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Glutamate-glutamine and GABA in brain of normal aged and patients with cognitive impairment

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An Erratum to this article was published on 09 March 2017

Abstract

Objectives

To explore the changes of glutamate-glutamine (Glx) and gamma-aminobutyric acid (GABA) in the brain in normal old age and cognitive impairment using magnetic resonance spectroscopy (MRS).

Methods

Seventeen normal young controls (NYC), 15 normal elderly controls (NEC), 21 patients with mild cognitive impairment (MCI) and 17 with Alzheimer disease (AD) patients were included in this study. Glx and GABA+ levels in the anterior cingulate cortex (ACC) and right hippocampus (rHP) were measured by using a MEGA-PRESS sequence. Glx/Cr and GABA+/Cr ratios were compared between NYC and NEC and between the three elderly groups using analysis of covariance (ANCOVA); the tissue fractions of voxels were used as covariates. The relationships between metabolite ratios and cognitive performance were analysed using Spearman correlation coefficients.

Results

For NEC and NYC groups, Glx/Cr and GABA+/Cr ratios were lower in NEC in ACC and rHP. For the three elderly groups, Glx/Cr ratio was lower in AD in ACC compared to NEC and MCI; Glx/Cr ratio was lower in AD in rHP compared to NEC. There was no significant decrease for GABA+/Cr ratio.

Conclusions

Glx and GABA levels may decrease simultaneously in normal aged, and Glx level decreased predominantly in AD, and it is helpful in the early diagnosis of AD.

Key points

• Glx and GABA levels may decrease simultaneously in normal aged.

• Glx level may decrease predominantly in Alzheimer disease.

• The balance in excitatory–inhibitory systems may be broken in AD.

• Decreased Glx level may be helpful in early diagnosis of AD.

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Abbreviations

ACC:

Anterior cingulate cortex

AD:

Alzheimer disease

Cho:

Choline

GABA:

Gamma-aminobutyric acid

Glu:

Glutamate

Gln:

Glutamine

Glx:

Glutamate-glutamine

MCI:

Mild cognitive impairment

MEGA-PRESS:

Meshcher–Garwood point resolved spectroscopy

mI:

myo-inositol

MMSE:

Minimum Mental State Examination

MOCA:

Montreal cognitive assessment

MRS:

Magnetic resonance spectroscopy

NAA:

N-acetylaspartate

NEC:

Normal elderly controls

NYC:

Normal young controls

rHP:

Right hippocampus

References

  1. Watanabe T, Shiino A, Akiguchi I (2010) Absolute quantification in proton magnetic resonance spectroscopy is useful to differentiate amnesic mild cognitive impairment from Alzheimer's disease and healthy aging. Dement Geriatr Cogn Disord 30:71–77

    Article  CAS  PubMed  Google Scholar 

  2. Dixon RM, Bradley KM, Budge MM, Styles P, Smith AD (2002) Longitudinal quantitative proton magnetic resonance spectroscopy of the hippocampus in Alzheimer's disease. Brain 125:2332–2341

    Article  PubMed  Google Scholar 

  3. Miller BL, Moats RA, Shonk T, Ernst T, Woolley S, Ross BD (1993) Alzheimer disease: depiction of increased cerebral myo-inositol with proton MR spectroscopy. Radiology 187:433–437

    Article  CAS  PubMed  Google Scholar 

  4. Nilsen LH, Melo TM, Saether O, Witter MP, Sonnewald U (2012) Altered neurochemical profile in the McGill-R-Thy1-APP rat model of Alzheimer's disease: a longitudinal in vivo 1H MRS study. J Neurochem 123:532–541

    Article  CAS  PubMed  Google Scholar 

  5. Rupsingh R, Borrie M, Smith M, Wells JL, Bartha R (2011) Reduced hippocampal glutamate in Alzheimer disease. Neurobiol Aging 32:802–810

    Article  CAS  PubMed  Google Scholar 

  6. Kantarci K, Petersen RC, Boeve BF et al (2004) 1H MR spectroscopy in common dementias. Neurology 63:1393–1398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Meyerhoff DJ, Mackay S, Constans JM et al (1994) Axonal injury and membrane alterations in Alzheimer's disease suggested by in vivo proton magnetic resonance spectroscopic imaging. Ann Neurol 36:40–47

    Article  CAS  PubMed  Google Scholar 

  8. Govindaraju V, Young K, Maudsley AA (2000) Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed 13:129–153

    Article  CAS  PubMed  Google Scholar 

  9. Mescher M, Merkle H, Kirsch J, Garwood M, Gruetter R (1998) Simultaneous in vivo spectral editing and water suppression. NMR Biomed 11:266–272

