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

Thomas Jacquemont (1, 2) , Fabrizio de Vico Fallani (1, 2) , Anne Bertrand (3, 1, 2) , Stéphane Epelbaum (4, 1, 2) , Alexandre Routier (1, 2) , Bruno Dubois (1, 4) , Harald Hampel (1, 4) , Stanley Durrleman (2, 1) , Olivier Colliot (3, 1, 2, 4)

1 ICM - Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute
2 ARAMIS - Algorithms, models and methods for images and signals of the human brain = Algorithmes, modèles et méthodes pour les images et les signaux du cerveau humain [ICM Paris]
3 CHU Pitié-Salpêtrière [AP-HP]
4 IM2A - Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre]

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.

Mots clés: Biomarkers; Alzheimer's disease; MCI; Network analysis; Structural connectome

Domaines: Traitement du signal et de l'image [eess.SP]; Vision par ordinateur et reconnaissance de formes [cs.CV]; Imagerie médicale; Traitement des images [eess.IV]; Imagerie; Neurobiologie

Thomas Jacquemont, Fabrizio de Vico Fallani, Anne Bertrand, Stéphane Epelbaum, Alexandre Routier, et al.. Amyloidosis and neurodegeneration result in distinct structural connectivity patterns in mild cognitive impairment. Neurobiology of Aging, 2017, ⟨10.1016/j.neurobiolaging.2017.03.023⟩. ⟨hal-01518785⟩