Cortical gray-white matter contrast alterations precede amyloid-β positivity and macrostructural changes in older adults without dementia.
Overview
and 15 other authors
Matteo Pardini3,26, Luca Roccataglia27,28, Andrew W. Stephens29, Chris Buckley9, Gill Farrar9, Frank Jessen30, Juan Domingo Gispert31, Gemma Salvadó31,32, Emma S. Luckett1,2,17,33, Henk‐Jan MM Mutsaerts1,2, Alle Meije Wink1,2, Lyduine E. Collij1,2, Frederik Barkhof1,2, Tiago Gil Oliveira4,5,34, the AMYPAD consortium34 affiliations
- Department of Radiology and Nuclear Medicine Vrije Universiteit Amsterdam, Amsterdam University Medical Center Amsterdam the Netherlands
- Brain imaging Amsterdam Neuroscience Amsterdam the Netherlands
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI) University of Genoa Genoa Italy
- Life and Health Sciences Research Institute (ICVS) School of Medicine, University of Minho Braga Portugal
- Department of Neuroradiology Hospital de Braga, ULS Braga Braga Portugal
- Department of Anatomy and Neurosciences Amsterdam UMC location VUmc Amsterdam the Netherlands
- Neurodegeneration Amsterdam Neuroscience Amsterdam the Netherlands
- Department of Advanced Biomedical Sciences University of Naples “Federico II” Naples Italy
- GE HealthCare Amersham UK
- Department of Medical Physics and Biomedical Engineering UCL London UK
- “L. Sacco” Department of Biomedical and Clinical Sciences University of Milan Milan Italy
- IXICO plc London London UK
- Scottish Brain Sciences Edinburgh UK
- Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya Barcelona Spain
- Networking Research Center on Neurodegenerative Diseases (CIBERNED) Instituto de Salud Carlos III Madrid Spain
- Alzheimer Center Amsterdam, Neurology, Amsterdam UMC Amsterdam the Netherlands
- Laboratory for Cognitive Neurology KU Leuven Leuven Belgium
- Department of Neurology Cliniques Universitaires Saint‐Luc Brussels Belgium
- Institute of Neuroscience Université catholique de Louvain Brussels Belgium
- Center for Research and Advanced Therapies. CITA Alzheimer Foundation Donostia‐San Sebastián Spain
- ToNIC Toulouse NeuroImaging Center, Université Toulouse 3, Inserm Toulouse France
- Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg Gothenburg Sweden
- Wallenberg Centre for Molecular and Translational Medicine University of Gothenburg Gothenburg Sweden
- Dementia Research Centre, Institute of Neurology University College London London UK
- Hôpitaux Universitaires de Genève Geneva Switzerland
- IRCCS Ospedale Policlinico San Martino Genoa Italy
- Department of Health Sciences (DISSAL) University of Genoa Genoa Italy
- Department of Neuroradiology IRCCS Ospedale Policlinico San Martino Genoa Italy
- Life Molecular Imaging GmbH Berlin Germany
- Department of Psychiatry and Psychotherapy University Hospital Cologne Cologne Germany
- Barcelonaβeta Brain Research Center Pasqual Maragall Foundation Barcelona Spain
- Clinical Memory Research Unit Department of Clinical Sciences in Malmö Lund University Lund Sweden
- Laboratory for Complex Genetics KU Leuven Leuven Belgium
- ICVS/3B's ‐ PT Government Associate Laboratory University of Minho Braga Portugal
Abstract
INTRODUCTION: Early Alzheimer's disease (AD) involves subtle cortical changes that may precede atrophy. Magnetic resonance imaging (MRI) microstructural markers may detect earlier pathology than classical morphometry.
METHODS: We analyzed cross‐sectional MRI and amyloid‐β (Aβ) positron emission tomography (PET) data from 1323 non‐demented AMYPAD participants. Cortical volume, thickness, gray–white matter contrast (GWC), and mean diffusivity (MD) were related to global Aβ burden and estimated time to Aβ‐positivity using regression, correlation, and change‐point analyses.
RESULTS: Microstructural measures showed stronger age associations than macrostructural measures, whereas all measures were unaffected by apolipoprotein E (APOE) ‐ε4 carriership. GWC and MD showed minimal overlap with volume and thickness. Higher Aβ burden was most strongly associated with reduced GWC and cortical thinning. Change‐point analyses showed GWC alterations preceded Aβ‐positivity by several years.
