Evidence map›Paper›PMID 42556137›Full record

ArticleEBioMedicine2026

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

Ajay Konuri, Gonzalo Castro Leal, Niloufar Zebarjadi, Annegret Habich, Nicolás Castellanos-Perilla, María Camila Gonzalez, John-Paul Taylor, Michael Firbank, Daniel Alcolea, Alexandre Bejanin and 20 more

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Article in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

30 authors.

Ajay KonuriCentral 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.
Gonzalo Castro LealUCL 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.
Niloufar ZebarjadiDivision of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Center for Alzheimer Research, Karolinska Institutet, Blickagången 16, Huddinge, Stockholm 141 52, Sweden.
Annegret HabichDivision of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Center for Alzheimer Research, Karolinska Institutet, Blickagången 16, Huddinge, Stockholm 141 52, Sweden.
Nicolás Castellanos-PerillaDivision 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.
María Camila GonzalezCentre for Age-Related Medicine (SESAM), Stavanger University Hospital, Postboks 8100, Stavanger 4068, Norway.
John-Paul TaylorTranslational and Clinical Research Institute, Campus for Ageing and Vitality, Newcastle Upon Tyne NE4 5PL, UK.
Michael FirbankTranslational and Clinical Research Institute, Campus for Ageing and Vitality, Newcastle Upon Tyne NE4 5PL, UK.
Daniel AlcoleaSant 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.
Alexandre BejaninSant 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.
Kurt SegersNeurology and Geriatrics Department, Brugmann University Hospital, Université Libre De Bruxelles, Place Arthur Van Gehuchten 4, Brussels 1020, Belgium.
Florence BenoitNeurology and Geriatrics Department, Brugmann University Hospital, Université Libre De Bruxelles, Place Arthur Van Gehuchten 4, Brussels 1020, Belgium.
Ahmet Turan IsikUnit for Brain Aging and Dementia, Department of Geriatric Medicine, Dokuz Eylul University, School of Medicine, Balcova, Izmir 35340, Turkey.
Bedia SamanciBehavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Topkapı, Turgut Özal Millet Cd, Istanbul 34093, Turkey.
Consuelo Cháfer-PericásInstituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, 106, Valencia 46026, Spain.
Richard Wade-MartinsOxford Parkinson's Disease Centre, University of Oxford, Oxford, UK.
Michele T M HuOxford Parkinson's Disease Centre, University of Oxford, Oxford, UK.
Rohan BhomeUCL 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.
Ivelina DobrevaDementia Research Centre, University College London, 8-11 Queen Square, London WC1N 3AR, UK.
Zuzana WalkerDivision 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.
Dag AarslandTranslational 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.
Eric WestmanDivision 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.
Daniel FerreiraDivision 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.
Glenda HallidayBrain 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.
Simon J G LewisParkinson's Disease Research Centre, Macquarie Medical School, Macquarie University, Australia.
Rimona S WeilDivision 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.
Ramon Landin-RomeroBrain 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.
Christian LambertFunctional Imaging Laboratory, Department of Imaging Neuroscience, Institute of Neurology, University College London, 12 Queen Square, London WC1N 3AR, UK.
Neil P OxtobyUCL 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.
Elie MatarCentral 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.

