Rostral associations of MRI atrophy of the amygdala and entorhinal cortex across the AD spectrum

This paper examines associations of atrophy in the amygdala, entorhinal cortex and hippocampus based on magnetic resonance imaging (MRI) and Positron Emission Tomography (PET) scans from two independent cohorts: Alzheimer's Disease Neuroimaging Initiative (ADNI) and Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD) study. The amygdala, entorhinal cortex (ERC) and transentorhinal cortex (TEC) are shown to change earlier in the disease than the hippocampus based on volume atrophy rate. Over four hundred laminar reconstructions showed that ERC/TEC volume loss is linked to cortical thinning, as a more specific measure historically linked to the layer-specific pattern of tau pathology deposition. Additionally, high-field atlasing with delineations of amygdala subregions shows predominant volume loss in medial subregions including basomedial, basolateral, and corticocentromedial amygdala compared with the lateral subregion. Consistent with prior studies linking MRI-derived atrophy to hyperphosphorylated tau deposition in the amygdala and ERC/TEC, the atrophy rate marker demonstrates strong associations with tau PET measures and spatial co-localization with tau pathology.