Evidence map›Paper›PMID 41085135›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Cortical thickness subtypes in cognitively unimpaired individuals: Differential network and transcriptomic vulnerability to cortical thinning.

Luigi Lorenzini, Mario Tranfa, Leonard Pieperhoff, Federico Masserini, Mara Ten Kate, Lyduine E Collij, Giuseppe Pontillo, Emma S Luckett, Alle Meije Wink, Henk Jmm Mutsaerts and 28 more

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Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

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5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

38 authors.

Luigi LorenziniDepartment of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, Vrije Universiteit, Amsterdam, The Netherlands.ORCID 0000-0002-9756-881X
Mario TranfaDepartment of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, Vrije Universiteit, Amsterdam, The Netherlands.
Leonard PieperhoffDepartment of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, Vrije Universiteit, Amsterdam, The Netherlands.
Federico MasseriniDepartment of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, Vrije Universiteit, Amsterdam, The Netherlands.
Mara Ten KateDepartment of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, Vrije Universiteit, Amsterdam, The Netherlands.
Lyduine E CollijDepartment of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, Vrije Universiteit, Amsterdam, The Netherlands.
Giuseppe PontilloDepartment of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, Vrije Universiteit, Amsterdam, The Netherlands.
Emma S LuckettDepartment of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, Vrije Universiteit, Amsterdam, The Netherlands.
Alle Meije WinkDepartment of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, Vrije Universiteit, Amsterdam, The Netherlands.
Henk Jmm MutsaertsDepartment of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, Vrije Universiteit, Amsterdam, The Netherlands.
Tiago Gil OliveiraLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
Daniele AltomareCompetence Centre on Ageing (CCA); Department of Business Economics Health and Social Care (DEASS);, University of Applied Sciences and Arts of Southern Switzerland (SUPSI), Manno, Switzerland.
Mercè BoadaAce Alzheimer Center, Barcelona-Universitat Internacional de Catalunya, Barcelona, Spain.
Anouk den BraberAlzheimer Center Amsterdam, Department of Neurology, Amsterdam UMC, Amsterdam, The Netherlands.
Cindy BirckAlzheimer Europe, Alzheimer Europe, Bertrange, Luxembourg.
Christopher BuckleyGE HealthCare, GE HealthCare, Amersham, UK.
Gill FarrarGE HealthCare, GE HealthCare, Amersham, UK.
Wiesje van der FlierAlzheimer Center Amsterdam, Department of Neurology, Amsterdam UMC, Amsterdam, The Netherlands.
Giovanni B FrisoniDepartment of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland.
Rossella GismondiLife Molecular Imaging, Life Molecular Imaging, Berlin, Germania.
Juan Domingo GispertBarcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain.
Bernard J HanseeuwDepartment of Neurology, Cliniques Universitaires Saint-Luc, Bruxelles, Belgio.
Frank JessenDepartment of Psychiatry and Psychotherapy, University Hospital Cologne, Cologne, Germany.
Marta MarquiéAce Alzheimer Center, Barcelona-Universitat Internacional de Catalunya, Barcelona, Spain.
Anja MettGE HealthCare, GE HealthCare, Amersham, UK.
Craig RitchieScottish Brain Sciences, Scottish Brain Sciences, Edinburgh, Scotland.
Gemma SalvadóClinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.
Michael SchöllDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Mahnaz ShekariBarcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain.
Andrew W StephensLife Molecular Imaging, Life Molecular Imaging, Berlin, Germania.
Betty M TijmsAlzheimer Center Amsterdam, Department of Neurology, Amsterdam UMC, Amsterdam, The Netherlands.
David Vállez GarcíaBarcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain.
Rik VandenbergheLeuven Brain Institute, KU Leuven, Leuven, Belgium.
Pieter Jelle VisserAlzheimer Center Amsterdam, Department of Neurology, Amsterdam UMC, Amsterdam, The Netherlands.
Luca RoccatagliataDepartment of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.
Neil P OxtobyUCL Hawkes Institute and Department of Computer Science, University College London, London, UK.
Matteo PardiniDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy.
Frederik BarkhofDepartment of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, Vrije Universiteit, Amsterdam, The Netherlands.

