Abstract
Alzheimer’s disease is currently defined in molecular terms as the association of cortical amyloid and hyper-phosphorilated tau deposition. MRI biomarkers for AD capture neurodegenerative phenomena related to tissue loss, axonal damage, and synaptic loss but are blind to the underlying molecular pathology. On the other hand, neurodegenerative phenomena but not molecular pathology are closely related to clinical symptoms. Survey of the literature on structural MRI, diffusion MRI, and functional networks at rest including personal and international studies. Non topographic structural MRI markers are sensitive to AD even at the pre-dementia MCI stage, while diffusion and functional network markers at the asymptomatic stage. Topographic information enhance specificity, but is complicated by the heterogeneity of the topography of molecular pathology in AD (e.g. early onset AD being more often neocortical and late onset limbic). The association of MRI with molecular biomarkers also enhances specificity to very high figures at the MCI stage (>90%). The specificity of MRI AD-like biomarkers lies in their topography. Enhancement of specificity can be achieved through the association with either molecular markers or different MRI markers.
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