Analysis of Metric Distances and Volumes of Hippocampi Indicates Different Morphometric Changes over Time in Dementia of Alzheimer Type and Nondemented Subjects

Abstract

In this article, we analyze the morphometry of hippocampus in subjects with very mild dementia of Alzheimer's type (DAT) and nondemented controls and how it changes over a two-year period. Morphometric differences with respect to a template hippocampus were measured by the metric distance obtained from the Large Deformation Diffeomorphic Metric Mapping (LDDMM) algorithm which was previously used to calculate dense one-to-one correspondence vector fields between the shapes. LDDMM assigns metric distances on the space of anatomical images thereby allowing for the direct comparison and quantization of morphometric changes. We use various statistical methods to compare the metric distances in a cross-sectional and longitudinal manner. At baseline, the metric distances for demented subjects are found not to be significantly different from those for nondemented subjects. At follow-up, the metric distances for demented subjects were significantly larger compared to nondemented subjects. The metric distances for demented subjects increased significantly from baseline to follow-up but not for nondemented subjects. We also use the metric distances in logistic regression for diagnostic discrimination of subjects. We compare metric distances with the volumes and obtain similar results. In classification, the model that uses volume, metric distance, and volume loss over time together performs better in detecting DAT. Thus, metric distances with respect to a template computed via LDDMM can be a powerful tool in detecting differences in shape in cross-sectional as well as longitudinal studies.