Journal
NEUROBIOLOGY OF AGING
Volume 55, Issue -, Pages 177-189Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2017.03.023
Keywords
Alzheimer's disease; MCI; Biomarkers; Structural connectome; Network analysis
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Funding
- Investissements d'avenir (Agence Nationale de la Recherche-10-IA Agence Institut Hospitalo-Universitaire-6) [ANR-10-IAIHU-06]
- Contrat d'Interface Local from Assistance Publique-Hopitaux de Paris (AP-HP)
- AXA Research Fund
- Fondation Universite Pierre et Marie Curie
- Fondation pour la Recherche sur Alzheimer, Paris, France
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Alzheimer's disease (AD) is increasingly considered as a disconnection syndrome. Previous studies of the structural connectome in early AD stages have focused on mild cognitive impaired subjects (MCI), considering them as a homogeneous group. We studied 168 subjects from the Alzheimer's Disease Neuroimaging Initiative database (116 MCI and 52 cognitively normal subjects). Biomarker-based stratification using amyloid biomarkers (AV45 PET) and neurodegeneration biomarkers (MRI and FDG PET) led to 4 subgroups based on amyloid positivity (A+/-) and neurodegeneration positivity (N+/-): A -N-, A+N-, A-N+, and A+N+. Using diffusion MRI, we showed that both MCI A-N+ and MCI A+N+ subjects displayed an alteration of the white matter in the fornix and a significant bihemispheric network of decreased connections. These network alterations in MCI A+N+ are stronger and more focal than those of MCI A-N+. Only MCI A+N+ subjects exhibited specific changes in hippocampal connectivity and an AD-like alteration pattern. Our results indicate that the connectome disintegration pattern of MCI subgroups differ with respect to brain amyloid and neurodegeneration. Each of these 2 AD biomarkers induces a connectome alteration that is maximal when they coexist. (C) 2017 Elsevier Inc. All rights reserved.
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