In vivo imaging of region and cell type specific neocortical neurodegeneration in Alzheimer's disease

Perspectives of MRI derived corpus callosum measurement for mapping disease progression and effects of therapy. Evidence from studies with MRI, EEG and PET

H. Hampel, S. J. Teipel, Gene E Alexander, O. Pogarell, S. I. Rapoport, H. J. Möller

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74 Citations (Scopus)

Abstract

Neuropathological studies in Alzheimer's disease (AD) indicate specific loss of layer III and V large pyramidal neurons in association cortex. These neurons give rise to long cortico-cortical connections, projecting through the corpus callosum, in an anterior-posterior topology. Based on these findings we hypothesized that regional corpus callosum atrophy may be a potential in vivo marker for neocortical neuronal loss in AD. To evaluate this hypothesis, we developed a method to measure cross-sectional area of the corpus callosum and of five corpus callosum subregions on midsagittal magnetic resonance imaging scans (MRI). In a subsequent series of six experimental studies using MRI, 18FDG-PET and EEG, we investigated the relation of white matter hyperintensities (WMH) to corpus callosum size and correlated regional pattern of corpus callosum atrophy with regional cortical metabolic decline as well as intracortical coherencies. Mean total corpus callosum area was reduced significantly in AD patients compared to healthy age-matched controls, with the greatest changes in the rostrum and the splenium and relative sparing of the truncus. The regional pattern of corpus callosum atrophy was independent of WMH load and correlated significantly with pattern of regional metabolic decline measured with 18FDG-PET, the degree of cognitive impairment and regional decline of bilateral intracortical-coherency in EEG in AD patients. We further found that hippocampus atrophy, as a marker of early allocortical degeneration, was more pronounced than total corpus callosum atrophy in mild stages of AD. Regional corpus callosum atrophy in mild disease, however, suggested early neocortical degeneration in AD. In a longitudinal study, AD patients showed significantly greater rates of corpus callosum atrophy than controls. Rates of atrophy correlated with progression of clinical dementia severity in AD. Our results indicate that regional corpus callosum atrophy in AD patients represents the loss of callosal efferent neurons in corresponding regions of the neocortex. As these neurons are a subset of cortico-cortical projecting neurons, region-specific corpus callosum atrophy may serve as a marker of progressive neocortical disconnection in AD. In combination with measurement of hippocampal atrophy, assessment of corpus callosum atrophy over time in individual patients is useful to evaluate effects on brain structure of currently developed drugs, thought to slow or modify AD progression.

Original languageEnglish (US)
Pages (from-to)837-855
Number of pages19
JournalJournal of Neural Transmission
Volume109
Issue number5-6
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Corpus Callosum
Positron-Emission Tomography
Disease Progression
Electroencephalography
Alzheimer Disease
Magnetic Resonance Imaging
Atrophy
Therapeutics
Fluorodeoxyglucose F18
Neurons
Efferent Neurons
Pyramidal Cells
Neocortex
Longitudinal Studies
Dementia

Keywords

  • Alzheimer's disease
  • Brain atrophy
  • Corpus callosum
  • Dementia
  • EEG
  • Hippocampus
  • Mild cognitive impairment
  • MRI
  • Neocortex
  • Neurodegeneration
  • Neuroimaging
  • PET
  • Prevention
  • Progression
  • Therapy

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "In vivo imaging of region and cell type specific neocortical neurodegeneration in Alzheimer's disease: Perspectives of MRI derived corpus callosum measurement for mapping disease progression and effects of therapy. Evidence from studies with MRI, EEG and PET",
abstract = "Neuropathological studies in Alzheimer's disease (AD) indicate specific loss of layer III and V large pyramidal neurons in association cortex. These neurons give rise to long cortico-cortical connections, projecting through the corpus callosum, in an anterior-posterior topology. Based on these findings we hypothesized that regional corpus callosum atrophy may be a potential in vivo marker for neocortical neuronal loss in AD. To evaluate this hypothesis, we developed a method to measure cross-sectional area of the corpus callosum and of five corpus callosum subregions on midsagittal magnetic resonance imaging scans (MRI). In a subsequent series of six experimental studies using MRI, 18FDG-PET and EEG, we investigated the relation of white matter hyperintensities (WMH) to corpus callosum size and correlated regional pattern of corpus callosum atrophy with regional cortical metabolic decline as well as intracortical coherencies. Mean total corpus callosum area was reduced significantly in AD patients compared to healthy age-matched controls, with the greatest changes in the rostrum and the splenium and relative sparing of the truncus. The regional pattern of corpus callosum atrophy was independent of WMH load and correlated significantly with pattern of regional metabolic decline measured with 18FDG-PET, the degree of cognitive impairment and regional decline of bilateral intracortical-coherency in EEG in AD patients. We further found that hippocampus atrophy, as a marker of early allocortical degeneration, was more pronounced than total corpus callosum atrophy in mild stages of AD. Regional corpus callosum atrophy in mild disease, however, suggested early neocortical degeneration in AD. In a longitudinal study, AD patients showed significantly greater rates of corpus callosum atrophy than controls. Rates of atrophy correlated with progression of clinical dementia severity in AD. Our results indicate that regional corpus callosum atrophy in AD patients represents the loss of callosal efferent neurons in corresponding regions of the neocortex. As these neurons are a subset of cortico-cortical projecting neurons, region-specific corpus callosum atrophy may serve as a marker of progressive neocortical disconnection in AD. In combination with measurement of hippocampal atrophy, assessment of corpus callosum atrophy over time in individual patients is useful to evaluate effects on brain structure of currently developed drugs, thought to slow or modify AD progression.",
keywords = "Alzheimer's disease, Brain atrophy, Corpus callosum, Dementia, EEG, Hippocampus, Mild cognitive impairment, MRI, Neocortex, Neurodegeneration, Neuroimaging, PET, Prevention, Progression, Therapy",
author = "H. Hampel and Teipel, {S. J.} and Alexander, {Gene E} and O. Pogarell and Rapoport, {S. I.} and M{\"o}ller, {H. J.}",
year = "2002",
doi = "10.1007/s007020200069",
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pages = "837--855",
journal = "Journal of Neural Transmission",
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TY - JOUR

T1 - In vivo imaging of region and cell type specific neocortical neurodegeneration in Alzheimer's disease

T2 - Perspectives of MRI derived corpus callosum measurement for mapping disease progression and effects of therapy. Evidence from studies with MRI, EEG and PET

AU - Hampel, H.

