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: Alzheimers Disease Neuroimaging Initiative (ADNI) and Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD) study. The amygdala and entorhinal cortex (ERC) are shown to change earlier in the disease than the hippocampus based on atrophy of laminar thickness of the ERC and amygdala volumes. Over four hundred laminar reconstructions showed that ERC 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 compared with the lateral subregion. In the context of earlier work linking MRI-based atrophy with hyperphospho-rylated tau deposition in the ERC and amygdala, the atrophy rate marker is shown to be strongly associated with tau deposition as measured by tau positron emission tomography imaging and co-localization of the atrophy marker to the spatial distribution of tau deposition. HighlightsO_LIStructural MRI analyses across ADNI and BIOCARD cohorts reveal significantly greater early atrophy in amygdala and entorhinal cortex (ERC), marking them as sensitive indicators of preclinical Alzheimers disease. C_LIO_LIERC volume loss is shown to correspond to cortical laminar thinning by surface-based diffeomorphic reconstructions, confirming MRI volume atrophy as a biologically valid marker of early neuronal degeneration. C_LIO_LIPredominant atrophy in medial amygdala subregions (basomedial, basolateral, corticocentromedial) are identified compared to the lateral amygdala using high-field (11T) atlases, mirroring known histopathological tau distribution. C_LIO_LIMRI volume atrophy correlates with tau burden measured by tau PET imaging, demonstrating region-specific correspondence between structural atrophy and molecular pathology. C_LI