Skip to main content Accessibility help
×
Home
  • Print publication year: 2010
  • Online publication date: January 2011

25 - Molecular imaging of Alzheimer's disease

from Section IV - Cognitive Disorders

Summary

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). Proton magnetic resonance spectroscopic imaging (1H MRSI) measures have the potential of offering a relatively direct window into neurochemical alterations in the brain. This chapter reviews key findings of 1H MRSI in AD, MCI and aging, and discusses the potential value of this technology for diagnosis and prognosis of AD as well as for the assessment of therapeutic intervention. Other promising neurochemical imaging modalities that directly probe neurotransmitter systems using radioactive positron emission tomography (PET) tracers and amyloid PET imaging are also discussed. Overall, MRS is a promising investigational technique in dementia and related cognitive disorders to provide unique measures of multivariate spectroscopic profiles of the brain.
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.
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.
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.
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.
Blakely, R D and Coyle, J T. 1988. The neurobiology of N-acetylaspartylglutamate. Int Rev Neurobiol 30, 39–100.
Braak, H and Braak, E. 1998. Evolution of neuronal changes in the course of Alzheimer's disease. J Neural Transm Suppl 53, 127–40.
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.
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.
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.
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.
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.
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.
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.
Engelborghs, S and Deyn, P P. 1997. The neurochemistry of Alzheimer's disease. Acta Neurol Belg 97, 67–84.
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.
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.
Ferri, C P, Prince, M, Brayne, C, et al. 2005. Global prevalence of dementia: A Delphi consensus study. Lancet 366, 2112–7.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Klein, J. 2000. Membrane breakdown in acute and chronic neurodegeneration: Focus on choline-containing phospholipids. J Neural Transm 107, 1027–63.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Nordberg, A. 1993. Clinical studies in Alzheimer patients with positron emission tomography. Behav Brain Res 57, 215–24.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Ross, B, Lin, A, Harris, K, Bhattacharya, P and Schweinsburg, B. 2003. Clinical experience with 13C MRS in vivo. NMR Biomed 16, 358–69.
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.
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.
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.
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.
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.
Shonk, T K, Moats, R A, Gifford, P, et al. 1995. Probable Alzheimer disease: Diagnosis with proton MR spectroscopy. Radiology 195, 65–72.
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.
Simmons, M L, Frondoza, C G and Coyle, J T. 1991. Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience 45, 37–45.
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.
Truchot, L, Costes, S N, Zimmer, L, et al. 2007. Up-regulation of hippocampal serotonin metabolism in mild cognitive impairment. Neurology 69, 1012–7.
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.
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.
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.