AU - Teipel, S. J.

AU - Alexander, Gene E

AU - Pogarell, O.

AU - Rapoport, S. I.

AU - Möller, H. J.

PY - 2002

Y1 - 2002

N2 - Neuropathological studies in Alzheimer's disease (AD) indicate specific loss of layer III and V large pyramidal neurons in association cortex. These neurons give rise to long cortico-cortical connections, projecting through the corpus callosum, in an anterior-posterior topology. Based on these findings we hypothesized that regional corpus callosum atrophy may be a potential in vivo marker for neocortical neuronal loss in AD. To evaluate this hypothesis, we developed a method to measure cross-sectional area of the corpus callosum and of five corpus callosum subregions on midsagittal magnetic resonance imaging scans (MRI). In a subsequent series of six experimental studies using MRI, 18FDG-PET and EEG, we investigated the relation of white matter hyperintensities (WMH) to corpus callosum size and correlated regional pattern of corpus callosum atrophy with regional cortical metabolic decline as well as intracortical coherencies. Mean total corpus callosum area was reduced significantly in AD patients compared to healthy age-matched controls, with the greatest changes in the rostrum and the splenium and relative sparing of the truncus. The regional pattern of corpus callosum atrophy was independent of WMH load and correlated significantly with pattern of regional metabolic decline measured with 18FDG-PET, the degree of cognitive impairment and regional decline of bilateral intracortical-coherency in EEG in AD patients. We further found that hippocampus atrophy, as a marker of early allocortical degeneration, was more pronounced than total corpus callosum atrophy in mild stages of AD. Regional corpus callosum atrophy in mild disease, however, suggested early neocortical degeneration in AD. In a longitudinal study, AD patients showed significantly greater rates of corpus callosum atrophy than controls. Rates of atrophy correlated with progression of clinical dementia severity in AD. Our results indicate that regional corpus callosum atrophy in AD patients represents the loss of callosal efferent neurons in corresponding regions of the neocortex. As these neurons are a subset of cortico-cortical projecting neurons, region-specific corpus callosum atrophy may serve as a marker of progressive neocortical disconnection in AD. In combination with measurement of hippocampal atrophy, assessment of corpus callosum atrophy over time in individual patients is useful to evaluate effects on brain structure of currently developed drugs, thought to slow or modify AD progression.

AB - Neuropathological studies in Alzheimer's disease (AD) indicate specific loss of layer III and V large pyramidal neurons in association cortex. These neurons give rise to long cortico-cortical connections, projecting through the corpus callosum, in an anterior-posterior topology. Based on these findings we hypothesized that regional corpus callosum atrophy may be a potential in vivo marker for neocortical neuronal loss in AD. To evaluate this hypothesis, we developed a method to measure cross-sectional area of the corpus callosum and of five corpus callosum subregions on midsagittal magnetic resonance imaging scans (MRI). In a subsequent series of six experimental studies using MRI, 18FDG-PET and EEG, we investigated the relation of white matter hyperintensities (WMH) to corpus callosum size and correlated regional pattern of corpus callosum atrophy with regional cortical metabolic decline as well as intracortical coherencies. Mean total corpus callosum area was reduced significantly in AD patients compared to healthy age-matched controls, with the greatest changes in the rostrum and the splenium and relative sparing of the truncus. The regional pattern of corpus callosum atrophy was independent of WMH load and correlated significantly with pattern of regional metabolic decline measured with 18FDG-PET, the degree of cognitive impairment and regional decline of bilateral intracortical-coherency in EEG in AD patients. We further found that hippocampus atrophy, as a marker of early allocortical degeneration, was more pronounced than total corpus callosum atrophy in mild stages of AD. Regional corpus callosum atrophy in mild disease, however, suggested early neocortical degeneration in AD. In a longitudinal study, AD patients showed significantly greater rates of corpus callosum atrophy than controls. Rates of atrophy correlated with progression of clinical dementia severity in AD. Our results indicate that regional corpus callosum atrophy in AD patients represents the loss of callosal efferent neurons in corresponding regions of the neocortex. As these neurons are a subset of cortico-cortical projecting neurons, region-specific corpus callosum atrophy may serve as a marker of progressive neocortical disconnection in AD. In combination with measurement of hippocampal atrophy, assessment of corpus callosum atrophy over time in individual patients is useful to evaluate effects on brain structure of currently developed drugs, thought to slow or modify AD progression.

KW - Alzheimer's disease

KW - Brain atrophy

KW - Corpus callosum

KW - Dementia

KW - EEG

KW - Hippocampus

KW - Mild cognitive impairment

KW - MRI

KW - Neocortex

KW - Neurodegeneration

KW - Neuroimaging

KW - PET

KW - Prevention

KW - Progression

KW - Therapy

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U2 - 10.1007/s007020200069

DO - 10.1007/s007020200069

M3 - Article

VL - 109

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EP - 855

JO - Journal of Neural Transmission

JF - Journal of Neural Transmission

SN - 0300-9564

IS - 5-6

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