Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-586b7cd67f-tf8b9 Total loading time: 0 Render date: 2024-11-22T20:44:16.851Z Has data issue: false hasContentIssue false

25 - Molecular imaging of Alzheimer's disease

from Section IV - Cognitive Disorders

Published online by Cambridge University Press:  10 January 2011

By
Norbert Schuff
Edited by
Martha E. Shenton  and
Bruce I. Turetsky
Norbert Schuff
Affiliation:
Center for Imaging of Neurodegenerative Diseases at the Veterans Affairs Medical Center and Department of Radiology and Biomedical Imaging University of California San Francisco San Francisco, CA, USA
Martha E. Shenton
Affiliation:
VA Boston Healthcare System and Brigham and Women's Hospital, Harvard Medical School
Bruce I. Turetsky
Affiliation:
University of Pennsylvania
Get access

Summary

Abstract

Neurochemical imaging offers an opportunity to study at a molecular level in-vivo the neuronal substrates that underpin Alzheimer's disease (AD) and related disorders, such as mild cognitive impairment (MCI). In particular, proton magnetic resonance spectroscopic imaging (1H MRSI) is unique among diagnostic imaging modalities because the method can measure several different brain metabolites simultaneously, including N-acetylaspartate (NAA), a neuronal integrity marker, and myo-inositol (MI), a potential glial marker. The goal of this chapter is to review key findings of 1H MRSI in AD, MCI and aging, and to discuss the potential value of this technology for diagnosis and prognosis of AD as well as for the assessment of therapeutic intervention. Other neurochemical imaging technologies such as direct mapping of neurotransmitter systems using emission tomography (PET) tracers and new trends, such as amyloid PET imaging are also briefly discussed.

Introduction

Alzheimer's disease (AD) is the most common cause of dementia and a growing health problem globally, affecting 20% of the population over 80 years of age (Ferri et al., 2005). Currently, the definite diagnosis of AD can only be made through autopsy to find the pathological hallmarks of the disease: microscopic amyloid plaques and neurofibrillary tangles. Macroscopically, AD is characterized by progressive loss of brain tissue that leads to a rapid decline in cognitive function.

