rome Tor Vergata (IT), University of Verona (IT), University of Modena and Reggio Emilia (IT), University of Cagliari (IT), Université de Montpellier (FR), University of Pavol Jozef Šafárik (SK), Charles University (CZ), University of Pavia (IT), Istituto Giannina Gaslini (IT), Istituto Neurologico Mediterraneo (IT), University of Chieti-Pescara (IT), University of Oxford (GB), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), Istituti Clinici Scientifici Maugeri (IT), Centre Hospitalier Universitaire de Montpellier (FR), Clinique du Millénaire (FR), University Hospital of Geneva (CH), Univerzitná Nemocnica Louisa Pasteura (SK), Hospital Clínic de Barcelona (ES), St. Hedwig-Krankenhaus (DE), Istituto delle Scienze Neurologiche di Bologna (IT), Mayo Clinic in Arizona (US), IMT Mines Alès (FR), Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE), Ospedale Policlinico San Martino (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Social Insurance Saitama Chuo Hospital (JP), General University Hospital in Prague (CZ), EuroMov Digital Health in Motion, University of Turin (IT), Dokkyo Medical University (JP), Charité - Universitätsmedizin Berlin (DE), University of Genoa (IT), University of Bologna (IT)
Università degli Studi di Genova
Openalex Percentile: Top 1%
Parkinson's Disease Mechanisms and Treatments
22.66
DOIOpen Access PDFOpenAlex
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