Distinct morphological patterns of the hippocampus and amygdala in normal and pathological aging

Background: Normal aging is accompanied by cognitive decline and structural changes in the brain, most notably within the hippocampus and amygdala. However, distinguishing these age-related alterations from the earliest signs of neurodegenerative disorders remains challenging. Objective: This study aims to investigate and compare the alteration patterns of hippocampus and amygdala during normal aging and in cases of mild cognitive impairment (MCI) and Alzheimer's disease (AD), which will provide insights into their distinct structural profiles. Methods: A total of 2195 participants aged 20–90 from three public cohorts (1364 cognitively normal controls, 623 MCI, and 208 AD) were grouped by decade to examine age- and disease-related differences in surface-based morphometry of hippocampus and amygdala. Radial distance, tensor-based morphometry, and multivariate tensor-based morphometry were calculated and combined to generate the Multivariate Morphometry Statistics, which capture both radial and tangential deformations at each vertex. Statistical and deformation analyses were further performed to identify the alteration patterns across 15000 surface vertices between age groups. Results: In healthy adults, significant intergroup differences were observed in the hippocampal CA1 and subiculum, as well as in the lateral, basolateral, and accessory basal nuclei of the amygdala. In MCI and AD, additional significant differences were detected in the hippocampal CA2–3 subfield and the central, medial, and cortical nuclei of the amygdala. Conclusions: We provide a surface-based morphometry map of the hippocampus and amygdala across age groups in normal and pathological aging, revealing distinct morphological patterns that enhance understanding of aging and neurodegeneration.