Morphological and Microstructural Changes of the Hippocampus in Early MCI: A Study Utilizing the Alzheimer's Disease Neuroimaging Initiative Database

ABSTRACT

BACKGROUND AND PURPOSE: With the aim of facilitating the early detection of Alzheimer's disease, the Alzheimer's Disease Neuroimaging Initiative proposed two stages based on the memory performance early mild cognitive impairment (EMCI) and late mild cognitive impairment (LMCI). The current study was designed to investigate structural differences in terms of surface atrophy and microstructural changes of the hippocampus in EMCI and LMCI. METHODS: Hippocampal shape modeling based on progressive template surface deformation was performed on T1-weighted MRI images obtained from 20 cognitive normal (CN) subjects, 17 EMCI patients, and 20 LMCI patients. A template surface in CN was used as a region of interest for diffusion-tensor imaging (DTI) voxel-based morphometry (VBM) analysis. Cluster-wise group comparison was performed based on DTI indices within the hippocampus. Linear regression was performed to identify correlations between DTI metrics and clinical scores. RESULTS: The hippocampal surface analysis showed significant atrophies in bilateral CA1 regions and the right ventral subiculum in EMCI, in contrast to widespread atrophy in LMCI. DTI VBM analysis showed increased diffusivity in the CA2–CA4 regions in EMCI and additionally in the subiculum region in LMCI. Hippocampal diffusivity was significantly correlated with scores both for the Mini Mental State Examination and on the Modified Alzheimer Disease Assessment Scale cognitive subscale. However, the hippocampal diffusivity did not vary significantly with the fractional anisotropy. CONCLUSIONS: EMCI showed hippocampal surface changes mainly in the CA1 region and ventral subiculum. Diffusivity increased mainly in the CA2–CA4 regions in EMCI, while it decreased throughout the hippocampus in LMCI. Although axial diffusivity showed prominent changes in the right hippocampus in EMCI, future studies need to confirm the presence of this laterality difference. In addition, diffusivity is strongly correlated with the cognitive performance, indicating the possibility of using diffusivity as a biomarker for disease progression.