    Article  CAS  PubMed  Google Scholar 

  10. Mckhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 34:939–944

    Article  CAS  PubMed  Google Scholar 

  11. Petersen RC, Doody R, Kurz A et al (2001) Current concepts in mild cognitive impairment. Arch Neurol 58:1985–1992

    Article  CAS  PubMed  Google Scholar 

  12. Barnes J, Scahill RI, Schott JM, Frost C, Rossor MN, Fox NC (2005) Does Alzheimer's disease affect hippocampal asymmetry? Evidence from a cross-sectional and longitudinal volumetric MRI study. Dement Geriatr Cogn Disord 19:338–344

    Article  PubMed  Google Scholar 

  13. Geroldi C, Laakso MP, Decarli C et al (2000) Apolipoprotein E genotype and hippocampal asymmetry in Alzheimer's disease: a volumetric MRI study. J Neurol Neurosurg Psychiatry 68:93–96

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Edden RA, Puts NA, Harris AD, Barker PB, Evans CJ (2014) Gannet: A batch-processing tool for the quantitative analysis of gamma-aminobutyric acid–edited MR spectroscopy spectra. J Magn Reson Imaging 40:1445–1452

    Article  PubMed  Google Scholar 

  15. Cleve M, Gussew A, Reichenbach JR (2015) In vivo detection of acute pain-induced changes of GABA+ and Glx in the human brain by using functional 1H MEGA-PRESS MR spectroscopy. NeuroImage 105:67–75

    Article  CAS  PubMed  Google Scholar 

  16. Chang L, Jiang CS, Ernst T (2009) Effects of age and sex on brain glutamate and other metabolites. Magn Reson Imaging 27:142–145

    Article  CAS  PubMed  Google Scholar 

  17. Edden RA, Crocetti D, Zhu H, Gilbert DL, Mostofsky SH (2012) Reduced GABA concentration in attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 69:750–753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yoon JH, Maddock RJ, Rokem A et al (2010) GABA concentration is reduced in visual cortex in schizophrenia and correlates with orientation-specific surround suppression. J Neurosci 30:3777–3781

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Chetelat GA, Baron J (2003) Early diagnosis of Alzheimer’s disease:contribution of structural neuroimaging. NeuroImage 18:525–541

    Article  PubMed  Google Scholar 

  20. Scheff SW, Price DA (2001) Alzheimer’s disease-related synapse loss in the cingulate cortex. J Alzheimers Dis 3:495–505

    Article  PubMed  Google Scholar 

  21. Kalpouzos G, Chetelat G, Baron J et al (2009) Voxel-based mapping of brain gray matter volume and glucose metabolism profiles in normal aging. Neurobiol Aging 30:112–124

    Article  CAS  PubMed  Google Scholar 

  22. Saransaari P, Oja SS (1995) Age-related changes in the uptake and release of glutamate and aspartate in the mouse brain. Mech Ageing Dev 81:61–71

    Article  CAS  PubMed  Google Scholar 

  23. Gao F, Edden RA, Li M et al (2013) Edited magnetic resonance spectroscopy detects an age-related decline in brain GABA levels. NeuroImage 78:75–82

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Moffett JR, Namboodiri MA, Cangro CB, Neale JH (1991) Immunohisto-chemical localization of N-acetylaspartate in rat brain. Neuroreport 2:131–134

    Article  CAS  PubMed  Google Scholar 

  25. Ding X, Maudsley AA, Sabati M et al (2016) Physiological neuronal decline in healthy aging human brain – an in vivo study with MRI and short echo-time whole-brain 1 H MR spectroscopic imaging. NeuroImage 137:45–51

    Article  PubMed  Google Scholar 

  26. Brooks JC, Roberts N, Kemp GJ, Gosney M, Lye M, Whitehouse GH (2001) A proton magnetic resonance spectroscopy study of age-related changes in frontal lobe metabolite concentrations. Cereb Cortex 11:598–605

    Article  CAS  PubMed  Google Scholar 

  27. Martin WR (2007) MR spectroscopy in neurodegenerative disease. Mol Imaging Biol 9:196–203

    Article  PubMed  Google Scholar 

  28. Christiansen P, Toft P, Larsson HB, Stubgaard M, Henriksen O (1993) The concentration of N-acetyl aspartate, creatine + phosphocreatine, and choline in different parts of the brain in adulthood and senium. Magn Reson Imaging 11:799–806

