TY - JOUR
T1 - Grey-Matter Structure Markers of Alzheimer's Disease, Alzheimer's Conversion, Functioning and Cognition
T2 - A Meta-Analysis Across 11 Cohorts
AU - Couvy-Duchesne, Baptiste
AU - Frouin, Vincent
AU - Bouteloup, Vincent
AU - Koussis, Nikitas
AU - Sidorenko, Julia
AU - Jiang, Jiyang
AU - Wink, Alle Meije
AU - Lorenzini, Luigi
AU - Barkhof, Frederik
AU - Trollor, Julian N.
AU - Mangin, Jean-François
AU - Sachdev, Perminder S.
AU - Brodaty, Henry
AU - Alzheimer’s Disease Neuroimaging Initiative
AU - the Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing
AU - Lupton, Michelle K.
AU - Breakspear, Michael
AU - Colliot, Olivier
AU - the Alzheimer's Disease Repository Without Borders Investigators
AU - Visscher, Peter M.
AU - the MEMENTO cohort Study Group
AU - Wray, Naomi R.
N1 - Publisher Copyright:
© 2025 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.
PY - 2025/2/1
Y1 - 2025/2/1
N2 - Alzheimer's disease (AD) brain markers are needed to select people with early-stage AD for clinical trials and as quantitative endpoint measures in trials. Using 10 clinical cohorts (N = 9140) and the community volunteer UK Biobank (N = 37,664) we performed region of interest (ROI) and vertex-wise analyses of grey-matter structure (thickness, surface area and volume). We identified 94 trait-ROI significant associations, and 307 distinct cluster of vertex-associations, which partly overlap the ROI associations. For AD versus controls, smaller hippocampus, amygdala and of the medial temporal lobe (fusiform and parahippocampal gyri) was confirmed and the vertex-wise results provided unprecedented localisation of some of the associated region. We replicated AD associated differences in several subcortical (putamen, accumbens) and cortical regions (inferior parietal, postcentral, middle temporal, transverse temporal, inferior temporal, paracentral, superior frontal). These grey-matter regions and their relative effect sizes can help refine our understanding of the brain regions that may drive or precede the widespread brain atrophy observed in AD. An AD grey-matter score evaluated in independent cohorts was significantly associated with cognition, MCI status, AD conversion (progression from cognitively normal or MCI to AD), genetic risk, and tau concentration in individuals with none or mild cognitive impairments (AUC in 0.54–0.70, p-value < 5e-4). In addition, some of the grey-matter regions associated with cognitive impairment, progression to AD (‘conversion’), and cognition/functional scores were also associated with AD, which sheds light on the grey-matter markers of disease stages, and their relationship with cognitive or functional impairment. Our multi-cohort approach provides robust and fine-grained maps the grey-matter structures associated with AD, symptoms, and progression, and calls for even larger initiatives to unveil the full complexity of grey-matter structure in AD.
AB - Alzheimer's disease (AD) brain markers are needed to select people with early-stage AD for clinical trials and as quantitative endpoint measures in trials. Using 10 clinical cohorts (N = 9140) and the community volunteer UK Biobank (N = 37,664) we performed region of interest (ROI) and vertex-wise analyses of grey-matter structure (thickness, surface area and volume). We identified 94 trait-ROI significant associations, and 307 distinct cluster of vertex-associations, which partly overlap the ROI associations. For AD versus controls, smaller hippocampus, amygdala and of the medial temporal lobe (fusiform and parahippocampal gyri) was confirmed and the vertex-wise results provided unprecedented localisation of some of the associated region. We replicated AD associated differences in several subcortical (putamen, accumbens) and cortical regions (inferior parietal, postcentral, middle temporal, transverse temporal, inferior temporal, paracentral, superior frontal). These grey-matter regions and their relative effect sizes can help refine our understanding of the brain regions that may drive or precede the widespread brain atrophy observed in AD. An AD grey-matter score evaluated in independent cohorts was significantly associated with cognition, MCI status, AD conversion (progression from cognitively normal or MCI to AD), genetic risk, and tau concentration in individuals with none or mild cognitive impairments (AUC in 0.54–0.70, p-value < 5e-4). In addition, some of the grey-matter regions associated with cognitive impairment, progression to AD (‘conversion’), and cognition/functional scores were also associated with AD, which sheds light on the grey-matter markers of disease stages, and their relationship with cognitive or functional impairment. Our multi-cohort approach provides robust and fine-grained maps the grey-matter structures associated with AD, symptoms, and progression, and calls for even larger initiatives to unveil the full complexity of grey-matter structure in AD.
UR - https://www.scopus.com/pages/publications/85217572305
U2 - 10.1002/hbm.70089
DO - 10.1002/hbm.70089
M3 - Article
C2 - 39907291
SN - 1065-9471
VL - 46
JO - Human brain mapping
JF - Human brain mapping
IS - 2
M1 - e70089
ER -