Psychiatry Res. 2015 Apr 30;232(1):71-5. doi: 10.1016/j.pscychresns.2015.01.018.

Comparison of regional gray matter volume abnormalities in Alzheimer׳s disease and late life depression with hippocampal atrophy using VSRAD analysis: a voxel-based morphometry study.

Shimoda K1, Kimura M2, Yokota M2, Okubo Y3.
  • 1Department of Psychiatry, Nippon Medical School Chiba Hokuso Hospital, Chiba, Japan. Electronic address: kshimoda@nms.ac.jp.
  • 2Department of Psychiatry, Nippon Medical School Chiba Hokuso Hospital, Chiba, Japan.
  • 3Department of Psychiatry, Nippon Medical School, Tokyo, Japan.

 

Abstract

Previous voxel-based morphometry (VBM) studies revealed that hippocampal volume loss in patients with late life depression (LLD) is associated with cognitive impairment and a higher risk for dementia. However, LLD patients can experience hippocampal atrophy without cognitive impairment. Thus, while LLD and AD can show comparable hippocampal atrophy, they may encompass different neuropathological changes. Using VBM, we therefore investigated differences in regional gray matter changes in 17 late-onset LLD patients and 21 AD patients (without a history of LLD) who exhibited comparably severe atrophy of the entorhinal cortex and the parahippocampal gyrus on MRI scans for voxel-based specific regional analysis system for AD (VSRAD). Relative to the VSRAD database for healthy individuals, significant atrophy was observed in mesial temporal lobe structures and the anterior cingulate cortex in both groups. Atrophy of the posterior cingulate cortex and precuneus was observed only in the AD group. Comparisons of gray matter volume by multivariate analysis of variance revealed significantly reduced volume of the right middle and inferior temporal gyrus, uncus, posterior cingulate cortex, and precuneus in the AD group only, suggesting impairment of different networks in AD and LLD. Indeed, structural changes in the posterior part of the default-mode network are believed to be associated with cognitive impairments specific to AD.

KEYWORDS: Alzheimer׳s disease; Anterior and posterior default mode network; Hippocampal atrophy; Late life depression; VSRAD; Voxel-based morphometry

PMID: 25773003

 

Supplements:

There appears to be a general consensus that in a subset of LLD patients, there is a reduction in the volume of brain regions that are affected early in Alzheimer’s disease (AD), including frontal and medial temporal lobe (MTL) structures (Sexton et al., 2012). While there are several lines of evidence that link hippocampal atrophy to AD, the cause of hippocampal atrophy in late-onset LLD and its relationship to AD has not yet been determined. The voxel-based specific regional analysis system for AD (VSRAD), which targets the MTL, was developed as a sensitive diagnostic tool to detect early stages of AD (Matsuda et al., 2013). The VSRAD enabled the evaluation of the degree of entorhinal cortex and parahippocampal volume loss by comparing a given a subject’s gray matter (GM) volume to that of the original healthy individual database template. Thus, in this study, we compared regional GM volume abnormalities in AD to those observed in late-onset LLD, using VSRAD. It is thought that the degree of atrophy of MTL structures is generally connected with the grade of memory impairment. However, because the cause of the atrophy of the hippocampus in LLD was not clear in the present cases, where the grade of degeneration of MTL structures coincided with that found in AD, we predicted that there would be neuropathologically different features between LLD and AD, even when the degree of hippocampal atrophy between the two diseases was comparable. The Z-score map indicates GM volume reduction obtained and compares the mean image of the healthy control group and the mean image of each group using the VSRAD shown in Figure 1. Significant atrophy was observed in mesial temporal lobe structures, including the entorhinal cortex, hippocampus and amygdala, the orbitofrontal cortex, and the anterior cingulate cortex, in both patient. Significant atrophy of the posterior cingulate cortex, precuneus and right cerebellum was found only in the AD patient (Figure 1). Next, we compared the gray matter volume in the LLD group and the AD group. An automated atlas-based VOI analysis method revealed a significant reduction in gray matter volume in the right and left precuneus, the right middle and inferior temporal gyrus, the uncus, and the PCC region in the AD group compared with the LLD group. On the other hand, no specific gray matter volume was found to be significantly decreased in the LLD group relative to the AD group. Our study revealed structural changes in the anterior DMN in both the AD and LLD groups, whereas structural changes in the posterior DMN were only observed in the AD group.

These findings were consistent with our results obtained using atlas-based VBM. Significantly decreased gray matter volume in the precuneus and PCC regions was seen in the AD group relative to the LLD group. The late-onset LLD group exhibited morphological changes different from those observed in AD, supporting the results from previous VBM studies. Importantly, because LLD is a collection of heterogeneous disorders, atrophy of the hippocampus does not necessarily suggest an association with AD.

 

image description

Figure 1. Z score map of gray matter volume reductions in LLD and AD using VSRAD. VSRAD provides a color-scaled Z score map ranging from 2.0 to 6.0 with overlaid orthogonal sections of an anatomically standardized brain template. Significant atrophy of the posterior cingulate cortex, and precuneus was found only in the AD patient (Purple circles indicate the VOI of VSRAD)

 

References

  • Sexton, C.E., Allan, C.L., Le Masurier, M., McDermott, L.M., Kalu, U.G., Herrmann, L.L., Mäurer, M., Bradley, K.M., Mackay, C.E., Ebmeier, K.P. 2012. Magnetic resonance imaging in late-life depression: multimodal examination of network disruption. Archives of General Psychiatry 69, 680-689.
  • Matsuda, H., Mizumura, S., Nemoto, K., Yamashita, F., Imabayashi, E., Sato, N., Asada, T. 2012. Automatic voxel-based morphometry of structural MRI by SPM8 plus diffeomorphic anatomic registration through exponentiated lie algebra improves the diagnosis of probable Alzheimer Disease. American Journal of Neuroradiology 33, 1109-1114

 

Contact:

Kengo Shimoda M.D.,

Senior Assistant Professor, Department of Psychiatry, Nippon Medical School, Chiba Hokuso Hospital, 1715 Kamagari, Inzai, Chiba 270-1694, Japan, Tel: +81-476-99-1111, Fax: +81-476-99-1926, Email: kshimoda@nms.ac.jp

 

 

 

 

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