Funding

Technology and Remote Assessment CoreU19AG063911 · NIA · MAYO CLINIC ROCHESTER · PI ADAM L. BOXER · 2019 to 2026
$120.9M
WU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8M
Early Onset AD Consortium - the LEAD Study (LEADS)U01AG057195 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI APOSTOLOVA, LIANA G, CARRILLO, MARIA C · 2018 to 2023
$70.3M
Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5M
The Clinical Significance of Incidental White Matter Lesions on MRI Amongst a Diverse Population with Cognitive Complaints (INDEED)U19NS120384 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Kumar B. Rajan · 2020 to 2026
$61.9M
THERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI GRABOWSKI, THOMAS J. · 1985 to 2019
$57.2M
The natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 2005 to 2025
$49.5M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
Satellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3M
National Alzheimer's Coordinating CenterU24AG072122 · NIA · UNIVERSITY OF WASHINGTON · PI STEPHENS, KARI A · 2021 to 2025
$45.8M
TREATMENT OF DEPRESSION IN ALZHEIMER'S DISEASEP50AG005133 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SWEET, ROBERT A · 1985 to 2019
$43.0M
Washington University Institute of Clinical and Translational SciencesUL1TR000448 · NCATS · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2012 to 2016
$41.4M
NCATS NIH HHS UL1 TR000448NCATS NIH HHS UL1 TR002345NCRR NIH HHS U24 RR021382NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P20 AG068053NIA NIH HHS P20 AG068077NIA NIH HHS P20 AG068082NIA NIH HHS P30 AG010129NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG013846NIA NIH HHS P30 AG013854NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG035982NIA NIH HHS P30 AG053760NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062428NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG062677NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066468NIA NIH HHS P30 AG066506NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066508NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG066511NIA NIH HHS P30 AG066512NIA NIH HHS P30 AG066514NIA NIH HHS P30 AG066515NIA NIH HHS P30 AG066518NIA NIH HHS P30 AG066519NIA NIH HHS P30 AG066530NIA NIH HHS P30 AG066546NIA NIH HHS P30 AG072931NIA NIH HHS P30 AG072946NIA NIH HHS P30 AG072947NIA NIH HHS P30 AG072958NIA NIH HHS P30 AG072959NIA NIH HHS P30 AG072972NIA NIH HHS P30 AG072973NIA NIH HHS P30 AG072975NIA NIH HHS P30 AG072976NIA NIH HHS P30 AG072977NIA NIH HHS P30 AG072978NIA NIH HHS P30 AG072979NIA NIH HHS P30 AG072980NIA NIH HHS P30 AG086401NIA NIH HHS P30 AG086403NIA NIH HHS P30 AG086404NIA NIH HHS P30 AG092752NIA NIH HHS P50 AG005133NIA NIH HHS P50 AG005136NIA NIH HHS P50 AG005142NIA NIH HHS P50 AG008702NIA NIH HHS P50 AG016573NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG033514NIA NIH HHS P50 AG047266NIA NIH HHS P50 AG047270NIA NIH HHS P50 AG047366NIA NIH HHS R01 AG019771NIA NIH HHS R01 AG021910NIA NIH HHS R01 AG043434NIA NIH HHS R01 AG045571NIA NIH HHS R01 AG052560NIA NIH HHS R01 AG053509NIA NIH HHS R01 AG053993NIA NIH HHS R01 AG054110NIA NIH HHS R01 AG055005NIA NIH HHS R01 AG056031NIA NIH HHS R01 AG056258NIA NIH HHS R01 AG056531NIA NIH HHS R01 AG058724NIA NIH HHS R01 AG061788NIA NIH HHS R01 AG062276NIA NIH HHS R01 AG067781NIA NIH HHS R01 AG068338NIA NIH HHS R01 AG069453NIA NIH HHS R01 AG073235NIA NIH HHS R01 AG077444NIA NIH HHS R01 AG079280NIA NIH HHS R35 AG072262NIA NIH HHS R56 AG045571NIA NIH HHS R56 AG074321NIA NIH HHS U01 AG057195NIA NIH HHS U19 AG063911NIA NIH HHS U19 AG073153NIA NIH HHS U24 AG067418NIA NIH HHS U24 AG072122NIBIB NIH HHS R01 EB009352NIDCD NIH HHS R01 DC008552NIH HHS S10 OD026738NIMH NIH HHS P50 MH071616NINDS NIH HHS P30 NS098577NINDS NIH HHS R01 NS075075NINDS NIH HHS U19 NS120384RRD VA I01 RX001534RRD VA I21 RX001381Wellcome Trust
6 · The paper itself

Abstract

backgroundLewy 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.

methodsTo 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.

findingsFour transdiagnostic subtypes (A: Early cortico-limbic/late basal ganglia, B: Early basal ganglia/late limbic, C: Early temporo-limbic/late basal ganglia, and D: Early basal ganglia-cingulate/late cortex) emerged, each defined by a distinct spatiotemporal progression of atrophy that explained cognitive, motor, and psychiatric variability. An early cortico-limbic/late basal ganglia subtype represented a dementia-prone subtype across clinical diagnoses, with limbic involvement associating with the emergence of visual hallucinations.

interpretationThese 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.

fundingThis work was made possible by an Ignition grant from the University of Sydney and University College London (Global Engagement Fund).

Indexed as

Lewy Body DiseaseAgedAtrophyBrainDisease ProgressionFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedParkinson DiseaseDementiaHeterogeneityLewy body diseasesMachine learningNeurodegenerationSubtypes

Identifiers

PMID42556137
PMCPMC13471053

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.