Funding

Acción Estratégica en Salud, integrated in the Spanish National RCDCI PlanADAPTED 115975Alzheimerfonden AF-1012218Alzheimerfonden AF-980942Alzheimerfonden AF-994514Alzheimer Nederland WE.03-2021-16Alzheimer's Association 23AARF-102966Alzheimer's Association Grant SG-21-818099-EPADAlzheimer's Association Research Fellowship AARF-22-972612Alzheimer's Disease Data InitiativeAlzheimer's Disease Data Initiative (ADDI)Brightfocus Foundation A2024007FBrightFocus Foundation A2024007FCIBERNEDDutch Heart Foundation 03-004-2020-T049Early Detection of Alzheimer's Disease Subtypes E-DADSEarly Detection of Alzheimer's Disease Subtypes EU JPND MR/T046422/1Early Detection of Alzheimer's Disease Subtypes project E-DADSEarly Detection of Alzheimer's Disease Subtypes project EU JPND MR/T046422/1EU/EFPIA Innovative Medicines Initiative Joint UndertakingEU/EFPIA Innovative Medicines Initiative Joint Undertaking EPAD 115736EU Euronanomed3 Program JCT2017 AC17/00100EU Euronanomed3 Program JCT2017 MOPEADEU Joint Program for Neurodegenerative Disease ResearchEU Joint Programme - Neurodegenerative Disease Research DEBBIE JPND2020-568-106European Union Horizon 2020 research and innovation programme ASPIRE E!113701European Union's Horizon 2020 Research and Innovation Program 101061836European Union's Horizon 2020 Research and Innovation Programme 796706GECONEU 2023-1-ELO1-KAZZ0-HED-000032173Greta och Johan KocksH2020 Marie Skłodowska-Curie Actions 101108819Hartstichting 03-004-2020-T049he Fondo Europeo de Desarrollo Regional (FEDER - "Una manera de Hacer Europa"); Fundació "La Caixa" and Grífols (GR@ACE project)Innovative Medicine Initiative 115985Innovative Medicine Initiative (IMI)Innovative Medicines Initiative 115736Innovative Medicines Initiative (IMI) 2 Joint Undertaking 115952Instituto de Salud Carlos III (ISCIII)- Subdirección General de EvaluaciónISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER-Una manera de hacer Europa) PI19/00335Joint Program for Neurodegenerative Diseases AC19/00097National Institute for Health Research University College London Hospitals Biomedical Research CentreNetherlands Organisation for health Research and Development and Alzheimer Nederland DEBBIE JPND2020-568-106PMP-DEGESCO PMP22/00022PREADAPTPreDADQoL, ERA-NET (call 2015) AC15/00082Proyectos de Investigación de Medicina Personalizada (ISCIII)Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's Disease) at Lund UniversityTARTAGLIA
6 · The paper itself

Abstract

introductionThe emergence, stability, and contributing factors of Alzheimer's disease (AD) gray matter subtypes remain unclear.

methodsWe analyzed data from 1323 individuals without a diagnosis of dementia (CDR < 1) with T1w-MRI and amyloid-PET, including 622 with longitudinal data (3.66 ± 1.78 years). Cortical thickness subtypes were identified using a non-negative matrix factorization (NMF) clustering algorithm. We examined clinical and demographic differences, subtype stability, and longitudinal thinning patterns using brain network models and imaging-transcriptomic analysis. Replication was performed with an alternative clustering approach and a validation cohort.

resultsTwo stable subtypes emerged: limbic-predominant and hippocampal-sparing. Limbic-predominant participants were older, had higher amyloid burden, and faster memory decline, while hippocampal-sparing individuals showed greater attention and executive function decline. Distinct thinning patterns were linked to specific network properties and gene expression profiles. DISCUSSION: These MRI-based subtypes reflect underlying pathophysiological mechanisms and may aid in prognostication and clinical trial stratification. HIGHLIGHTS: Two gray matter thickness subtypes can already be identified in preclinical stages, exhibiting distinct clinical characteristics and progression patterns. Individual subtype assignment remains stable over time. Longitudinal cortical thinning patterns follow distinct network- and transcriptomic-based mechanisms within each subtype.

Indexed as

Brain Cortical ThicknessCerebral CortexCerebral Cortical ThinningGray MatterTranscriptomeAgedAged, 80 and overAlzheimer DiseaseFemaleHippocampusHumansLongitudinal StudiesMagnetic Resonance ImagingMaleMiddle AgedPositron-Emission Tomographybiological pathwaysmagnetic resonance imagingpolygenic riskpreclinical Alzheimer's

Identifiers

PMID41085135
PMCPMC12519513

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