Data-driven trajectories of atrophy explain clinical heterogeneity across Lewy body diseases.
Overview
and 10 other authors
Dag Aarsland9,20, Eric Westman6,21, Daniel Ferreira6,22, Glenda Halliday2,23, Simon J.G. Lewis3, Rimona S. Weil18,24, Ramon Landin-Romero2,25, Christian Lambert26, Neil P. Oxtoby4,5, Elie Matar1,2,2727 affiliations
- Central Clinical School, Faculty of Medicine and Health, University of Sydney, Australia
- Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Australia
- Parkinson's Disease Research Centre, Macquarie Medical School, Macquarie University, Australia
- UCL Hawkes Institute, University College London, 90 High Holborn, London WC1V 6LJ, UK
- UCL Department of Computer Science, University College London, 66–72 Gower Street, London WC1E 6EA, UK
- Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Center for Alzheimer Research, Karolinska Institutet, Blickagången 16, Huddinge, Stockholm 141 52, Sweden
- Department of Clinical Medicine, University of Bergen, Postboks 7804, Bergen 5020, Norway
- Centre for Age-Related Medicine (SESAM), Stavanger University Hospital, Postboks 8100, Stavanger 4068, Norway
- Translational and Clinical Research Institute, Campus for Ageing and Vitality, Newcastle Upon Tyne NE4 5PL, UK
- Sant Pau Memory Unit, IR SANT PAU, Hospital de la Santa Creu i Sant Pau, 167 Sant Antoni Maria Clare, Barcelona 08025, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), 5 Valderrebollo Street, Madrid 28031, Spain
- Neurology and Geriatrics Department, Brugmann University Hospital, Université Libre De Bruxelles, Place Arthur Van Gehuchten 4, Brussels 1020, Belgium
- Unit for Brain Aging and Dementia, Department of Geriatric Medicine, Dokuz Eylul University, School of Medicine, Balcova, Izmir 35340, Turkey
- Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Topkapı, Turgut Özal Millet Cd, Istanbul 34093, Turkey
- Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, 106, Valencia 46026, Spain
- Oxford Parkinson's Disease Centre, University of Oxford, Oxford, UK
- Dementia Research Centre, University College London, 8–11 Queen Square, London WC1N 3AR, UK
- Division of Psychiatry, University College London, 6th Floor, Wings A and B, Maple House, 149 Tottenham Ct Rd, London W1T 7NF, UK
- Essex Partnership University NHS Foundation Trust, Sankey House, 81 High Rd, Pitsea, Basildon SS13 3BB, UK
- Centre for Healthy Brain Ageing, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, 16 De Crespigny Park, London SE5 8AB, UK
- The Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, White City Campus, 90 Wood Lane, London W12 0BZ, UK
- Facultad de Ciencias de La Salud, Universidad Fernando Pessoa Canarias, Calle Alcalde Francisco Hernández González, 28, Las Palmas 35001, Spain
- School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Australia
- National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK
- School of Health Sciences, Faculty of Medicine and Health, University of Sydney, Australia
- Functional Imaging Laboratory, Department of Imaging Neuroscience, Institute of Neurology, University College London, 12 Queen Square, London WC1N 3AR, UK
- Department of Neurology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia
Abstract
Background: Lewy body diseases (LBD) collectively share α-synuclein Lewy pathology, yet present wide clinical heterogeneity, with overlapping motor and non-motor features and progression patterns that challenge traditional diagnostic boundaries.
Methods: To resolve this spatiotemporal heterogeneity at the biological level, we applied a data-driven atrophy progression framework to MRI data from 833 individuals across Parkinson’s disease, dementia with Lewy bodies, and prodromal isolated REM sleep behaviour disorder using the Subtype and Stage Inference algorithm.
Findings: Four transdiagnostic subtypes (A: Early cortico-limbic/
Interpretation: These biologically relevant spatiotemporal atrophy subtypes provide an interpretable stratification of patients with LBD, with the potential to refine prognosis, improve clinical trial stratification, and guide precision therapeutic approaches.
Funding: This work was made possible by an Ignition grant from the 10.13039/
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
No file of the authors' code could be read here: it is described below, and read at its source.
ucl-usyd-transcend.github.io
Availability: 1 check, the latest on 27 September 2026: the link answers (HTTP 200)
- 27 September 2026: the link answers (HTTP 200)
The paper's code and data availability statement is in the Data section.
