title: Global N-acetylaspartate in normal subjects, mild cognitive impairment and Alzheimer's disease patients.
abstract: BACKGROUND
  Mild cognitive impairment (MCI) is an intermediary state on the way to Alzheimer's disease (AD). Little is known about whole brain concentration of the neuronal marker, N-acetylaspartate (NAA) in MCI patients.
  
  
  OBJECTIVE
  To test the hypothesis that since MCI and AD are both neurodegenerative, quantification of the NAA in their whole brain (WBNAA) could differentiate them from cognitively-intact matched controls.
  
  
  METHODS
  Proton MR spectroscopy to quantify the WBNAA was applied to 197 subjects (86 females) 72.6 ± 8.4 years old (mean ± standard deviation). Of these, 102 were cognitively intact, 42 diagnosed as MCI, and 53 as probable AD. Their WBNAA amounts were converted into absolute concentration by dividing with the brain volume segmented from the MRI that also yielded the fractional brain volume (fBPV), an atrophy metric.
  
  
  RESULTS
  WBNAA concentration of MCI and AD patients (10.5 ± 3.0 and 10.1 ± 2.9 mM) were not significantly different (p = 0.85). They were, however, highly significantly 25-29% lower than the 14.1 ± 2.4 mM of normal matched controls (p < 10-4). The fBPV of MCI and AD patients (72.9 ± 4.9 and 69.9 ± 4.7%) differed significantly from each other (4%, p = 0.02) and both were significantly lower than the 74.6 ± 4.4% of normal elderly (2%, p = 0.003 for MCI; 6%, p < 10-4 for AD). ROC curve analysis has shown WBNAA to have 70.5% sensitivity and 84.3% specificity to differentiate MCI or AD patients from normal elderly versus just 68.4 and 65.7% for fBPV.
  
  
  CONCLUSIONS
  Low WBNAA in MCI patients compared with cognitively normal contemporaries may indicate early neuronal damage accumulation and supports the notion of MCI as an early stage of AD. It also suggests WBNAA as a potential marker of early AD pathology.
authors.affiliation: Department of Radiology, New York University School of Medicine, New York, NY, USA Department of Psychiatry, New York University School of Medicine, New York, NY, USA.
authors.forename: Lidia
authors.initials: L
authors.lastname: Glodzik
authors.affiliation: Department of Neurology and Neuroradiology, University Hospital Basel, Basel, Switzerland Department of Geriatrics, University Hospital Basel, Basel, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Sollberger
authors.affiliation: Department of Neurology and Neuroradiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Achim
authors.initials: A
authors.lastname: Gass
authors.affiliation: Department of Radiology, New York University School of Medicine, New York, NY, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Gokhale
authors.affiliation: Department of Radiology, New York University School of Medicine, New York, NY, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Rusinek
authors.affiliation: Department of Radiology, New York University School of Medicine, New York, NY, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Babb
authors.affiliation: Department of Neurology and Neuroradiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Jochen G
authors.initials: JG
authors.lastname: Hirsch
authors.affiliation: Department of Neurology and Neuroradiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Amann
authors.affiliation: Department of Geriatrics, University Hospital Basel, Basel, Switzerland.
authors.forename: Andreas U
authors.initials: AU
authors.lastname: Monsch
authors.affiliation: Department of Radiology, New York University School of Medicine, New York, NY, USA.
authors.forename: Oded
authors.initials: O
authors.lastname: Gonen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D015415:Biomarkers; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D060825:Cognitive Dysfunction / Q000378:metabolism*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D001224:Aspartic Acid; C000179:N-acetylaspartate
keywords: Alzheimer's disease; N-acetylaspartate; magnetic resonance spectroscopy; mild cognitive impairment; normal aging