Volume changes of hippocampal and amygdala subfields in patients with mild cognitive impairment and Alzheimer's disease

Abstract

Background: Automated segmentation of hippocampal and amygdala subfields could improve classification accuracy of Mild Cognitive Impairments (MCI) and Alzheimer's Disease (AD) individuals.

Methods: We applied T1-weighted magnetic resonance imaging (MRI) for 21 AD, 39 MCI and 32 normal control (NC) participants at 3-Tesla MRI. Twelve hippocampal subfields and 9 amygdala subfields in each hemisphere were analyzed using FreeSurfer 6.0.

Results: Smaller volumes were observed in right/left whole hippocampus, right/left hippocampal tail, right/left subiculum, right Cornu ammonis 1(CA1), right/left molecular layer, right granule cell-molecular layer-dentate gyrus (GC-ML-DG), right CA4, right fimbria, right whole amygdala, right/left accessory basal, right anterior amygdala area, left central, left medial and right/left cortical nucleus of AD group compared to both MCI and NC groups (p < 0.001). The volumes of right presubiculum, right CA3, right hippocampus-amygdala-transition-area (HATA), right lateral, right basal, right central, right medial, right cortico-amygdaloid transition (CAT) and right paralaminar nucleus were significantly larger in NC than AD group (p ≤ 0.001), while the volumes of right subiculum, right CA1, right molecular layer, right whole hippocampus, right whole amygdala, right basal and right accessory basal were significantly larger in NC than MCI group (p ≤ 0.002). Trend analysis showed that most hippocampus and amygdala subfields have a trend of atrophy with the decline of cognitive function. Six core components were identified by the hierarchical clustering. The combined Receiver operating characteristic (ROC) analysis achieved the diagnostic performances (AUC: 0.81) in differentiating AD from MCI; (AUC: 0.79) in differentiating MCI from NC and (AUC: 0.97) in differentiating AD from NC.

Conclusions: Volumetric differences of hippocampus and amygdala were at a finer subfields scale, and the volumes of right basal nucleus, left parasubiculum, left medial nucleus, left GC-ML-DG, left hippocampal fissure, and right fimbria can be employed as neuroimaging biomarkers to assist the clinical diagnosis of MCI and AD.

Keywords: Alzheimer’s disease; Amygdala; Automated segmentation method; Hippocampus; Mild cognitive impairment.