Morphology of the inner structure of the hippocampal formation in Alzheimer disease

Abstract

Background and purpose: To our knowledge, inner structural alterations of the hippocampus have never been demonstrated because of the lack of contrast between the hippocampus proper and the superficial medullary lamina. We sought to demonstrate the anatomic details of the inner hippocampus and to elucidate its alterations in Alzheimer disease (AD) in vivo.

Methods: We obtained multishot diffusion- and T2-weighted MR images in 14 healthy control subjects and 26 patients with mild or moderate AD (diagnosis based on Mini-Mental Status Examination scores). We measured the width of the subiculum, CA1 and CA3-4, and the height of CA3-4 on coronal images.

Results: The subiculum and hippocampus proper were demonstrated as whirlpool-shaped hyperintense areas, and the superficial medullary lamina was visible as a hypointense structure along the inner margin of the hippocampus proper. Regarding the width of the subiculum and CA1, intergroup analysis revealed significant differences between the control and mild or moderate AD groups. In the width of CA3-4, we found no significant difference between the control and mild AD groups; however, differences between the control and moderate AD groups and between the mild and moderate AD groups were significant. In the height of CA3-4, we observed no significant differences between groups.

Conclusion: We clearly visualized the inner structure of the hippocampal formation by using multishot diffusion-weighted imaging. The subiculum and CA1 are the most vulnerable regions in AD, and atrophy of these structures was evident in both mild and moderate AD.

Fig 1.

Coronal photomicrographs of normal and atrophic hippocampus (Klüver-Barrera stain). A, Image in a 56-year-old man with dentatorubro-pallidoluysian atrophy shows no atrophy of the left subiculum or hippocampus proper. Image represents a normal hippocampus. The hippocampus proper consists of the CA1, CA2, CA3, and CA4 fields. Bar indicates 1 mm. B, Image in a 78-year-old man with AD (duration of illness, 15 years) shows severe atrophy of the subiculum (arrow). The superficial medullary lamina (arrowheads) is thinner than that of a normal hippocampus. Bar indicates 1 mm. C, Magnified (×200) view of the image in A shows numerous nerve fibers running in the anteroposterior direction in the superficial medullary lamina of the hippocampal formation.

Fig 2.

Schematic representation of the hippocampal formation shows the measurement points for the subiculum and the hippocampus proper. PHG indicates the parahippocampal gyrus.

Fig 3.

Coronal MR images in a 59-year-old man (control subject). A, Multishot diffusion-weighted image clearly shows the inner structure of the left hippocampus. The subiculum (left arrowhead), CA1 of the hippocampus proper (right arrowhead), and CA3–4 (top arrow) are demonstrated as hyperintense areas, and the superficial medullary lamina (bottom arrow) is shown as a hypointense area. B, T2-weighted image faintly shows the subiculum (arrowhead), the hippocampus proper, and the superficial medullary lamina (arrow).

Fig 4.

MR images in a 71-year-old woman with mild AD (MMSE score, 27; duration of illness, 2 years). A, Multishot diffusion-weighted coronal image shows atrophic subiculum (left arrowhead) and CA1 (right arrowhead). However, the CA3–4 (arrow) is spared. B, T2-weighted image scarcely demonstrates the inner structure of the left hippocampus (arrow).

Fig 5.

MR images in a 68-year-old man with mild AD (MMSE score, 25; duration of illness, 3 years). A, Multishot diffusion-weighted coronal image shows an atrophic subiculum (left arrowhead) and CA1 (right arrowhead). CA3–4 (arrow) is spared. B, T2-weighted image scarcely demonstrates the inner structure of the left hippocampus (arrow).

Fig 6.

MR images in a 64-year-old woman with moderate AD (MMSE score, 8; duration of illness, 12 years). A, Multishot diffusion-weighted coronal image shows an atrophic subiculum (left arrowhead). CA1 (right arrowhead) is comparatively spared; however, CA3–4 (arrow) is atrophic. B, T2-weighted image scarcely demonstrates the inner structure of the left hippocampus (arrow).

Fig 7.

MR images in a 71-year-old woman with moderate AD (MMSE score, 6; duration of illness, 11 years). A, Multishot diffusion-weighted coronal image shows severe atrophy of the subiculum (left arrowhead) and CA3–4 (small arrow). Atrophy of CA1 (right arrowhead) is mild. Image also shows atrophy of the parahippocampal gyrus (large arrow). B, T2-weighted image barely shows the inner structure of the hippocampus (arrow).

Fig 8.

MR images in a 45-year-old man (control subject). A, Multishot diffusion-weighted coronal image clearly shows the inner structure of the left hippocampus: the subiculum (left arrowhead), CA1 of the hippocampus proper (right arrowhead), CA3–4 (small arrow), and the superficial medullary lamina (large arrow). B, T2-weighted coronal image faintly shows the superficial medullary lamina (arrow) as a hypointense area. C, T1-weighted 3D volumetric SPGR image (26/4.3; FOV, 18 cm; matrix, 256 × 256; thickness, 0.8 mm; slab, 64 mm) shows the superficial medullary lamina (arrow) as a hyperintense area and depicts it more faintly than does the T2-weighted image.