Progression of Corpus Callosum Atrophy in Alzheimer Disease

Teipel, Stefan J.; Bayer, Wolfram; Alexander, Gene E.; Zebuhr, Y; Teichberg, Diane; Kulic, Luka; Schapiro, M. B.; Möller, Hans; Rapoport, Stanley I.; Hampel, Harald

doi:10.1001/archneur.59.2.243

Cited by 174 publications

(138 citation statements)

References 25 publications

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“…Our findings are consistent with previous reports of regionally specific posterior callosal atrophy in mild AD [23,38]. Studies showing more pervasive callosal atrophy have typically involved AD patients with moderate or severe dementia [18,20,21,23,27,34,35]. For example, one study [23] found atrophy in all callosal subregions in their total AD sample; however, when just the mild AD subset from the AD group was analyzed, only the posterior mid-body, isthmus, and splenium showed significant reduction relative to controls.…”

Section: Discussionsupporting

confidence: 91%

“…Also, longitudinal research involving the early AD, MCI, and CC groups will help determine the onset and progression of these callosal changes. One study [34] found that the annual rate of atrophy of the total corpus callosum, rostrum, anterior truncus, and splenium of AD patients was 7.7%, 12.1%, 10.3% and 7.3%, respectively. An additional important future direction will be the application of computational anatomic approaches to model shape changes in the early preclinical stages of AD and in those at risk for AD.…”

Section: Discussionmentioning

confidence: 99%

“…In patients with AD, neurofibrillary changes are first seen in the entorhinal region and then progress to other closely related medial temporal areas including the hippocampus [5,6]. Previous magnetic resonance imaging (MRI) studies have shown the corpus callosum is also a structure susceptible to atrophy in AD [12,18,20,21,23,27,34,35,38]. Although the results in AD have been variable regarding which subregions of the corpus callosum are affected, all of these studies except one [12] have found significant atrophy in at least the posterior region.…”

Section: Introductionmentioning

confidence: 99%

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Regionally specific atrophy of the corpus callosum in AD, MCI and cognitive complaints

Wang

Saykin

Flashman

et al. 2006

Neurobiology of Aging

102

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The goal of the present study was to determine if there are global or regionally specific decreases in callosal area in early Alzheimer's disease (AD) and mild cognitive impairment (MCI). In addition, this study examined the corpus callosum of healthy older adults who have subjective cognitive complaints (CC) but perform within normal limits on neuropsychological tests. We used a semi-automated procedure to examine the total and regional areas of the corpus callosum in 22 patients with early AD, 28 patients with amnestic MCI, 28 healthy older adults with cognitive complaints, and 50 demographically matched healthy controls (HC). The AD, MCI, and CC groups all showed a significant reduction of the posterior region (isthmus and splenium) relative to healthy controls. The AD group also had a significantly smaller overall callosum than the controls. The demonstration of callosal atrophy in older adults with cognitive complaints suggests that callosal changes occur very early in the dementing process, and that these earliest changes may be too subtle for detection by neuropsychological assessments, including memory tests.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regionally specific atrophy of the corpus callosum in AD, MCI and cognitive complaints

Wang

Saykin

Flashman

et al. 2006

Neurobiology of Aging

102

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“…Relation of the atrophic change to the pathologic involvement, however, needs to be demonstrated with postmortem studies. 87 Automated or semiautomated MR volumetry techniques that are less labor-intensive than tracing specific regions of interest are being used to track the structural changes that take place within the brain during the progression of AD. One of the most promising techniques used for this purpose is the brain boundary shift integral (BBSI) developed by Fox and Freeborough.…”

Section: Both Antemortem and Postmortem Mr Studies Indicate That Mr-bmentioning

confidence: 99%

Quantitative magnetic resonance techniques as surrogate markers of Alzheimer’s disease

Kantarci

Jack

2004

Neurotherapeutics

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Summary: Recent advances in understanding the molecular biology of Alzheimer's disease (AD) offer the promise of useful therapeutic intervention in the foreseeable future. Hence, improved methods for early diagnosis and noninvasive surrogates of disease severity in AD have become more imperative. Various quantitative magnetic resonance (MR) techniques that measure the anatomic, biochemical, microstructural, functional, and blood-flow changes are being evaluated as possible surrogate measures of disease progression. Cross-sectional and longitudinal studies indicate that MR-based volume measurements are potential surrogates of disease progression in AD, starting from the preclinical stages. The validity of MR-based volumetry as a surrogate marker for therapeutic efficacy in AD remains to be tested in a positive disease-modifying drug trial. Recent development of amyloid imaging tracers for positron emission tomography has been a major breakthrough in the field of imaging markers for AD. Efforts to image plaques are also underway in MR imaging. As with indirect MR measures, these approaches of directly imaging the pathological substrate will need to undergo a validation process with longitudinal studies to prove their usefulness as surrogate markers in AD.

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“…One of the proposed targets is the corpus callosum (CC), a large white matter tract that includes the neural pathway starting at the nucleus basalis of Meynert, and connects the majority of frontal, parietal, and occipital cortical areas to corresponding regions in the contralateral hemisphere. CC size changes and atrophy occur in AD patients and correlate with progression of dementia severity 9, 10, 11. This, coupled with the fact that stem cells migrate through large white matter tracts,12, 13, 14 makes the CC a potentially effective target.…”

Section: Introductionmentioning

confidence: 99%

Human neural stem cell transplantation into the corpus callosum of Alzheimer's mice

McGinley

Kashlan

Chen

et al. 2017

Ann Clin Transl Neurol

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The hippocampus has been the target of stem cell transplantations in preclinical studies focused on Alzheimer's disease, with results showing improvements in histological and behavioral outcomes. The corpus callosum is another structure that is affected early in Alzheimer's disease. Therefore, we hypothesize that this structure is a novel target for human neural stem cell transplantation in transgenic Alzheimer's disease mouse models. This study demonstrates the feasibility of targeting the corpus callosum and identifies an effective immunosuppression regimen for transplanted neural stem cell survival. These results support further preclinical development of the corpus callosum as a therapeutic target in Alzheimer's disease.

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Progression of Corpus Callosum Atrophy in Alzheimer Disease

Abstract: Measurement of corpus callosum size allows in vivo mapping of neocortical neurodegeneration in AD over a wide range of clinical dementia severities and may be used as a surrogate marker for evaluation of drug efficacy.

Cited by 174 publications

References 25 publications

Regionally specific atrophy of the corpus callosum in AD, MCI and cognitive complaints

Regionally specific atrophy of the corpus callosum in AD, MCI and cognitive complaints

Quantitative magnetic resonance techniques as surrogate markers of Alzheimer’s disease

Human neural stem cell transplantation into the corpus callosum of Alzheimer's mice

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