Abnormalities of hippocampal surface structure in very mild dementia of the Alzheimer type

Abstract

To better define the pattern of hippocampal deformity early in the course of Alzheimer's disease, we compared the pattern of hippocampal surface variation in subjects with very mild dementia of the Alzheimer type (DAT) and nondemented subjects. The surface of the hippocampus was divided a priori on a neuroanatomical template into three zones approximating the locations of underlying subfields [Csernansky, J.G., Wang, L., Swank, J., Miller, J.P., Gado, M., McKeel, D., Miller, M.I., Morris, J.C., 2005. Preclinical detection of Alzheimer's disease: hippocampal shape and volume predict dementia onset in the elderly. NeuroImage 25, 783-792]; i.e., a lateral zone (LZ) approximating the CA1 subfield, a superior zone (SZ) approximating the combined CA2, CA3, CA4 subfields and the gyrus dentatus (GD), and an inferior-medial zone (IMZ) approximating the subiculum. Large-deformation high-dimensional brain mapping (HDBM-LD) was used to generate the hippocampal surfaces of all subjects and to register the surface zones across subjects. Average variations within each zone were calculated for the subjects with very mild DAT as compared to the average of the nondemented subjects. After correcting for multiple comparisons, the very mild DAT subjects showed significant inward variation in the left and right LZ, the left and right IMZ, but not in the left and right SZ as compared to nondemented subjects. In logistic regression analyses, inward variation of the left and right LZ or IMZ by 0.1 mm relative to the average of the nondemented subjects increased the odds of the subject being a very mild DAT subject (range-1.18 to 1.57) rather than being a nondemented subject. The odds ratios for the left and right SZ were not significant. These results represent a replication of our previous findings [Csernansky, J.G., Wang, L., Joshi, S., Miller, J.P., Gado, M., Kido, D., McKeel, D., Morris, J.C., Miller, M.I., 2000. Early DAT is distinguished from aging by high-dimensional mapping of the hippocampus. Neurology 55, 1636-1643.] and suggest that inward deformities of the hippocampal surface in proximity to the CA1

Detection of prodromal Alzheimer's disease via pattern classification of magnetic resonance imaging

“…These structures merit further investigation using imaging methods that are more suitable for analysis of white matter structure, especially diffusion tensor imaging. Finally, our results indicated bilateral hippocampal atrophy, in contrast to recent reports of lateralized atrophy, with both greater right hippocampal atrophy [48] and greater left hippocampal atrophy [27] reported.…”

“…A relatively higher CA1 atrophy would also agree with histopathological studies [49], albeit the resolution of current 1.5T MR images does not allow us to specifically define hippocampal subfields. Some recent studies using high-dimensional warping of the hippocampus have also observed spatially heterogeneous patterns of hippocampal atrophy in AD [19,48]. These results further bolster our confidence that sophisticated methods for feature selection and pattern classification are necessary to capture the complex patterns of brain atrophy that are most informative for diagnosis, whereas conventional ROI volumetric analysis is limited in that it combines regions that are relatively more affected by disease with regions that are relatively less affected, thereby potentially reducing the predictive power of these measurements.…”

“…Brain atrophy in the early stages of AD may be relatively subtle and spatially distributed over many brain regions [6,7,15,28,30], including the entorhinal cortex, the hippocampus, lateral and inferior temporal structures, anterior and posterior cingulate, and possibly other regions that have only recently been investigated [38]. Furthermore, spatially heterogeneous patterns of atrophy have been found within the hippocampus, with regions known to correspond to the CA1 field presenting relatively more pronounced atrophy [19,48]. Patterns of atrophy associated with pathology are confounded by complex patterns of atrophy associated with normal aging [43].…”

P2‐231: Systematic Comparison of Different Techniques to Measure Hippocampal Subfield Volumes in ADNI2

“…The intra-class correlation coefficients of the areas of the three surface zones were between 0.90 and 0.97 (Wang et al 2006).…”

“…These techniques were applied to a variety of diseases in small single-site studies and usually found subfield volumetry to be superior to standard whole hippocampal volumetry for the detection of hippocampal damage in the early stages of the disease process, for differentiating between diseases or for the investigation of structure/function relationships (e.g., Wang et al, 2006;Ballmaier et al, 2008;Mueller et al, 2008;Schobel et al, 2009;Neylan et al, 2010;Bender et al, 2013;Kerchner et al, 2014;SchoeneBake et al, 2014;Chao et al, 2014;Hsu et al, 2015;De Flores et al, 2015;Pluta et al, 2012;Yushkevich et al, 2015b). The promise of hippocampal subfield volumetry techniques however led to two unexpected developments that could potentially limit the usefulness of this approach.…”