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EBioMedicine2026;131106400.August 5, 2026Journal Article

Data-driven trajectories of atrophy explain clinical heterogeneity across Lewy body diseases.

Ajay Konuri1, Gonzalo Castro Leal2, Niloufar Zebarjadi3, Annegret Habich3, Nicolás Castellanos-Perilla4, María Camila Gonzalez5, John-Paul Taylor6, Michael Firbank6, Daniel Alcolea7, Alexandre Bejanin7, Kurt Segers8, Florence Benoit8, Ahmet Turan Isik9, Bedia Samanci10, Consuelo Cháfer-Pericás11, Richard Wade-Martins12, Michele T M Hu12, Rohan Bhome13, Ivelina Dobreva14, Zuzana Walker15, Dag Aarsland16, Eric Westman17, Daniel Ferreira18, Glenda Halliday19, Simon J G Lewis20, Rimona S Weil21, Ramon Landin-Romero22, Christian Lambert23, Neil P Oxtoby24, Elie Matar25
1Central 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.
2UCL 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.
3Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Center for Alzheimer Research, Karolinska Institutet, Blickagången 16, Huddinge, Stockholm 141 52, Sweden.
4Division 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.
5Centre for Age-Related Medicine (SESAM), Stavanger University Hospital, Postboks 8100, Stavanger 4068, Norway.
6Translational and Clinical Research Institute, Campus for Ageing and Vitality, Newcastle Upon Tyne NE4 5PL, UK.
7Sant 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.
8Neurology and Geriatrics Department, Brugmann University Hospital, Université Libre De Bruxelles, Place Arthur Van Gehuchten 4, Brussels 1020, Belgium.
9Unit for Brain Aging and Dementia, Department of Geriatric Medicine, Dokuz Eylul University, School of Medicine, Balcova, Izmir 35340, Turkey.
10Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Topkapı, Turgut Özal Millet Cd, Istanbul 34093, Turkey.
11Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, 106, Valencia 46026, Spain.
12Oxford Parkinson's Disease Centre, University of Oxford, Oxford, UK.
13UCL Hawkes Institute, University College London, 90 High Holborn, London WC1V 6LJ, UK; Dementia Research Centre, University College London, 8-11 Queen Square, London WC1N 3AR, UK.
14Dementia Research Centre, University College London, 8-11 Queen Square, London WC1N 3AR, UK.
15Division 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.
16Translational and Clinical Research Institute, Campus for Ageing and Vitality, Newcastle Upon Tyne NE4 5PL, UK; Centre for Healthy Brain Ageing, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, 16 De Crespigny Park, London SE5 8AB, UK.
17Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Center for Alzheimer Research, Karolinska Institutet, Blickagången 16, Huddinge, Stockholm 141 52, Sweden; The Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, White City Campus, 90 Wood Lane, London W12 0BZ, UK.
18Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Center for Alzheimer Research, Karolinska Institutet, Blickagången 16, Huddinge, Stockholm 141 52, Sweden; Facultad de Ciencias de La Salud, Universidad Fernando Pessoa Canarias, Calle Alcalde Francisco Hernández González, 28, Las Palmas 35001, Spain.
19Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Australia; School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Australia.
20Parkinson's Disease Research Centre, Macquarie Medical School, Macquarie University, Australia.
21Division of Psychiatry, University College London, 6th Floor, Wings A and B, Maple House, 149 Tottenham Ct Rd, London W1T 7NF, UK; National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK.
22Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Australia; School of Health Sciences, Faculty of Medicine and Health, University of Sydney, Australia.
23Functional Imaging Laboratory, Department of Imaging Neuroscience, Institute of Neurology, University College London, 12 Queen Square, London WC1N 3AR, UK.
24UCL 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. Electronic address: n.oxtoby@ucl.ac.uk.
25Central Clinical School, Faculty of Medicine and Health, University of Sydney, Australia; Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Australia; Department of Neurology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia. Electronic address: elie.matar@sydney.edu.au.
PubMed DOI

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 83…

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