Cortical gray–white matter contrast alterations precede amyloid‐β positivity and macrostructural changes in older adults without dementia
Leonard Pieperhoff, Luigi Lorenzini, Francisco Almeida, Mario Tranfa, Ariane Bollack, Prithvi Arunachalam, Federico Masserini, Robin Wolz, Sylke Grootoonk, Craig Ritchie, Mercè Boada, Marta Marquié, Jort Vijverberg, Rik Vandenberghe, Bernard J. Hanseeuw, Pablo Martinez‐Lage, Pierre Payoux, Pieter Jelle Visser, Michael Schöll, Giovanni B. Frisoni, Matteo Pardini, Luca Roccataglia, Andrew W. Stephens, Chris Buckley, Gill Farrar, Frank Jessen, Juan Domingo Gispert, Gemma Salvadó, Emma S. Luckett, Henk‐Jan MM Mutsaerts, Alle Meije Wink, Lyduine E. Collij, Frederik Barkhof, Tiago Gil Oliveira,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.