Voxel-based detection of white matter abnormalities in mild Alzheimer disease

Xie, Shusen; Xiao, Jiang; Gong, Guoliang; Zang, Yu‐Feng; Wang, Y. H.; Wu, Hong Kun; Jiang, Xiao Bing

doi:10.1212/01.wnl.0000219625.77625.aa

Cited by 195 publications

(176 citation statements)

References 30 publications

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“…The involvement of this tract as well as the CC, fornix, perforant path, and temporal WM is consistent with previous findings from DTI studies that reported diffusivity increases or anisotropy decreases in the same set of WM areas (Fellgiebel et al, 2004;Medina et al, 2006;Xie et al, 2006;Huang et al, 2007;Teipel et al, 2007;Zhang et al, 2007). Atrophy of the CC and perforant path have also already been highlighted in previous VBM studies of AD (Chaim et al, 2007) and MCI (Stoub et al, 2006), respectively.…”

Section: Discussionsupporting

confidence: 90%

Relationships between Hippocampal Atrophy, White Matter Disruption, and Gray Matter Hypometabolism in Alzheimer's Disease

Villain¹,

Desgranges²,

Viader³

et al. 2008

Journal of Neuroscience

338

243

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In early Alzheimer's disease (AD), the hippocampal region is the area most severely affected by cellular and structural alterations, yet glucose hypometabolism predominates in the posterior association cortex and posterior cingulate gyrus. One prevalent hypothesis to account for this discrepancy is that posterior cingulate hypometabolism results from disconnection from the hippocampus through disruption of the cingulum bundle. However, only partial and indirect evidence currently supports this hypothesis. Thus, using structural magnetic resonance imaging and 2-[ 18 F]fluoro-2-deoxy-D-glucose positron emission tomography in 18 patients with early AD, we assessed the relationships between hippocampal atrophy, white matter integrity, and gray matter metabolism by means of a whole-brain voxel-based correlative approach. We found that hippocampal atrophy is specifically related to cingulum bundle disruption, which is in turn highly correlated to hypometabolism of the posterior cingulate cortex but also of the middle cingulate gyrus, thalamus, mammillary bodies, parahippocampal gyrus, and hippocampus (all part of Papez's circuit), as well as the right temporoparietal associative cortex. These results provide the first direct evidence supporting the disconnection hypothesis as a major factor contributing to the early posterior hypometabolism in AD. Disruption of the cingulum bundle also appears to relate to hypometabolism in a large connected network over and above the posterior cingulate cortex, encompassing the whole memory circuit of Papez (consistent with the key location of this white matter tract within this loop) and also, but indirectly, the right posterior association cortex.

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Section: Discussionsupporting

confidence: 90%

Relationships between Hippocampal Atrophy, White Matter Disruption, and Gray Matter Hypometabolism in Alzheimer's Disease

Villain¹,

Desgranges²,

Viader³

et al. 2008

Journal of Neuroscience

338

243

View full text Add to dashboard Cite

show abstract

“…Indeed, some studies reported changes in the anterior subregion (e.g. [20,21,46,82]), some in the posterior subregion [20,21,83,91], and some found no callosal changes [40,85,92]. This inconsistency in results may be the consequence of reduced sample size of studies considering discrete diagnostic categories of different clinical stages.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the findings of studies on more homogeneous patients, such as those with mild AD, are discrepant. For example, Xie et al [82] found a decrease of FA in the genu and left anterior body of the CC, whereas Ulkmar et al [83] found a decrease of FA in the genu and splenium of the CC; other studies [84][85][86][87] found no differences in the CC in patients with mild AD.…”

Section: Diffusion-weighted Imaging and Diffusion Tensor Imaging Studiesmentioning

confidence: 98%

In Vivo Structural Neuroanatomy of Corpus Callosum in Alzheimer's Disease and Mild Cognitive Impairment Using Different MRI Techniques: A Review

Paola

Spalletta

Caltagirone

2010

JAD

129

103

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Abstract. The corpus callosum (CC), which connects the two cerebral hemispheres, is the largest white matter fiber bundle in the human brain. This structure presents a peculiar myelination pattern: it has small diameter fibers, located in the genu, which myelinate much later in normal development, and large diameter fibers of the splenium, which myelinate early in development. Although the pathology of AD mainly involves the cerebral gray matter structure, there is evidence that white matter may also be involved. To illustrate callosal white matter changes in AD pathology, in this review we summarize in vivo imaging studies in humans, focusing on region of interest, voxel-based morphometry, diffusion-weighted imaging, and diffusion tensor imaging techniques. Our aims were to identify where in the CC, when in the different stages of AD, and how callosal changes can be detected with different MRI techniques. Results showed that changes in the anterior (genu and anterior body) as well as in the posterior (isthmus and splenum) portions of the CC might already be present in the early stages of AD. These findings support the hypothesis that two mechanisms, Wallerian degeneration and myelin breakdown, might be responsible for the region-specific changes detected in AD patients. Wallerian degeneration affects the posterior CC subregion, which receives axons directly from those brain areas (temporo-parietal lobe regions) primarily affected by the AD pathology. Instead, the myelin breakdown process affects the later-myelinating CC subregion and explains the earlier involvement of the genu in CC atrophy.

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“…TBSS is a newer analytic technique developed to reduce the alignment and smoothing problems that have been reported with VBM (Smith et al, 2006(Smith et al, , 2007. Both approaches have been used to assess for differences in WM integrity in a variety of psychiatric disorders including MDD (Bae et al, 2006;Li et al, 2009;Xie et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Reconciling Variable Findings of White Matter Integrity in Major Depressive Disorder

Choi

Holtzheimer

Franco

et al. 2013

Neuropsychopharmacol

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Diffusion tensor imaging (DTI) has been used to evaluate white matter (WM) integrity in major depressive disorder (MDD), with several studies reporting differences between depressed patients and controls. However, these findings are variable and taken from relatively small studies often using suboptimal analytic approaches. The presented DTI study examined WM integrity in large samples of medication-free MDD patients (n ¼ 134) and healthy controls (n ¼ 54) using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) approaches, and rigorous statistical thresholds. Compared with health control subjects, MDD patients show no significant differences in fractional anisotropy, radial diffusivity, mean diffusivity, and axonal diffusivity with either the VBM or the TBSS approach. Our findings suggest that disrupted WM integrity does not have a major role in the neurobiology of MDD in this relatively large study using optimal imaging acquisition and analysis; however, this does not eliminate the possibility that certain patient subgroups show WM disruption associated with depression.

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Voxel-based detection of white matter abnormalities in mild Alzheimer disease

Abstract: Voxel-wise comparison of whole-brain anisotropy revealed widely distributed disintegration of white matter in mild Alzheimer disease (AD). The white matter shows a different pattern of degeneration from gray matter and may be an independent factor in the progress of AD.

Cited by 195 publications

References 30 publications

Relationships between Hippocampal Atrophy, White Matter Disruption, and Gray Matter Hypometabolism in Alzheimer's Disease

Relationships between Hippocampal Atrophy, White Matter Disruption, and Gray Matter Hypometabolism in Alzheimer's Disease

In Vivo Structural Neuroanatomy of Corpus Callosum in Alzheimer's Disease and Mild Cognitive Impairment Using Different MRI Techniques: A Review

Reconciling Variable Findings of White Matter Integrity in Major Depressive Disorder

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