Clinical brain proton magnetic resonance spectroscopy for management of Alzheimer's and sub-cortical ischemic vascular dementia in older people

Waldman, Adam D.; Gurcharan, S; McConnell, James R.; Chaudry, M.Rashid; Grant, David

doi:10.1016/s0167-4943(02)00014-6

Cited by 37 publications

(21 citation statements)

References 10 publications

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“…The results replicate and extend previous SV MRS reports demonstrating the added value of measuring mI together with NAA. 12,16,18,21,24,55,64 The combined NAA/Cr and mI/Cr in parietal lobe GM by short TE 1H MRSI yielded a modest predictive value for distinguishing AD from normal subjects. In comparison, other 1H MRS studies reported classification rates ranging from 68% to 90% 10,24,47,65-68 ( Table 5).…”

Section: Value Of Using MI and Naa For Classificationmentioning

confidence: 94%

Effects of Alzheimer Disease on Fronto-parietal Brain N-acetyl Aspartate and Myo-Inositol Using Magnetic Resonance Spectroscopic Imaging

Zhu¹,

Schuff²,

Kornak³

et al. 2006

Alzheimer Disease &Amp; Associated Disorders

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Previous magnetic resonance (MR) spectroscopy studies of Alzheimer disease (AD) reporting reduced N-acetyl aspartate (NAA) and increased myo-Inositol (mI) used single voxel techniques, which have limited ability to assess the regional distribution of the metabolite abnormalities. The objective of this study was to determine the regional distribution of NAA and mI alterations in AD by using MR spectroscopic imaging. Fourteen patients with AD and 22 cognitively normal elderly were studied using structural MR imaging and MR spectroscopic imaging. Changes of NAA, mI, and various metabolite ratios were measured in frontal and parietal lobe gray matter (GM) and white matter. This study found: (1) when compared with cognitively normal subjects, AD patients had increased mI and mI/creatine (Cr) ratios primarily in parietal lobe GM, whereas frontal lobe GM and white matter were spared; (2) in the same region where mI was increased, AD patients had also decreased NAA and NAA/Cr ratios, replicating previous findings; (3) however, increased mI or mI/ Cr ratios did not correlate with decreased NAA or NAA/Cr ratios; and (4) using mI/Cr and NAA/Cr together improved sensitivity and specificity to AD from control as compared with NAA/Cr alone. In conclusion, decreased NAA and increased mI in AD are primarily localized in parietal lobe GM regions. However, the NAA and mI changes are not correlated with each other, suggesting that they represent different processes that might help staging of AD. KeywordsAlzheimer disease; short TE 1H magnetic resonance spectroscopic imaging; brain myo-Inositol Reprints: Xiaoping Zhu, MD, PhD, MR Unit, 114M, VA Medical Center/UCSF, 4150 Clement Street, San Francisco, CA 94121 (e-mail: zhupxia@itsa.ucsf.edu).. Sources of Support: Grant sponsor: NIH; Grant numbers: AG10897; AG12435; EB00207; EB00822; EB000766; Grant sponsor: VA Research: MIRECC, REAP. NIH Public Access Author ManuscriptAlzheimer Dis Assoc Disord. Author manuscript; available in PMC 2007 March 13. Published in final edited form as:Alzheimer Dis Assoc Disord. 2006 ; 20(2): 77-85. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptAlzheimer disease (AD) is characterized by accumulation of intraneuronal neurofibrillary tangles and extracellular amyloid plaques, as well as progressive loss of neurons that initially involve the hippocampal formation, temporoparietal cortex, and at later stages other cortical regions. 1-3 Such stereotypical regional spread of pathology may be delineated with imaging techniques, including structural magnetic resonance imaging (MRI), which showed brain tissue loss 4 and functional imaging by positron emission tomography (PET), which demonstrated cerebral glucose hypometabolism in AD. 5 However, neither structural MRI nor PET provides specific measures of neuronal or glial alterations.In vivo 1H magnetic resonance spectroscopy (MRS) has been used to measure levels of brain metabolites, such as N-acetyl aspartate (NAA) and myo-Inositol (mI) in AD. 6 Because NAA is found in relative...

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Section: Value Of Using MI and Naa For Classificationmentioning

confidence: 94%

Effects of Alzheimer Disease on Fronto-parietal Brain N-acetyl Aspartate and Myo-Inositol Using Magnetic Resonance Spectroscopic Imaging

Zhu¹,

Schuff²,

Kornak³

et al. 2006

Alzheimer Disease &Amp; Associated Disorders

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“…Alzheimer disease-A reasonable working hypothesis, subsequently confirmed in myriad studies, suggests that regional reductions in NAA concentration and NAA-creatine ratio are to be found in individual patients and in patient groups who test positive for clinical dementia. Patients with Alzheimer disease consistently show a 15-20% reduction in NAA/Cr (or NAA concentration) in posterior cingulate gyrus gray matter Moats et al, 1994;Shonk et al, 1995;Waldman et al, 2002). The gray matter in the region of the posterior cingulate gyrus has been found to be the most reliable for the diagnosis of this and other dementias, rather than hippocampus, the region selected for PET diagnosis, and postmortem histological examination of Alzheimer disease.…”

Section: Magnetic Resonance Spectroscopy and Imaging Of Naamentioning

confidence: 99%

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Moffett

Ross

Arun

et al. 2007

Progress in Neurobiology

1,229

1,126

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The brain is unique among organs in many respects, including its mechanisms of lipid synthesis and energy production. The nervous system-specific metabolite N-acetylaspartate (NAA), which is synthesized from aspartate and acetyl-coenzyme A in neurons, appears to be a key link in these distinct biochemical features of CNS metabolism. During early postnatal CNS development, the expression of lipogenic enzymes in oligodendrocytes, including the NAA-degrading enzyme aspartoacylase (ASPA), is increased along with increased NAA production in neurons. NAA is transported from neurons to the cytoplasm of oligodendrocytes, where ASPA cleaves the acetate moiety for use in fatty acid and steroid synthesis. The fatty acids and steroids produced then go on to be used as building blocks for myelin lipid synthesis. Mutations in the gene for ASPA result in the fatal leukodystrophy Canavan disease, for which there is currently no effective treatment. Once postnatal myelination is completed, NAA may continue to be involved in myelin lipid turnover in adults, but it also appears to adopt other roles, including a bioenergetic role in neuronal mitochondria. NAA and ATP metabolism appear to be linked indirectly, whereby acetylation of aspartate may facilitate its removal from neuronal mitochondria, thus favoring conversion of glutamate to alpha ketoglutarate which can enter the tricarboxylic acid cycle for energy production. In its role as a mechanism for enhancing mitochondrial energy production from glutamate, NAA is in a key position to act as a magnetic resonance spectroscopy marker for neuronal health, viability and number. Evidence suggests that NAA is a direct precursor for the enzymatic synthesis of the neuron specific dipeptide N-acetylaspartylglutamate, the most concentrated neuropeptide in the human brain. Other proposed roles for NAA include neuronal osmoregulation and axon-glial signaling. We propose that NAA may also be involved in brain nitrogen balance. Further research will be required to more fully understand the biochemical functions served by NAA in CNS development and activity, and additional functions are likely to be discovered.

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“…Nevertheless, some disagree with these findings [159,160] so further research is needed to verify MRSI's predictability from MCI to AD. Some researches have also affirmed the potential of MRSI to help in distinguishing different types of dementia from AD, such as FTD [161] or subcortical ischemic VD [162,163].…”

Section: Magnetic Resonance Spectroscopic Imaging (Mrsi)mentioning

confidence: 99%