Keywords

1H MRSIAlzheimer's diseaseamyloid PET imagingpositron emission tomographyneurotransmitter systemsneurochemical imaging modalitiesmild cognitive impairmentmolecular imaging
Type
Chapter
Information
Understanding Neuropsychiatric Disorders
Insights from Neuroimaging
 , pp. 351 - 360
Publisher: Cambridge University Press
Print publication year: 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Ackl, N, Ising, M, Schreiber, Y A, Atiya, M, Sonntag, A and Auer, D P. 2005. Hippocampal metabolic abnormalities in mild cognitive impairment and Alzheimer's disease. Neurosci Lett 384, 23–8.Google Scholar
Adalsteinsson, E, Sullivan, E V, Kleinhans, N, Spielman, D M and Pfefferbaum, A. 2000. Longitudinal decline of the neuronal marker N-acetyl aspartate in Alzheimer's disease. Lancet 355, 1696–7.Google Scholar
Birken, D L and Oldendorf, W H. 1989. N-acetyl-L-aspartic acid: A literature review of a compound prominent in 1H-NMR spectroscopic studies of brain. Neurosci Biobehav Rev 13, 23–31.Google Scholar
Bitsch, A, Bruhn, H, Vougioukas, V, et al. 1999. Inflammatory CNS demyelination: Histopathologic correlation with in vivo quantitative proton MR spectroscopy. Am J Neuroradiol 20, 1619–27.Google Scholar
Blakely, R D and Coyle, J T. 1988. The neurobiology of N-acetylaspartylglutamate. Int Rev Neurobiol 30, 39–100.Google Scholar
Braak, H and Braak, E. 1998. Evolution of neuronal changes in the course of Alzheimer's disease. J Neural Transm Suppl 53, 127–40.Google Scholar
Brand, A, Richter-Landsberg, C and Leibfritz, D. 1993. Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev Neurosci 15, 289–98.Google Scholar
Capizzano, A A, Schuff, N, Amend, D L, et al. 2000. Subcortical ischemic vascular dementia: Assessment with quantitative MR imaging and 1H MR spectroscopy. Am J Neuroradiol 21, 621–30.Google Scholar
Catani, M, Cherubini, A, Howard, R, et al. 2001. (1)H-MR spectroscopy differentiates mild cognitive impairment from normal brain aging. Neuroreport 12, 2315–7.Google Scholar
Chantal, S, Braun, C M, Bouchard, R W, Labelle, M and Boulanger, Y. 2004. Similar 1H magnetic resonance spectroscopic metabolic pattern in the medial temporal lobes of patients with mild cognitive impairment and Alzheimer disease. Brain Res 1003, 26–35.CrossRefGoogle Scholar
Chao, L L, Mueller, S G, Buckley, S T, et al. 2010. Evidence of neurodegeneration in brains of older adults who do not yet fulfill MCI criteria. Neurobiol Aging 31, 368–77.Google Scholar
Chao, L L, Schuff, N, Kramer, J H, et al. 2005. Reduced medial temporal lobe N-acetylaspartate in cognitively impaired but nondemented patients. Neurology 64, 282–9.Google Scholar
Dixon, R M, Bradley, K M, Budge, M M, Styles, P and Smith, A D. 2002. Longitudinal quantitative proton magnetic resonance spectroscopy of the hippocampus in Alzheimer's disease. Brain 125, 2332–41.Google Scholar
Engelborghs, S and Deyn, P P. 1997. The neurochemistry of Alzheimer's disease. Acta Neurol Belg 97, 67–84.Google Scholar
Ernst, T, Chang, L, Melchor, R and Mehringer, C M. 1997. Frontotemporal dementia and early Alzheimer disease: Differentiation with frontal lobe H-1 MR spectroscopy. Radiology 203, 829–36.CrossRefGoogle Scholar
Fernandez, A, Garcia-Segura, J M, Ortiz, T, et al. 2005. Proton magnetic resonance spectroscopy and magnetoencephalographic estimation of delta dipole density: A combination of techniques that may contribute to the diagnosis of Alzheimer's disease. Dement Geriatr Cogn Disord 20, 169–77.CrossRefGoogle Scholar
Ferri, C P, Prince, M, Brayne, C, et al. 2005. Global prevalence of dementia: A Delphi consensus study. Lancet 366, 2112–7.Google Scholar
Forsberg, A, Engler, H, Almkvist, O, et al. 2008. PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiol Aging 29, 1456–65.Google Scholar
Glanville, N T, Byers, D M, Cook, H W, Spence, M W and Palmer, F B. 1989. Differences in the metabolism of inositol and phosphoinositides by cultured cells of neuronal and glial origin. Biochim Biophys Acta 1004, 169–79.Google Scholar
Glodzik, L, King, K G, Gonen, O, Liu, S, Santi, S and Leon, M J. 2008. Memantine decreases hippocampal glutamate levels: A magnetic resonance spectroscopy study. Prog Neuropsychopharmacol Biol Psychiatry 32, 1005–12.Google Scholar
Guimaraes, A R, Schwartz, P, Prakash, M R, et al. 1995. Quantitative in vivo 1H nuclear magnetic resonance spectroscopic imaging of neuronal loss in rat brain. Neuroscience 69, 1095–101.Google Scholar
