Alzheimer disease: Postmortem neuropathologic correlates of antemortem 1H MR spectroscopy metabolite measurements

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Abstract

Purpose: To determine the neuropathologic correlates of antemortem hydrogen 1 (1H) magnetic resonance (MR) spectroscopy metabolite measurements in subjects with Alzheimer disease (AD)-type pathology. Materials and Methods: This study was approved by the institutional review board and was compliant with HIPAA regulations. Informed consent was obtained from each subject. The authors identified 54 subjects who underwent antemortem 1H MR spectroscopy and were clinically healthy or had AD-type pathology with low to high likelihood of AD according to National Institute on Aging-Reagan neuropathologic criteria at autopsy. They investigated the associations between 1H MR spectroscopy metabolite measurements and Braak neurofibrillary tangle stage (Braak stage), neuritic plaque score, and AD likelihood, with adjustments for subject age, subject sex, and time between 1H MR spectroscopy and death. Results: Decreases in N-acetylaspartate-to-creatine ratio, an index of neuronal integrity, and increases in myo-inositol-to-creatine ratio were associated with higher Braak stage, higher neuritic plaque score, and greater likelihood of AD. The N-acetylaspartate-to-myo-inositol ratio proved to be the strongest predictor of the pathologic likelihood of AD. The strongest association observed was that between N-acetylaspartate-to-myo-inositol ratio and Braak stage (RN 2 = 0.47, P < .001). Conclusion: Antemortem 1H MR spectroscopy metabolite changes correlated with AD-type pathology seen at autopsy. The study findings validated 1H MR spectroscopy metabolite measurements against the neuropathologic criteria for AD, and when combined with prior longitudinal 1H MR spectroscopy findings, indicate that these measurements could be used as biomarkers for disease progression in clinical trials.

Original languageEnglish (US)
Pages (from-to)210-220
Number of pages11
JournalRadiology
Volume248
Issue number1
DOIs
StatePublished - Jul 2008

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Alzheimer Disease
Magnetic Resonance Spectroscopy
Neurofibrillary Tangles
Inositol
Creatine
Amyloid Plaques
Pathology
Autopsy
National Institute on Aging (U.S.)
Health Insurance Portability and Accountability Act
Research Ethics Committees
Informed Consent
Disease Progression
Hydrogen
Biomarkers
Clinical Trials
N-acetylaspartate

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

Cite this

@article{75ced7702c0b4a2a949f52e0f7a946b3,
title = "Alzheimer disease: Postmortem neuropathologic correlates of antemortem 1H MR spectroscopy metabolite measurements",
abstract = "Purpose: To determine the neuropathologic correlates of antemortem hydrogen 1 (1H) magnetic resonance (MR) spectroscopy metabolite measurements in subjects with Alzheimer disease (AD)-type pathology. Materials and Methods: This study was approved by the institutional review board and was compliant with HIPAA regulations. Informed consent was obtained from each subject. The authors identified 54 subjects who underwent antemortem 1H MR spectroscopy and were clinically healthy or had AD-type pathology with low to high likelihood of AD according to National Institute on Aging-Reagan neuropathologic criteria at autopsy. They investigated the associations between 1H MR spectroscopy metabolite measurements and Braak neurofibrillary tangle stage (Braak stage), neuritic plaque score, and AD likelihood, with adjustments for subject age, subject sex, and time between 1H MR spectroscopy and death. Results: Decreases in N-acetylaspartate-to-creatine ratio, an index of neuronal integrity, and increases in myo-inositol-to-creatine ratio were associated with higher Braak stage, higher neuritic plaque score, and greater likelihood of AD. The N-acetylaspartate-to-myo-inositol ratio proved to be the strongest predictor of the pathologic likelihood of AD. The strongest association observed was that between N-acetylaspartate-to-myo-inositol ratio and Braak stage (RN 2 = 0.47, P < .001). Conclusion: Antemortem 1H MR spectroscopy metabolite changes correlated with AD-type pathology seen at autopsy. The study findings validated 1H MR spectroscopy metabolite measurements against the neuropathologic criteria for AD, and when combined with prior longitudinal 1H MR spectroscopy findings, indicate that these measurements could be used as biomarkers for disease progression in clinical trials.",
author = "Kantarci, {Kejal M} and Knopman, {David S} and Dickson, {Dennis W} and Parisi, {Joseph E} and Whitwell, {Jennifer Lynn} and Weigand, {Stephen D.} and Josephs, {Keith Anthony} and Boeve, {Bradley F} and Petersen, {Ronald Carl} and Jack, {Clifford R Jr.}",
year = "2008",
month = "7",
doi = "10.1148/radiol.2481071590",
language = "English (US)",
volume = "248",
pages = "210--220",
journal = "Radiology",
issn = "0033-8419",
publisher = "Radiological Society of North America Inc.",
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TY - JOUR

