Amygdala Subregional Atrophy Across ATN-Defined Mild Cognitive Impairment Subgroups

Background: Alzheimer’s disease (AD) pathology begins years before clinical symptoms, with Mild Cognitive Impairment (MCI) as a prodromal stage. The ATN framework (Amyloid, Tau, Neurodegeneration) aids in stratifying MCI risk. While amygdala atrophy is a recognized biomarker, amygdala subregional changes across ATN-defined MCI subgroups remain underexplored. Methods: This study analyzed MRI data and cerebrospinal fluid biomarkers from 134 MCI participants classified into A–T–, A+T–, and A+T+ subgroups using ADNI data. Amygdala volumes were computed and compared among the different groups. Furthermore, we also investigated the relationship between the altered brain regions and cognitive function. Results: Significant atrophy was observed in the A+T+ group within bilateral basal, accessory basal, central nuclei, and right cortical-amygdaloid transition area compared to other groups. Volume reductions in the left central nucleus correlated positively with cognitive scores. Conclusion: Amygdala subregional atrophy, particularly in the central, basal, accessory basal, and cortical-amygdaloid transition nuclei, is linked to AD pathology progression and cognitive decline. The findings suggested the right amygdala’s vulnerability and suggest these subregions as potential early imaging biomarkers for AD progression.