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

Vol. 20, No. 2-3, 2005

View or print article as PDF (227 KB)

Medline Abstract (ID 16020946)

Medline Related Articles

Download Citation

Cited In

Original Research Article

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
Alberto Fernández^a, Juan Manuel García-Segura^{b, c}, Tomás Ortiz^a, Julia Montoya^b, Fernando Maestú^a, Pedro Gil-Gregorio^d, Pablo Campo^a, Juan Viaño^b

^aCentro de Magnetoencefalografía Dr. Pérez-Modrego, Universidad Complutense de Madrid, Madrid,
^bUnidad de Resonancia Magnética, Clínica Ntra. Sra. del Rosario, Madrid,
^cDepartamento de Bioquímica y Biología Molecular, Facultad de Biología, Universidad Complutense de Madrid, Madrid,
^dServicio de Geriatría, Hospital Universitario San Carlos de Madrid, Madrid, Spain

Address of Corresponding Author

Dement Geriatr Cogn Disord 2005;20:169-177 (DOI: 10.1159/000087094)

Key Words

Magnetoencephalography
Proton magnetic resonance spectroscopy
Alzheimer's disease
Myoinositol/N-acetyl aspartate (mI/NAA)
Delta dipole density

Abstract

Whole-head magnetoencephalographic recordings were obtained from 10 patients with Alzheimer's disease (AD) and 10 healthy controls in a resting position. Spectroscopic examinations were performed by means of a 1.5-tesla whole-body scanner in the temporoparietal regions of both hemispheres. The relationship between ¹H-MRS-based and magnetoencephalography (MEG)-based measures and their conjoined capability to improve the diagnosis of AD were investigated in this study. Logistic regression analyses were performed. Three separated logistic models were calculated for ¹H-MRS-based metabolites, low-frequency magnetic activity, and the combination of both measures. A combined myoinositol/N-acetyl aspartate (mI/NAA)-delta dipole density (DD) model predicted the diagnosis with 90% sensitivity and 100% specificity. Additionally, the combination of temporoparietal mI/NAA and delta DD values explained the variability of individuals' cognitive status. The results support the notion that a multidisciplinary approach may improve the understanding and diagnosis of AD.

