Proton MR spectroscopy detects a relative decrease of N-acetylaspartate in the medial temporal lobe of patients with AD

Background: The reduction of N-acetylaspartate (NAA) detected by proton MR spectroscopy (1H-MRS) represents a robust but unspecific marker for neuronal loss or dysfunction. Objective: To apply 1H-MRS in two brain regions that reflect the characteristic spatial distribution of neuronal loss in AD. These regions are the medial temporal lobe (MTL), which is affected early in AD, and the primary motor and sensory cortex (central region), which is affected late in the disease and might serve as an intraindividual control region in mild to moderate disease stages. Methods: Twenty patients and 18 volunteers underwent 1H-MRS in both brain areas. The metabolic ratios of NAA/creatine and choline/creatine were determined. Additionally, the metabolic ratios of the MTL were divided by the ratios of the central region to assess the relative change in the MTL in individual subjects. All ratios were correlated with psychometric test scores. Results: A significant reduction of NAA/creatine and choline/creatine ratios was detected in the MTL of patients with AD. In the central region, no significant difference between the groups was found. NAA/creatine (MTL/central region) was reduced in patients with AD and showed a correlation with the Mini-Mental State Examination and the cognitive part of the Alzheimer Disease Assessment Scale scores. Choline/creatine (MTL/central region) did not show a significant difference between groups. Conclusion: Assessing the distribution of NAA/creatine reduction guided by the expected neuropathologic change can improve the role of 1H-MRS in the assessment of AD. The disease severity can be monitored by relative reduction of NAA/creatine in the MTL in comparison with an intraindividual unaffected control region.

[1]  K. Davis,et al.  A new rating scale for Alzheimer's disease. , 1984, The American journal of psychiatry.

[2]  K O Lim,et al.  In vivo brain concentrations of N-acetyl compounds, creatine, and choline in Alzheimer disease. , 1999, Archives of general psychiatry.

[3]  J. Saunders,et al.  Double inversion recovery improves water suppression in vivo , 1993, Magnetic resonance in medicine.

[4]  G. Fein,et al.  Axonal injury and membrane alterations in Alzheimer's disease suggested by in vivo proton magnetic resonance spectroscopic imaging , 1994, Annals of neurology.

[5]  B R Rosen,et al.  1H NMR spectroscopy studies of Huntington's disease , 1998, Neurology.

[6]  P. Jolles,et al.  Regional metabolic alterations in Alzheimer's disease: an in vitro 1H NMR study of the hippocampus and cerebellum. , 1997, The journals of gerontology. Series A, Biological sciences and medical sciences.

[7]  D J Jenden,et al.  In vivo 1H MRS choline: correlation with in vitro chemistry/histology. , 1996, Life sciences.

[8]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[9]  R. Kreis,et al.  Cerebral metabolic disturbances in patients with subacute and chronic diabetes mellitus: detection with proton MR spectroscopy. , 1992, Radiology.

[10]  J. Coyle,et al.  N-acetylaspartylglutamate, N-acetylaspartate, and N-acetylated alpha-linked acidic dipeptidase in human brain and their alterations in Huntington and Alzheimer's diseases. , 1997, Molecular and chemical neuropathology.

[11]  P. Bottomley Spatial Localization in NMR Spectroscopy in Vivo , 1987, Annals of the New York Academy of Sciences.

[12]  O. Henriksen,et al.  Reduced N-acetylaspartate content in the frontal part of the brain in patients with probable Alzheimer's disease. , 1995, Magnetic resonance imaging.

[13]  M Noble,et al.  Specific Expression of N‐Acetylaspartate in Neurons, Oligodendrocyte‐Type‐2 Astrocyte Progenitors, and Immature Oligodendrocytes In Vitro , 1992, Journal of neurochemistry.

[14]  D. Arnold,et al.  Detection of cortical neuron loss in motor neuron disease by proton magnetic resonance spectroscopic imaging in vivo , 1994, Neurology.

[15]  J. Gawehn,et al.  PROTON MAGNETIC RESONANCE SPECTROSCOPY IN DEMENTIA OF ALZHEIMER TYPE , 1997, International journal of geriatric psychiatry.

[16]  G. Fein,et al.  Biochemical alterations in multiple sclerosis lesions and normal‐appearing white matter detected by in vivo 31P and 1H spectroscopic imaging , 1994, Annals of neurology.

[17]  G. Fein,et al.  Changes of hippocampal N-acetyl aspartate and volume in Alzheimer's disease , 1997, Neurology.

[18]  T. Ernst,et al.  Abnormal cerebral metabolite concentrations in patients with probable alzheimer disease , 1994, Magnetic resonance in medicine.

[19]  P A Narayana,et al.  In vivo proton magnetic resonance spectroscopy studies of human brain. , 1991, Magnetic resonance imaging.

[20]  F Träber,et al.  Proton magnetic resonance spectroscopy of the primary motor cortex in patients with motor neuron disease: subgroup analysis and follow-up measurements. , 1998, Archives of neurology.

[21]  G. Fein,et al.  Regional gray and white matter metabolite differences in subjects with AD, with subcortical ischemic vascular dementia, and elderly controls with 1H magnetic resonance spectroscopic imaging. , 1996, Archives of neurology.

[22]  G. Fein,et al.  Alzheimer disease: quantitative H-1 MR spectroscopic imaging of frontoparietal brain. , 1998, Radiology.

[23]  H. Möller,et al.  [1H-MR spectroscopic imaging in patients with clinically diagnosed Alzheimer's disease]. , 1995, RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin.

[24]  T Ernst,et al.  Frontotemporal dementia and early Alzheimer disease: differentiation with frontal lobe H-1 MR spectroscopy. , 1997, Radiology.

[25]  I. Wilkinson,et al.  Localized cerebral proton MR spectroscopy in HIV infection and AIDS. , 1994, AJNR. American journal of neuroradiology.

[26]  W. Brooks,et al.  Proton magnetic resonance spectroscopy of vascular- and Alzheimer-type dementia. , 1996, Archives of neurology.

[27]  B D Ross,et al.  Metabolic disorders of the brain in chronic hepatic encephalopathy detected with H-1 MR spectroscopy. , 1992, Radiology.

[28]  Barbara Palumbo,et al.  Proton magnetic resonance spectroscopy can differentiate Alzheimer's disease from normal aging , 1997, Mechanisms of Ageing and Development.

[29]  Pradeep Rajagopalan,et al.  Nuclear magnetic resonance spectroscopy: A review of neuropsychiatric applications , 1995, Progress in Neuro-psychopharmacology and Biological Psychiatry.

[30]  D M Doddrell,et al.  A 1H MRS study of probable Alzheimer's disease and normal aging: implications for longitudinal monitoring of dementia progression. , 1999, Magnetic resonance imaging.

[31]  K. Krishnan,et al.  Metabolic brain mapping in Alzheimer's disease using proton magnetic resonance spectroscopy , 1998, Psychiatry Research: Neuroimaging.

[32]  B D Ross,et al.  Alzheimer disease: depiction of increased cerebral myo-inositol with proton MR spectroscopy. , 1993, Radiology.

[33]  B D Ross,et al.  Probable Alzheimer disease: diagnosis with proton MR spectroscopy. , 1995, Radiology.

[34]  N. Lundbom,et al.  Cortical and subcortical chemical pathology in Alzheimer's disease as assessed by multislice proton magnetic resonance spectroscopic imaging , 1996, Neurology.

[35]  B. Miller A review of chemical issues in 1H NMR spectroscopy: N‐acetyl‐l‐aspartate, creatine and choline , 1991, NMR in biomedicine.