Jessen, F, Block, W, Traber, F, et al. 2001. Decrease of N-acetylaspartate in the MTL correlates with cognitive decline of AD patients. Neurology 57, 930–2.Google Scholar
Kadir, A, Almkvist, O, Wall, A, Langstrom, B and Nordberg, A. 2006. PET imaging of cortical 11C-nicotine binding correlates with the cognitive function of attention in Alzheimer's disease. Psychopharmacology (Berl) 188, 509–20.Google Scholar
Kaiser, L G, Young, K, Meyerhoff, D J, Mueller, S G and Matson, G B. 2008. A detailed analysis of localized J-difference GABA editing: theoretical and experimental study at 4 T. NMR Biomed 21, 22–32.Google Scholar
Kantarci, K, Jack, C R, Xu, Y C, Campeau, N G, O'Brien, P C, Smith, G E, et al. 2000. Regional metabolic patterns in mild cognitive impairment and Alzheimer's disease: A 1H MRS study. Neurology 2000; 55: 210–7.Google Scholar
Kantarci, K, Knopman, D S, Dickson, D W, et al. 2008. Alzheimer disease: Postmortem neuropathologic correlates of antemortem 1H MR spectroscopy metabolite measurements. Radiology 248, 210–20.Google Scholar
Kantarci, K, Smith, G E, Ivnik, R J, et al. 2002. 1H magnetic resonance spectroscopy, cognitive function, and apolipoprotein E genotype in normal aging, mild cognitive impairment and Alzheimer's disease. J Int Neuropsychol Soc 8, 934–42.Google Scholar
Kantarci, K, Weigand, S D, Petersen, R C, et al. 2007. Longitudinal 1H MRS changes in mild cognitive impairment and Alzheimer's disease. Neurobiol Aging 28, 1330–9.Google Scholar
Kemppainen, N M, Aalto, S, Wilson, I A, et al. 2007. PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment. Neurology 68, 1603–06.Google Scholar
Kepe, V, Barrio, J R, Huang, S C, et al. 2006. Serotonin 1A receptors in the living brain of Alzheimer's disease patients. Proc Natl Acad Sci USA 103, 702–07.Google Scholar
Klein, J. 2000. Membrane breakdown in acute and chronic neurodegeneration: Focus on choline-containing phospholipids. J Neural Transm 107, 1027–63.Google Scholar
Klunk, W E, Panchalingam, K, Moossy, J, McClure, R J and Pettegrew, J W. 1992. N-acetyl-L-aspartate and other amino acid metabolites in Alzheimer's disease brain: A preliminary proton nuclear magnetic resonance study. Neurology 42, 1578–85.Google Scholar
Koller, K J, Zaczek, R and Coyle, J T. 1984. N-acetyl-aspartyl-glutamate: Regional levels in rat brain and the effects of brain lesions as determined by a new HPLC method. J Neurochem 43, 1136–42.Google Scholar
Krishnan, K R, Charles, H C, Doraiswamy, P M, et al. 2003. Randomized, placebo-controlled trial of the effects of donepezil on neuronal markers and hippocampal volumes in Alzheimer's disease. Am J Psychiatry 160, 2003–11.Google Scholar
Kuhl, D E, Koeppe, R A, Minoshima, S, et al. 1999. In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer's disease. Neurology 52, 691–9.Google Scholar
Lin, A P, Shic, F, Enriquez, C and Ross, B D. 2003. Reduced glutamate neurotransmission in patients with Alzheimer's disease – an in vivo (13)C magnetic resonance spectroscopy study. Magma 16, 29–42.Google Scholar
Metastasio, A, Rinaldi, P, Tarducci, R, et al. 2006. Conversion of MCI to dementia: Role of proton magnetic resonance spectroscopy. Neurobiol Aging 27, 926–32.Google Scholar
Meyerhoff, D J, MacKay, S, Constans, J M, et al. 1994. Axonal injury and membrane alterations in Alzheimer's disease suggested by in vivo proton magnetic resonance spectroscopic imaging. Ann Neurol 36, 40–7.Google Scholar
Mihara, M, Hattori, N, Abe, K, Sakoda, S and Sawada, T. 2006. Magnetic resonance spectroscopic study of Alzheimer's disease and frontotemporal dementia/Pick complex. Neuroreport 17, 413–6.Google Scholar
Moats, R A, Ernst, T, Shonk, T K and Ross, B D. 1994. Abnormal cerebral metabolite concentrations in patients with probable Alzheimer disease. Magn Reson Med 32, 110–5.Google Scholar
Nordberg, A. 1993. Clinical studies in Alzheimer patients with positron emission tomography. Behav Brain Res 57, 215–24.Google Scholar
Nordberg, A, Hartvig, P, Lilja, A, et al. 1990. Decreased uptake and binding of 11C-nicotine in brain of Alzheimer patients as visualized by positron emission tomography. J Neural Transm Park Dis Dement Sect 2, 215–24.Google Scholar
Nordberg, A, Lundqvist, H, Hartvig, P, Lilja, A and Langstrom, B. 1995. Kinetic analysis of regional (S)(–)11C-nicotine binding in normal and Alzheimer brains – In vivo assessment using positron emission tomography. Alzheimer Dis Assoc Disord 9, 21–7.Google Scholar