References

1.: Rapoport S: Positron emission tomography in Alzheimer's disease in relation to disease pathogenesis: a critical review. Cerebrovasc Brain Metabol Rev 1991;3:297-335.
2.: Jagust WJ, Eberling JL, Reed BR, Mathis CA, Budinger TF: Clinical studies of cerebral blood flow in Alzheimer's disease. Ann NY Acad Sci 1997;826:254-262.
3.: Kidron D, Black SE, Stanchev P, Buck B, Szalai JP, Parker J, Szekely C, Bronskill MJ: Quantitative MR volumetry in Alzheimer's disease. Topographic markers and the effect of sex and education. Neurology 1997;49:1504-1512.
4.: Yamaguchi S, Meguro K, Itoh M, Hayasaka C, Shimada M, Yamazaki H, Yamadori A: Decreased cortical glucose metabolism correlates with hippocampal atrophy in Alzheimer's disease as shown by MRI and PET. J Neurol Neurosurg Psychiatry 1997;62:596-600.
5.: Jagust WJ, Haan MN, Reed BR, Eberling JL: Brain perfusion imaging predicts survival in Alzheimer's disease. Neurology 1998;151:1009-1013.
6.: Juottonen K, Laakso MP, Partanen K, Soininen H: Comparative MR analysis of the entorhinal cortex and hippocampus in diagnosing Alzheimer disease. AJNR 1999;20:139-144.
7.: Killiany RJ, Gomez-Isla T, Moss M, Kikinis R, Sandor T, Jolesz F: Use of structural magnetic resonance imaging to predict who will get Alzheimer's disease. Ann Neurol 2000;47:430-439.
8.: Parnetti L, Tarducci R, Palumbo B, Pippi M, Mastriforti R, Gobbi G, Pelliccioli GP: In vivo neurochemical characteristics of normal and pathological aging of the brain: role of magnetic resonance spectroscopy. Arch Gerontol Geriatr 1998:suppl 6;393-398.
9.: Simmons M, Frondoza CG, Coyle JT: Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience 1991;45:37-45.
10.: Miller B, Moats RA, Shonk T, Ernst T, Woolley S, Ross BD: Alzheimer's disease: depiction of increased cerebral myo-inositol with proton MR spectroscopy. Radiology 1993;187:433-437.
11.: Klunk WE, Panchalingan K, Moosy J, McLure RJ, Pettegrew JW: N-acetyl-aspartate and other amino acid metabolites in Alzheimer's disease brain: a preliminary proton nuclear magnetic resonance study. Neurology 1992;42:1578-1585.
12.: Huang W, Alexander GE, Chang L, Shetty HU, Krasuski JS, Rapoport SI, Schapiro MB: Brain metabolite concentration and dementia severity in Alzheimer's disease: a ¹H-MRS study. Neurology 2001;57:626-632.
13.: Parnetti L, Tarducci R, Presciutti O, Lowenthal DT, Pippi M, Palumbo B, Gobbi G, Pelliccioli GP, Senin U: Proton magnetic resonance spectroscopy can differentiate Alzheimer's disease from normal aging. Mech Ageing Dev 1997;97:9-14.
14.: Rain GS, Mc Connell JR, Waldman A, Grant D, Chaudry M: Brain proton spectroscopy in dementia: an aid to clinical diagnosis. Lancet 1999;353:1063-1064.
15.: Kantarci K, Jack CR, Xu YC, Campeau NG, O'Brien PC, Smith GE, Ivnik RJ, Boewe BF, Kokmen E, Tangalos EG, Petersen RC: Regional metabolic patterns in mild cognitive impairment and Alzheimer's disease: a ¹H-MRS study. Neurology 2000;55:210-217.
16.: Elbert T: Neuromagnetism; in Andrä W, Nowak H (eds): Magnetism in Medicine. New York, Wiley, 1998, pp 190-262.
17.: Berendse HW, Verbunt JPA, Scheltens P, Van Dijk BW, Jonkman EJ: Magnetoencephalographic analysis of cortical activity in Alzheimer's disease: a pilot study. Clin Neurophysiol 2000;111:604-612.
18.: Fernández A, Maestú F, Amo C, Gil P, Fehr T, Wienbruch C, Rockstroh B, Elbert T, Ortiz T: Focal temporo-parietal slow activity in Alzheimer's disease revealed by magnetoencephalography: Biol Psychiat 2002;52:764-770.
19.: Fernández A, Arrazola J, Maestú F, Amo C, Gil-Gregorio P, Wienbruch C, Ortiz T: Correlations of hippocampal atrophy and focal low frequency magnetic activity in Alzheimer's disease: a volumetric MRI-MEG study. Am J Neuroradiol 2003;24:481-487.
20.: McKhann G, Drachman D, Folstein M: Clinical diagnosis of Alzheimer's disease: report of NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984:34:939-944.
21.: Lobo A, Ezquerra V: El mini-examen cognoscitivo: un test sencillo y práctico para detectar alteraciones intelectivas en pacientes médicos. Actas Luso-Esp Psiquiatría Psicol Méd 1979;3:189-202.
22.: Webb PG, Sailasuta N, Kohler SJ: Automated single-voxel proton MRS: technical development and multisite verification. Magn Reson Med 1994;31:365-373.
23.: Provencher SW: Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 1993;30:672-679.
24.: Seeger U, Klose U, Mader I: Parameterized evaluation of macromolecules and lipids in proton MR spectroscopy of brain diseases. Magn Reson Med 2003;49:19-28.
