DIFFERENT STRUCTURAL CONNECTIVITY PATTERNS IN MILD COGNITIVE IMPAIRMENT STRATIFIED BY AMYLOID AND NEURODEGENERATION BIOMARKERS

Abstract

Alzheimer's disease (AD) is associated to disruption of anatomical connectivity. Previous studies of structural connectivity in early AD stages have focused on mild cognitive impaired (MCI) subjects without disentangling the heterogeneity of the group. We studied 116 MCI patients and 52 cognitively normal (CN) subjects from the Alzheimer's Disease Neuroimaging Initiative database. We distinguished four groups of MCI using amyloid (AV45 PET scan) and neurodegeneration biomarkers (MRI and 18Fluorodeoxyglucose PET scan), including MCI A+N+ (positive for both amyloid and neurodegeneration), and MCI A-N+ (positive for neurodegeneration but negative for amyloid) also called SNAP. For each subject, we computed mean fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) over anatomical tracts and built structural connectivity graphs. Only MCI A+N+ subgroup displayed an AD-like disconnection pattern (alteration of the fornix mean FA and MD and the cingulum mean MD, disconnection of middle temporal gyrus and increase of hippocampal clustering coefficient). MCI A+N- displayed, as MCI A+N+, a bilateral alteration of the tapetum mean FA which appear to be specific of amyloid positive MCI subgroups. As MCI A+N+, MCI A-N+ displayed a fornix and cingulum FA and MD alteration but no hippocampus topology changes. MCI A-N+ were also characterized by a wide but weak impaired module. Contrary to the other MCI subgroups, MCI A-N- did not display white matter alterations and only a small impaired module compare to CN A-N-.