DISCUSSION: Cortical microstructural MRI, particularly GWC, changes earlier than atrophy and may serve as an early in vivo marker of AD pathology.
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
Code
The paper links to its data, not to its authors' code: see the Data section.
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Data
Datasets cited
- zenodo:7962924 — at Zenodo; found in “Data availability”
- zenodo:8017084 — at Zenodo; found in the references
Data availability
Data for this study were drawn from the AMYPAD PNHS v202306, available on the AD Workbench and can be requested via the AD Workbench FAIR portal under https://
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
Versions
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 35 authors, 6 keywords, 13 MeSH terms, 5 funders, 80 references.
Cite
This paper
Pieperhoff, L., Lorenzini, L., Almeida, F., Tranfa, M., Bollack, A., Arunachalam, P., Masserini, F., Wolz, R., Grootoonk, S., Ritchie, C., Boada, M., Marquié, M., Vijverberg, J., Vandenberghe, R., Hanseeuw, B. J., Martinez‐Lage, P., Payoux, P., Visser, P. J., Schöll, M., . . . the AMYPAD consortium. (2026). Cortical gray-white matter contrast alterations precede amyloid-β positivity and macrostructural changes in older adults without dementia. Alzheimer's & dementia : the journal of the Alzheimer's Association, 22(6), e71609. https://
BibTeX
@article{pieperhoff2026c
author = {Pieperhoff, Leonard and Lorenzini, Luigi and Almeida, Francisco and Tranfa, Mario and Bollack, Ariane and Arunachalam, Prithvi and Masserini, Federico and Wolz, Robin and Grootoonk, Sylke and Ritchie, Craig and Boada, Mercè and Marquié, Marta and Vijverberg, Jort and Vandenberghe, Rik and Hanseeuw, Bernard J. and Martinez‐Lage, Pablo and Payoux, Pierre and Visser, Pieter Jelle and Schöll, Michael and Frisoni, Giovanni B. and Pardini, Matteo and Roccataglia, Luca and Stephens, Andrew W. and Buckley, Chris and Farrar, Gill and Jessen, Frank and Gispert, Juan Domingo and Salvadó, Gemma and Luckett, Emma S. and Mutsaerts, Henk‐Jan MM and Wink, Alle Meije and Collij, Lyduine E. and Barkhof, Frederik and Oliveira, Tiago Gil and {the AMYPAD consortium}},
title = {{Cortical gray-white matter contrast alterations precede amyloid-β positivity and macrostructural changes in older adults without dementia}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2026},
month = jun,
volume = {22},
number = {6},
pages = {e71609},
publisher = {Wiley},
issn = {1552-5260},
doi = {10.1002/
url = {https://
pmid = {42337956},
pmcid = {PMC13290647}
}
RIS
TY - JOUR
AU - Pieperhoff, Leonard
AU - Lorenzini, Luigi
AU - Almeida, Francisco
AU - Tranfa, Mario
AU - Bollack, Ariane
AU - Arunachalam, Prithvi
AU - Masserini, Federico
AU - Wolz, Robin
AU - Grootoonk, Sylke
AU - Ritchie, Craig
AU - Boada, Mercè
AU - Marquié, Marta
AU - Vijverberg, Jort
AU - Vandenberghe, Rik
AU - Hanseeuw, Bernard J.
AU - Martinez‐Lage, Pablo
AU - Payoux, Pierre
AU - Visser, Pieter Jelle
AU - Schöll, Michael
AU - Frisoni, Giovanni B.
AU - Pardini, Matteo
AU - Roccataglia, Luca
AU - Stephens, Andrew W.
AU - Buckley, Chris
AU - Farrar, Gill
AU - Jessen, Frank
AU - Gispert, Juan Domingo
AU - Salvadó, Gemma
AU - Luckett, Emma S.
AU - Mutsaerts, Henk‐Jan MM
AU - Wink, Alle Meije
AU - Collij, Lyduine E.
AU - Barkhof, Frederik
AU - Oliveira, Tiago Gil
AU - the AMYPAD consortium
TI - Cortical gray-white matter contrast alterations precede amyloid-β positivity and macrostructural changes in older adults without dementia
T2 - Alzheimer's & dementia : the journal of the Alzheimer's Association
J2 - Alzheimers Dement
PY - 2026
DA - 2026/
VL - 22
IS - 6
SP - e71609
SN - 1552-5260
PB - Wiley
DO - 10.1002/
UR - https://
LA - en
ER -
CSL-JSON
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