    Article  CAS  PubMed  Google Scholar 

  29. Maudsley AA, Domenig C, Govind V et al (2009) Mapping of brain metabolite distributions by volumetric proton MR spectroscopic imaging (MRSI). Magn Reson Med 61:548–559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Saunders DE, Howe FA, Den Boogaart AV, Griffiths JR, Brown MM (1999) Aging of the adult humanbrain: in vivo quantitation of metabolite content with proton magnetic resonance spectroscopy. J Magn Reson Imaging 9:711–716

    Article  CAS  PubMed  Google Scholar 

  31. Fayed N, Modrego PJ, Rojassalinas G, Aguilar K (2011) Brain glutamate levels are decreased in Alzheimer's disease: a magnetic resonance spectroscopy study. Am J Alzheimers Dis Other Demen 26:450–456

    Article  PubMed  Google Scholar 

  32. Valenzuela MJ, Sachdev PS (2001) Magnetic resonance spectroscopy in AD. Neurology 56:592–598

    Article  CAS  PubMed  Google Scholar 

  33. Canas PM, Simoes AP, Rodrigues RJ, Cunha RA (2014) Predominant loss of glutamatergic terminal markers in a β-amyloid peptide model of Alzheimer's disease. Neuropharmacology 76:51–56

    Article  CAS  PubMed  Google Scholar 

  34. Proctor DT, Coulson EJ, Dodd PR (2010) Reduction in post-synaptic scaffolding PSD-95 and SAP-102 protein levels in the Alzheimer inferior temporal cortex is correlated with disease pathology. J Alzheimers Dis 21:795–811

    Article  CAS  PubMed  Google Scholar 

  35. Kashani A, Lepicard EM, Poirel O et al (2008) Loss of VGLUT1 and VGLUT2 in the prefrontal cortex is correlated with cognitive decline in Alzheimer disease. Neurobiol Aging 29:1619–1630

    Article  CAS  PubMed  Google Scholar 

  36. Bell KF, De Kort GJ, Steggerda S, Shigemoto R, Ribeirodasilva A, Cuello AC (2003) Structural involvement of the glutamatergic presynaptic boutons in a transgenic mouse model expressing early onset amyloid pathology. Neurosci Lett 353:143–147

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to acknowledge Dr. Mark A. Brown, Dr. Sinyeob Ahn, Dr. Keith Heberlein and Dr. Panli Zuo from Siemens Healthcare for providing the MEGA-PRESS sequence.

The scientific guarantor of this publication is Hongyan Ni. The authors of this manuscript declare relationships with the following companies: Tianyi Qian is a Siemens Employee. This study has received funding by National Natural Science Foundation of China (Grant No. 30870713), Tianjin Science and Technology Support Projects (Grant Nos. 16JCYBJC25900, 15ZCZDSY00520, and 13JCQNJC14400), and the Tianjin Bureau of Public Health Projects (Grant No.15KG134). No complex statistical methods were necessary for this paper. Institutional review board approval was obtained.

Written informed consent was obtained from all subjects (patients) in this study. Methodology: retrospective, case–control study, performed at one institution.

Author information

Authors and Affiliations

  1. Department of Radiology, First Central Clinical College, Tianjin Medical University, Tianjin, 300070, China

    Dandan Huang & Susan Shrestha

  2. Department of Radiology, Tianjin First Center Hospital, Tianjin, 300192, China

    Dan Liu, Jianzhong Yin & Hongyan Ni

  3. MR Collaborations NE Asia, Siemens Healthcare, Beijing, 100102, China

    Tianyi Qian

Authors
  1. Dandan Huang
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  2. Dan Liu
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Corresponding author

Correspondence to Hongyan Ni.

Additional information

The original version of this article was revised: The presentation of Fig. 3 of this article was incorrect. The corrected Fig. 3 is inserted.

Additionally, we have also changed the wording of the Acknowledgments from “This study has received funding by the National Natural Science Foundation of China (grant no. 30870713), the Tianjin Research Program of Application Foundation, Advanced Technology (grant no. 13JCQNJC14400), the Tianjin Science and Technology Support Project (grant no. 15ZCZDSY00520), and the Tianjin Bureau of Public Health (grant no. 15KG134)” to “This study has received funding by National Natural Science Foundation of China (Grant No. 30870713), Tianjin Science and Technology Support Projects (Grant Nos. 16JCYBJC25900, 15ZCZDSY00520, and 13JCQNJC14400), and the Tianjin Bureau of Public Health Projects (Grant No.15KG134)”.

An erratum to this article is available at http://dx.doi.org/10.1007/s00330-017-4753-8.

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Huang, D., Liu, D., Yin, J. et al. Glutamate-glutamine and GABA in brain of normal aged and patients with cognitive impairment. Eur Radiol 27, 2698–2705 (2017). https://doi.org/10.1007/s00330-016-4669-8

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