4.7 Article

Classification and prediction of clinical diagnosis of Alzheimer's disease based on MRI and plasma measures of α-/γ-tocotrienols and γ-tocopherol

期刊

JOURNAL OF INTERNAL MEDICINE
卷 273, 期 6, 页码 602-621

出版社

WILEY
DOI: 10.1111/joim.12037

关键词

Alzheimer's disease; MRI; sensitivity; specificity; tocopherols; tocotrienols

资金

  1. InnoMed
  2. European Union [FP6-2004-LIFESCIHEALTH-5]
  3. Karolinska Institutet (Sweden)
  4. Strategic Research Programme in Neuroscience StratNeuro at Karolinska Institutet
  5. Hjarnfonden
  6. Swedish Brain Power
  7. Stockholm Medical Image Laboratory and Education (SMILE)
  8. Swedish foundation Ragnhild och Einar Lundstrooms-Minne-Lindhes
  9. Swedish foundation Stohnes-Stiftelse
  10. Swedish foundation Gamla-Tjanarinnor
  11. Academy of Finland Health Research Council
  12. Perugia University (Italy)
  13. NIHR Biomedical Research Centre for Mental Health at the South London
  14. Maudsley NHS Foundation Trust
  15. Institute of Psychiatry, Kings College London
  16. Regione Umbria, Italy
  17. University of Eastern Finland for UEFBRAIN
  18. Alzheimers Research UK [ARUK-EXT2013-4] Funding Source: researchfish
  19. National Institute for Health Research [NF-SI-0512-10053] Funding Source: researchfish
  20. Novo Nordisk Fonden [NNF11OC1014884, NNF12OC1016402] Funding Source: researchfish

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Background The aim of this study was to evaluate the accuracy of combined structural magnetic resonance imaging (MRI) measures and plasma levels of vitamin E forms, including all eight natural vitamin E congeners (four tocopherols and four tocotrienols) and markers of vitamin E oxidative/nitrosative damage, in differentiating individuals with Alzheimer's disease (AD) and mild cognitive impairment (MCI) from cognitively intact control (CTL) subjects. Methods Overall, 81 patients with AD, 86 with MCI and 86 CTL individuals were enrolled from the longitudinal multicentre AddNeuroMed study. MRI and plasma vitamin E data were acquired at baseline. MRI scans were analysed using Freesurfer, an automated segmentation scheme which generates regional volume and cortical thickness measures. Orthogonal partial least squares to latent structures (OPLS), a multivariate data analysis technique, was used to analyse MRI and vitamin E measures in relation to AD and MCI diagnosis. Results The joint evaluation of MRI and plasma vitamin E measures enhanced the accuracy of differentiating individuals with AD and MCI from CTL subjects: 98.2% (sensitivity 98.8%, specificity 97.7%) for AD versus CTL, and 90.7% (sensitivity 91.8%, specificity 89.5%) for MCI versus CTL. This combination of measures also identified 85% of individuals with MCI who converted to clinical AD at follow-up after 1year. Conclusions Plasma levels of tocopherols and tocotrienols together with automated MRI measures can help to differentiate AD and MCI patients from CTL subjects, and to prospectively predict MCI conversion into AD. Our results suggest the potential role of nutritional biomarkers detected in plasmatocopherols and tocotrienolsas indirect indicators of AD pathology, and the utility of a multimodality approach.

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