Olson, B L, Holshouser, B A, Britt, W, et al. 2008. Longitudinal metabolic and cognitive changes in mild cognitive impairment patients. Alzheimer Dis Assoc Disord 22, 269–77.Google Scholar
Panza, F, D'Introno, A, Colacicco, A M, et al. 2005. Current epidemiology of mild cognitive impairment and other predementia syndromes. Am J Geriatr Psychiatry 13, 633–44.Google Scholar
Parnetti, L, Lowenthal, D T, Presciutti, O, et al. 1996. 1H-MRS, MRI-based hippocampal volumetry, and 99mTc-HMPAO-SPECT in normal aging, age-associated memory impairment, and probable Alzheimer's disease. J Am Geriatr Soc 44, 133–8.Google Scholar
Parnetti, L, Tarducci, R, Presciutti, O, et al. 1997. Proton magnetic resonance spectroscopy can differentiate Alzheimer's disease from normal aging. Mech Ageing Dev 97, 9–14.Google Scholar
Petersen, R C, Smith, G E, Waring, S C, Ivnik, R J, Tangalos, E G and Kokmen, E. 1999. Mild cognitive impairment: Clinical characterization and outcome. Arch Neurol 56, 303–08.Google Scholar
Pfefferbaum, A, Adalsteinsson, E, Spielman, D, Sullivan, E V and Lim, K O. 1999. In vivo brain concentrations of N-acetyl compounds, creatine, and choline in Alzheimer disease. Arch Gen Psychiatry 56, 185–92.Google Scholar
Price, J C, Klunk, W E, Lopresti, B J, et al. 2005. Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B. J Cereb Blood Flow Metab 25, 1528–47.Google Scholar
Rose, S E, Zubicaray, G I, Wang, D, et al. 1999. A 1H MRS study of probable Alzheimer's disease and normal aging: Implications for longitudinal monitoring of dementia progression. Magn Reson Imaging 17, 291–9.Google Scholar
Ross, B, Lin, A, Harris, K, Bhattacharya, P and Schweinsburg, B. 2003. Clinical experience with 13C MRS in vivo. NMR Biomed 16, 358–69.Google Scholar
Schuff, N, Amend, D, Ezekiel, F, et al. 1997. Changes of hippocampal N-acetylaspartate and volume in Alzheimer's disease: A proton MR spectroscopic imaging and MRI study. Neurology 49, 1513–21.Google Scholar
Schuff, N, Capizzano, A A, Du, A T, et al. 2003. Different patterns of N-acetylaspartate loss in subcortical ischemic vascular dementia and AD. Neurology 61, 358–64.Google Scholar
Schuff, N, Capizzano, A A, Du, A T, et al. 2002. Selective reduction of N-acetylaspartate in medial temporal and parietal lobes in AD. Neurology 58, 928–35.Google Scholar
Schuff, N, Ezekiel, F, Gamst, A C, et al. 2001. Region and tissue differences of metabolites in normally aged brain using multislice 1H magnetic resonance spectroscopic imaging. Magn Reson Med 45, 899–907.Google Scholar
Shinotoh, H, Fukushi, K, Nagatsuka, S, et al. 2003. The amygdala and Alzheimer's disease: Positron emission tomographic study of the cholinergic system. Ann N Y Acad Sci 985, 411–9.Google Scholar
Shonk, T K, Moats, R A, Gifford, P, et al. 1995. Probable Alzheimer disease: Diagnosis with proton MR spectroscopy. Radiology 195, 65–72.Google Scholar
Siger, M, Schuff, N, Zhu, X, Miller, B L and Weiner, M W. 2009. Regional myo-inositol concentration in mild cognitive impairment using 1H magnetic resonance spectroscopic imaging. Alzheimer Dis Assoc Disord 23, 57–62.Google Scholar
Simmons, M L, Frondoza, C G and Coyle, J T. 1991. Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience 45, 37–45.Google Scholar
Tedeschi, G, Bertolino, A, Lundbom, N, et al. 1996. Cortical and subcortical chemical pathology in Alzheimer's disease as assessed by multislice proton magnetic resonance spectroscopic imaging. Neurology 47, 696–704.Google Scholar
Truchot, L, Costes, S N, Zimmer, L, et al. 2007. Up-regulation of hippocampal serotonin metabolism in mild cognitive impairment. Neurology 69, 1012–7.Google Scholar
Urenjak, J, Williams, S R, Gadian, D G and Noble, M. 1993. Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J Neurosci 13, 981–9.Google Scholar
Wyper, D J, Brown, D, Patterson, J, et al. 1993. Deficits in iodine-labelled 3-quinuclidinyl benzilate binding in relation to cerebral blood flow in patients with Alzheimer's disease. Eur J Nucl Med 20, 379–86.Google Scholar
Zhu, X, Schuff, N, Kornak, J, et al. 2006. Effects of Alzheimer disease on fronto-parietal brain N-acetyl aspartate and myo-inositol using magnetic resonance spectroscopic imaging. Alzheimer Dis Assoc Disord 20, 77–85.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

