Differential hippocampal shapes in posterior cortical atrophy patients: A comparison with control and typical AD subjects

Abstract

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by predominant visual deficits and parieto-occipital atrophy, and is typically associated with Alzheimer's disease (AD) pathology. In AD, assessment of hippocampal atrophy is widely used in diagnosis, research, and clinical trials; its utility in PCA remains unclear. Given the posterior emphasis of PCA, we hypothesized that hippocampal shape measures may give additional group differentiation information compared with whole-hippocampal volume assessments. We investigated hippocampal volume and shape in subjects with PCA (n = 47), typical AD (n = 29), and controls (n = 48). Hippocampi were outlined on MRI scans and their 3D meshes were generated. We compared hippocampal volume and shape between disease groups. Mean adjusted hippocampal volumes were ∼ 8% smaller in PCA subjects (P < 0.001) and ∼ 22% smaller in tAD subject (P < 0.001) compared with controls. Significant inward deformations in the superior hippocampal tail were observed in PCA compared with controls even after adjustment for hippocampal volume. Inward deformations in large areas of the hippocampus were seen in tAD subjects compared with controls and PCA subjects, but only localized shape differences remained after adjusting for hippocampal volume. The shape differences observed, even allowing for volume differences, suggest that PCA and tAD are each associated with different patterns of hippocampal tissue loss that may contribute to the differential range and extent of episodic memory dysfunction in the two groups.

Keywords: Alzheimer; Alzheimer's disease; PCA; atrophy; classifier; hippocampus; morphometry; shape; support vector machine.

Figure 1

Hippocampal shape difference after adjusting for age, gender, and TIV in (a) PCA vs. controls, (b) tAD vs. Controls, (c) PCA vs. tAD. The color scale for statistical difference represents the FWE‐error corrected P‐values at a threshold of P = 0.05. Blue indicates areas where there was an inward deformation in (a) PCA as compared to tAD, (b) tAD as compared to controls, (c) PCA as compared to tAD whereas red/yellow indicates areas where there was an outward deformation. A = anterior, P = Posterior. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 2

Hippocampal shape difference after adjusting for age, gender, and hippocampal volume in (a) PCA vs. controls, (b) tAD vs. Controls, (c) PCA vs. tAD. The color scale for statistical difference represents the FWE‐error corrected P‐values at a threshold of P = 0.05. Blue indicates areas where there was an inward deformation in (a) PCA as compared to tAD, (b) tAD as compared to controls, (c) PCA as compared to tAD whereas red/yellow indicates areas where there was an outward deformation. A = anterior, P = Posterior. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 3

Hippocampal shape difference in PCA vs. tAD after adjusting for (a) age, gender, MMSE score, disease duration, and head size and (b) age, gender, MMSE score, disease duration, and hippocampal volume. The color scale for statistical difference represents the FWE‐error corrected P‐values at a threshold of P = 0.05. Blue indicates areas where there was an inward deformation in PCA as compared to tAD whereas red/yellow indicates areas where there was an outward deformation. A = anterior, P = Posterior. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure A1

Summary of shape analysis procedure: (a) Hippocampi are segmented, holes filled and minimal smoothing applied, (b) raw surface meshes generated and spherical parameterizations are computed, (c) triangulated surface meshes are computed from spherical parameterizations, (d) surface meshes aligned (translation and rotation), (e) distance between mean mesh and individual meshes at each vertice is calculated, (f) statistical comparisons performed. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure B1

Nested 10‐fold cross‐validation procedure used for model tuning and evaluation. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]