Amyloidosis and neurodegeneration result in distinct structural connectivity patterns in mild cognitive impairment

Publication date: Available online 5 April 2017
Source:Neurobiology of Aging
Author(s): Thomas Jacquemont, Fabrizio De Vico Fallani, Anne Bertrand, Stéphane Epelbaum, Alexandre Routier, Bruno Dubois, Harald Hampel, Stanley Durrleman, Olivier Colliot
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 four 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 bi-hemispheric 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 two AD biomarkers induces a connectome alteration that is maximal when they co-exist.



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