Diagnosed mild cognitive impairment due to Alzheimer's disease with PET biomarkers of beta amyloid and neuronal dysfunction

PLoS One. 2013 Jun 14;8(6):e66877. doi: 10.1371/journal.pone.0066877. Print 2013.

Abstract

The aim of this study is to identify mild cognitive impairment (MCI) due to Alzheimer's disease (AD) using amyloid imaging of beta amyloid (Aβ) deposition and FDG imaging of reflecting neuronal dysfunction as PET biomarkers. Sixty-eight MCI patients underwent cognitive testing, [11C]-PIB PET and [18F]-FDG PET at baseline and follow-up. Regions of interest were defined on co-registered MRI. PIB distribution volume ratio (DVR) was calculated using Logan graphical analysis, and the standardized uptake value ratio (SUVR) on the same regions was used as quantitative analysis for [18F]-FDG. Thirty (44.1%) of all 68 MCI patients converted to AD over 19.2±7.1 months. The annual rate of MCI conversion was 23.4%. A positive Aβ PET biomarker significantly identified MCI due to AD in individual MCI subjects with a sensitivity (SS) of 96.6% and specificity (SP) of 42.1%. The positive predictive value (PPV) was 56.8%. A positive Aβ biomarker in APOE ε4/4 carriers distinguished with a SS of 100%. In individual MCI subjects who had a prominent impairment in episodic memory and aged older than 75 years, an Aβ biomarker identified MCI due to AD with a greater SS of 100%, SP of 66.6% and PPV of 80%, compared to FDG biomarker alone or both PET biomarkers combined. In contrast, when assessed in precuneus, both Aβ and FDG biomarkers had the greatest level of certainty for MCI due to AD with a PPV of 87.8%. The Aβ PET biomarker primarily defines MCI due to AD in individual MCI subjects. Furthermore, combined FDG biomarker in a cortical region of precuneus provides an added diagnostic value in predicting AD over a short period.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds*
  • Biomarkers / metabolism
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / metabolism
  • Cognitive Dysfunction / diagnostic imaging*
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / pathology
  • Disease Progression
  • Female
  • Fluorodeoxyglucose F18* / pharmacokinetics
  • Glucose / metabolism
  • Humans
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Radiopharmaceuticals* / pharmacokinetics
  • Sensitivity and Specificity
  • Thiazoles*

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Biomarkers
  • Radiopharmaceuticals
  • Thiazoles
  • Fluorodeoxyglucose F18
  • Glucose

Grants and funding

The authors have no support or funding to report.