25.: Ernst T, Kreis R, Ross BD: Absolute quantitation of water and metabolites in human brain. I. Compartments and water. Magn Reson Med 1993;b102:1-8.
26.: Kreis R, Ernst T, Ross BD: Absolute quantitation of water and metabolites in human brain. II. Metabolite concentrations. Magn Reson Med 1993;b102:9-19.
27.: Oppenhein AV, Schafer RW: Digital Signal Processing. Englewood Cliffs, Prentice-Hall, 1974.
28.: Fehr T, Kissler J, Moratti S, Wienbruch C, Rockstroh B, Elbert T: Source distribution of neuromagnetic slow waves and MEG-delta activity in schizophrenic patients. Biol Psychiatry 2001;50:108-116.
29.: Hosmer D, Lemeshow S: Applied Logistic Regression. New York, Wiley 1989.
30.: Riekkinen P, Buzsaki G, Riekkinen P, Soininen H, Partanen J: The cholinergic system and EEG slow waves. Electroencephalog Clin Neurophysiol 1991;78:89-96.
31.: Dringenberg HC: Alzheimer's disease: More than a 'cholinergic disorder' - evidence that cholinergic-monoaminergic interactions contribute to EEG slowing and dementia. Behav Brain Res 2000;115:235-249.
32.: Longo VG: Effects of scopolamine and atropine on electroencephalographic and behavioral reactions due to hypotalamic stimulation. J Pharmacol 1966;116:198-208.
33.: Shute CCD, Lewis PR: The ascending cholinergic reticular systems: neocortical, olfactory and subcortical projections. Brain 1967;90:497-520.
34.: Dierks T, Jelic V, Pascual-Marqui RD, Wahlund LO, Julin P, Linden DEJ, et al: Spatial pattern of cerebral glucose metabolism (PET) correlates with localization of intracrebral EEG-generators in Alzheimer disease. Clin Neurophysiol 2000;111:1817-1824.
35.: Gloor P, Ball G, Schaul N: Brain lesions that produce delta waves in the EEG. Neurology 1977;27:326-333.
36.: Schaul N, Gloor P, Ball G, Gotman J: The EEG in deep midline lesions. Neurology 1981;31:157-167.
37.: Hirono N, Kitagaki H, Kazui H, Hashimoto M, Mori E: Impact of white matter changes on clinical manifestation of Alzheimer's disease: a quantitative study. Stroke 2000;31:2182-2188.
38.: Bozzali M, Falini A, Franceschi M, Cercignani M, Zuffi M, Scotti G, Comi G, Filippi M: White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging. J Neurol Neurosurg Psychiatry 2002;72:742-746.
39.: Watanabe T, Akiguchi I, Yagi H, Onishi K, Kawasaki T, Shiino A, Inubushi T: Proton magnetic resonance spectroscopy and white matter hyperintensities on magnetic resonance imaging in patients with Alzheimer's disease. Ann NY Acad Sci 2002;977:423-429.
40.: Rose SE, Chen F, Chalk JB, Zelaya FO, Strugnell WE, Benson M, Semple J, Doddrell DM: Loss of connectivity in Alzheimer's disease: an evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging. J Neurol Neurosurg Psychiatry 2000;69:528-530.
41.: Shonk T, Ross BD: Role of increased cerebral myo-inositol in the dementia of Down syndrome. Magn Res Med 1995;33:858-861.
42.: Honchar MP, Vogler GP, Gish BG, Sherman WR: Evidence that phosphoinositide metabolism in rat cerebral cortex stimulated by pilocarpine, physostigmine and pargyline in vivo is not changed by chronic lithium treatment. Neurochemistry 1990;55:1521-1525.
43.: Kennedy ED, Chaliss JRA, Ragan CL, Nahorski SF: Reduced inositol polyphosphate accumulation and inositol supply induced by lithium in stimulated cerebral cortex slices. Biochem J 1990;267:781-786.
44.: Jolles J, Bothmer J, Markerink M, Ravid R: Phosphatidylinositol kinase is reduced in Alzheimer's disease. J Neurochem 1992;58:2326-2329.
45.: Ross BD, Bluml S, Cowan R, Danielsen E, Farrow N, Gruetter R: In vivo magnetic resonance spectroscopy of human brain: the biophysical basis of dementia. Biophys Chem 1997;68:161-172.

Author Contacts

Prof. Dr. Tomás Ortiz Alonso
Centro MEG Dr. Pérez-Modrego, Facultad de Medicina
Pabellón 8, avda Complutense s\n, Universidad Complutense de Madrid
ES-28040 Madrid (Spain)
Tel. +34 91 3942 292, Fax +34 91 3942 294, E-Mail cmeg@ect.ucm.es

Article Information

Accepted: March 7, 2005
Published online: July 15, 2005
Number of Print Pages : 9
Number of Figures : 3, Number of Tables : 4, Number of References : 45

Publication Details

Dementia and Geriatric Cognitive Disorders

Vol. 20, No. 2-3, Year 2005 (Cover Date: Released August 2005)

Journal Editor: Chan-Palay, V. (New York, N.Y.)
ISSN: 1420-8008 (print), 1421-9824 (Online)

For additional information: http://www.karger.com/dem

Drug Dosage / Copyright

Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.

	© 2009 S. Karger AG, Basel
	Last update: 16/8/2005