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Data
No dataset and no data link were found in the paper.
Data sharing statement
Data supporting the findings of this study are available from the corresponding authors, upon reasonable request. The pySuStaIn algorithm can be publicly accessed at https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 3, 28 September 2026
- Authors: added Gonzalo Castro Leal (0000-0002-5496-971X); Ahmet Turan Isik (0000-0001-5867-6503); Eric Westman (0000-0002-3115-2977); Neil P. Oxtoby (0000-0003-0203-3909); removed Gonzalo Castro Leal; Ahmet Turan Isik; Eric Westman; Neil P. Oxtoby
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, pages, dates, 30 authors, 6 keywords, 11 MeSH terms, 110 funders, 79 references, 1 RRID.
Cite
This paper
Konuri, A., Leal, G. C., Zebarjadi, N., Habich, A., Castellanos-Perilla, N., Gonzalez, M. C., Taylor, J.-P., Firbank, M., Alcolea, D., Bejanin, A., Segers, K., Benoit, F., Isik, A. T., Samanci, B., Cháfer-Pericás, C., Wade-Martins, R., Hu, M. T., Bhome, R., Dobreva, I., . . . Matar, E. (2026). Data-driven trajectories of atrophy explain clinical heterogeneity across Lewy body diseases. EBioMedicine, 131, 106400. https://
BibTeX
@article{konuri2026data,
author = {Konuri, Ajay and Leal, Gonzalo Castro and Zebarjadi, Niloufar and Habich, Annegret and Castellanos-Perilla, Nicolás and Gonzalez, María Camila and Taylor, John-Paul and Firbank, Michael and Alcolea, Daniel and Bejanin, Alexandre and Segers, Kurt and Benoit, Florence and Isik, Ahmet Turan and Samanci, Bedia and Cháfer-Pericás, Consuelo and Wade-Martins, Richard and Hu, Michele T.M. and Bhome, Rohan and Dobreva, Ivelina and Walker, Zuzana and Aarsland, Dag and Westman, Eric and Ferreira, Daniel and Halliday, Glenda and Lewis, Simon J.G. and Weil, Rimona S. and Landin-Romero, Ramon and Lambert, Christian and Oxtoby, Neil P. and Matar, Elie},
title = {{Data-driven trajectories of atrophy explain clinical heterogeneity across Lewy body diseases}},
journal = {EBioMedicine},
year = {2026},
month = aug,
volume = {131},
pages = {106400},
publisher = {Elsevier},
issn = {2352-3964},
doi = {10.1016/
url = {https://
pmid = {42556137},
pmcid = {PMC13471053}
}
RIS
TY - JOUR
AU - Konuri, Ajay
AU - Leal, Gonzalo Castro
AU - Zebarjadi, Niloufar
AU - Habich, Annegret
AU - Castellanos-Perilla, Nicolás
AU - Gonzalez, María Camila
AU - Taylor, John-Paul
AU - Firbank, Michael
AU - Alcolea, Daniel
AU - Bejanin, Alexandre
AU - Segers, Kurt
AU - Benoit, Florence
AU - Isik, Ahmet Turan
AU - Samanci, Bedia
AU - Cháfer-Pericás, Consuelo
AU - Wade-Martins, Richard
AU - Hu, Michele T.M.
AU - Bhome, Rohan
AU - Dobreva, Ivelina
AU - Walker, Zuzana
AU - Aarsland, Dag
AU - Westman, Eric
AU - Ferreira, Daniel
AU - Halliday, Glenda
AU - Lewis, Simon J.G.
AU - Weil, Rimona S.
AU - Landin-Romero, Ramon
AU - Lambert, Christian
AU - Oxtoby, Neil P.
AU - Matar, Elie
TI - Data-driven trajectories of atrophy explain clinical heterogeneity across Lewy body diseases
T2 - EBioMedicine
J2 - eBioMedicine
PY - 2026
DA - 2026/
VL - 131
SP - 106400
SN - 2352-3964
PB - Elsevier
DO - 10.1016/
UR - https://
LA - en
ER -
CSL-JSON
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