Shape changes in the CA3 and dentate regions of the hippocampus in individuals with mild cognitive impairment

Abstract

Background: Shape and volume changes in the subfields in the hippocampus have been reported in MCI patients and have been shown to predict whether or not patients decline. Previous studies that reported shape changes in the CA1 region of the hippocampus did not segment the individual subfields of the hippocampus, thus these deflections could indeed be due to shape changes in the deeper subfields. More recent reports suggest that there may be shape and volume changes in the CA3 and dentate gyrus (DG) regions of the hippocampus that may differentiate healthy adults from those early in the course of AD or in some cases in asymptomatic carriers of the ApoE e4 gene. We sought to investigate the detailed profile of volume and shape changes in MCI patients (all CDR 0.5) using the OASIS (Open Access Series of Imaging Studies) freely available data set. Methods: We used an alternative approach to previous studies by combining traditional grayscale data with manual segmentations of the subfields. In this technique, we manually segmented hippocampal subfields on each individual scan and used a region-of-interest based diffeomorphic alignment technique (ROI-ANTS) that we recently developed in order to quantify each subfield’s shape changes. The method uses information from grayscale images but weights the transformations based on ROI segmentations, resulting in optimum cross-participant overlap. Results: We found significant shape changes in the deeper subfields (CA3/DG) in MCI patients compared to age and gender matched controls, suggesting that this is one of the first hippocampal regions that deteriorates in the course of AD and that previously studies likely underestimated the extent to which it was involved due to an inherent bias in the alignment techniques. Conclusions: Using a robust diffeomorphic technique and precise anatomical segmentations, we find evidence for shape changes in the CA3/DG that may precede other hippocampal changes very early in the course of AD. This is consistent with animal studies suggesting that loss of synaptic input into the DG early in AD may result in shape changes in this region. This can potentially be a viable biomarker for predicting AD onset.