  • Molecular imaging of Alzheimer's disease
    • By Norbert Schuff, Center for Imaging of Neurodegenerative Diseases at the Veterans Affairs Medical Center and Department of Radiology and Biomedical Imaging University of California San Francisco San Francisco, CA, USA
  • Edited by Martha E. Shenton, Bruce I. Turetsky, University of Pennsylvania
  • Book: Understanding Neuropsychiatric Disorders
  • Online publication: 10 January 2011
  • Chapter DOI: https://doi.org/10.1017/CBO9780511782091.026
Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

  • Molecular imaging of Alzheimer's disease
    • By Norbert Schuff, Center for Imaging of Neurodegenerative Diseases at the Veterans Affairs Medical Center and Department of Radiology and Biomedical Imaging University of California San Francisco San Francisco, CA, USA
  • Edited by Martha E. Shenton, Bruce I. Turetsky, University of Pennsylvania
  • Book: Understanding Neuropsychiatric Disorders
  • Online publication: 10 January 2011
  • Chapter DOI: https://doi.org/10.1017/CBO9780511782091.026
Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

  • Molecular imaging of Alzheimer's disease
    • By Norbert Schuff, Center for Imaging of Neurodegenerative Diseases at the Veterans Affairs Medical Center and Department of Radiology and Biomedical Imaging University of California San Francisco San Francisco, CA, USA
  • Edited by Martha E. Shenton, Bruce I. Turetsky, University of Pennsylvania
  • Book: Understanding Neuropsychiatric Disorders
  • Online publication: 10 January 2011
  • Chapter DOI: https://doi.org/10.1017/CBO9780511782091.026
Available formats
×