T1 - Alzheimer disease

T2 - Postmortem neuropathologic correlates of antemortem 1H MR spectroscopy metabolite measurements

AU - Kantarci, Kejal M

AU - Knopman, David S

AU - Dickson, Dennis W

AU - Parisi, Joseph E

AU - Whitwell, Jennifer Lynn

AU - Weigand, Stephen D.

AU - Josephs, Keith Anthony

AU - Boeve, Bradley F

AU - Petersen, Ronald Carl

AU - Jack, Clifford R Jr.

PY - 2008/7

Y1 - 2008/7

N2 - Purpose: To determine the neuropathologic correlates of antemortem hydrogen 1 (1H) magnetic resonance (MR) spectroscopy metabolite measurements in subjects with Alzheimer disease (AD)-type pathology. Materials and Methods: This study was approved by the institutional review board and was compliant with HIPAA regulations. Informed consent was obtained from each subject. The authors identified 54 subjects who underwent antemortem 1H MR spectroscopy and were clinically healthy or had AD-type pathology with low to high likelihood of AD according to National Institute on Aging-Reagan neuropathologic criteria at autopsy. They investigated the associations between 1H MR spectroscopy metabolite measurements and Braak neurofibrillary tangle stage (Braak stage), neuritic plaque score, and AD likelihood, with adjustments for subject age, subject sex, and time between 1H MR spectroscopy and death. Results: Decreases in N-acetylaspartate-to-creatine ratio, an index of neuronal integrity, and increases in myo-inositol-to-creatine ratio were associated with higher Braak stage, higher neuritic plaque score, and greater likelihood of AD. The N-acetylaspartate-to-myo-inositol ratio proved to be the strongest predictor of the pathologic likelihood of AD. The strongest association observed was that between N-acetylaspartate-to-myo-inositol ratio and Braak stage (RN 2 = 0.47, P < .001). Conclusion: Antemortem 1H MR spectroscopy metabolite changes correlated with AD-type pathology seen at autopsy. The study findings validated 1H MR spectroscopy metabolite measurements against the neuropathologic criteria for AD, and when combined with prior longitudinal 1H MR spectroscopy findings, indicate that these measurements could be used as biomarkers for disease progression in clinical trials.

AB - Purpose: To determine the neuropathologic correlates of antemortem hydrogen 1 (1H) magnetic resonance (MR) spectroscopy metabolite measurements in subjects with Alzheimer disease (AD)-type pathology. Materials and Methods: This study was approved by the institutional review board and was compliant with HIPAA regulations. Informed consent was obtained from each subject. The authors identified 54 subjects who underwent antemortem 1H MR spectroscopy and were clinically healthy or had AD-type pathology with low to high likelihood of AD according to National Institute on Aging-Reagan neuropathologic criteria at autopsy. They investigated the associations between 1H MR spectroscopy metabolite measurements and Braak neurofibrillary tangle stage (Braak stage), neuritic plaque score, and AD likelihood, with adjustments for subject age, subject sex, and time between 1H MR spectroscopy and death. Results: Decreases in N-acetylaspartate-to-creatine ratio, an index of neuronal integrity, and increases in myo-inositol-to-creatine ratio were associated with higher Braak stage, higher neuritic plaque score, and greater likelihood of AD. The N-acetylaspartate-to-myo-inositol ratio proved to be the strongest predictor of the pathologic likelihood of AD. The strongest association observed was that between N-acetylaspartate-to-myo-inositol ratio and Braak stage (RN 2 = 0.47, P < .001). Conclusion: Antemortem 1H MR spectroscopy metabolite changes correlated with AD-type pathology seen at autopsy. The study findings validated 1H MR spectroscopy metabolite measurements against the neuropathologic criteria for AD, and when combined with prior longitudinal 1H MR spectroscopy findings, indicate that these measurements could be used as biomarkers for disease progression in clinical trials.

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U2 - 10.1148/radiol.2481071590

DO - 10.1148/radiol.2481071590

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