Document Detail


Short echo time proton magnetic resonance spectroscopy in Alzheimer's disease: a longitudinal multiple time point study.
MedLine Citation:
PMID:  20739347     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Short echo time localized proton magnetic resonance spectroscopy provides quantification of brain metabolites, including N-acetyl-aspartate, myo-inositol, creatine/phosphocreatine and choline-containing compounds, which may be useful biomarkers for monitoring Alzheimer's disease. We aimed to quantify the rate of metabolite change in Alzheimer's disease, to assess factors influencing changes and to investigate the potential for serial magnetic resonance spectroscopy as an Alzheimer's disease trial biomarker. A total of 42 patients and 22 controls each had up to six magnetic resonance spectroscopy examinations over a 2-year period, using a midline posterior cingulate single-voxel point resolved spectroscopy sequence (1.5 T; time to repetition = 2000 ms; echo time = 30 ms; 192 averages). Metabolite ratios N-acetyl-aspartate:creatine/phosphocreatine, choline-containing compounds:creatine/phosphocreatine, and myo-inositol:creatine/phosphocreatine were measured using online software (PROBE-Q) and the N-acetyl-aspartate:myo-inositol ratio was derived. Baseline ratios were compared between patients and controls. A linear mixed model was used to quantify longitudinal changes and extended to assess the effect of age, disease severity and baseline use of acetylcholinesterase inhibitors. Patients and controls were matched for age (patients: 68.9 ± 7.2 years; controls: 69.1 ± 6.7 years); 71% of the patients were on acetylcholinesterase inhibitors at baseline; mean Mini-Mental State Examination for patients was 19.4 ± 4.1. A total of 307 spectra were acquired. In cross-sectional analyses, patients were significantly different from controls for N-acetyl-aspartate:creatine/phosphocreatine (11% lower, P < 0.001), N-acetyl-aspartate:myo-inositol (24% lower, P < 0.001), and myo-inositol:creatine/phosphocreatine (17% higher, P < 0.001). After adjustment for N-acetyl-aspartate:myo-inositol, none of the other variables differed significantly. In patients there was significant decline in N-acetyl-aspartate:creatine/phosphocreatine (mean: 2.2%/year; 95% confidence interval: 0.9-3.5) and N-acetyl-aspartate:myo-inositol (mean: 3.7%/year; 95% confidence interval: 1.7-5.7), with no evidence for influence by age, disease severity or acetylcholinesterase inhibitor use. There was significant excess decline in patients compared with controls only in N-acetyl-aspartate:myo-inositol (mean: 3.6%/year; 95% confidence interval: 0.8-6.4; P = 0.014). Between-subject standard deviation for N-acetyl-aspartate:myo-inositol was 0% for controls and 3.5%/year for patients; within-subject standard deviation for a 1 year, two-time-point study was 9.2%/year for both patients and controls. These results confirm that magnetic resonance spectroscopy can be used to quantify excess metabolite decline in Alzheimer's disease, which may provide a useful measure of disease progression. We found no evidence that age, disease severity or acetylcholinesterase inhibitor use influenced rate of decline, although numbers were small. The substantial variability in longitudinal measurements that drives sample size requirements is principally within-subject and technique related: technical developments to reduce this variability may make serial magnetic resonance spectroscopy a viable biomarker in clinical trials for Alzheimer's disease.
Authors:
Jonathan M Schott; Chris Frost; David G MacManus; Fowzia Ibrahim; Adam D Waldman; Nick C Fox
Related Documents :
2209677 - Epilepsy in multiple sclerosis.
18457847 - Fractional anisotropy values detect pyramidal tract involvement in multiple system atro...
2424237 - Quantification of the nail fold capillary abnormalities in systemic sclerosis and rayna...
11886357 - Intrathecal igg synthesis: marker of progression in multiple sclerosis patients.
7967757 - Efficacy of fluorescence in situ hybridization for detecting pml/rara gene fusion in tr...
6214847 - Lymphocyte studies in rheumatoid arthritis. v. suppressor cell function in peripheral b...
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-25
Journal Detail:
Title:  Brain : a journal of neurology     Volume:  133     ISSN:  1460-2156     ISO Abbreviation:  Brain     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-29     Completed Date:  2010-11-30     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  0372537     Medline TA:  Brain     Country:  England    
Other Details:
Languages:  eng     Pagination:  3315-22     Citation Subset:  AIM; IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Aged
Alzheimer Disease / metabolism*,  pathology*
Cross-Sectional Studies
Female
Follow-Up Studies
Humans
Longitudinal Studies
Magnetic Resonance Spectroscopy / methods*
Male
Middle Aged
Protons*
Time Factors
Grant Support
ID/Acronym/Agency:
G0601846//Medical Research Council; //Department of Health; //Medical Research Council
Chemical
Reg. No./Substance:
0/Protons
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Significance of manipulating tumour hypoxia and radiation dose rate in terms of local tumour respons...
Next Document:  Detection of Epstein-Barr virus and B-cell follicles in the multiple sclerosis brain: what you find ...