Quantitative Brain Amyloid Measures Predict Time-to-Progression from Amnestic Mild Cognitive Impairment to Alzheimer's Disease

J Alzheimers Dis. 2019;70(2):477-486. doi: 10.3233/JAD-190070.

Abstract

Background: This study was designed to investigate factors that predict progression from amnestic mild cognitive impairment (aMCI) to probable Alzheimer's disease (AD).

Objective: We studied the usefulness of quantitative assessment of amyloid burden measured by Florbetapir PET scan.

Methods: The study cohort consisted of aMCI participants older than 65 and those with available Florbetapir PET scan at diagnosis from the ADNI database (http://adni.loni.usc.edu). To assess the prognostic impact of amyloid burden, a staging system based on the global SUVr of the PET scan was applied. We defined the stages as: stage I, negative amyloid scan; stage II, positive amyloid in 1st tertile; stage III, positive amyloid in 2nd tertile; and stage IV, positive amyloid in 3rd tertile.

Results: Of 250 eligible aMCI subjects (age 74.1±5.4, female n = 105), 71 (28.4%) were diagnosed with probable AD within 3 years. Higher amyloid stages showed faster cognitive decline by Kaplan-Meier analysis. In multivariate Cox analysis, with stage I as a reference, the hazard ratio (HR) increased as the stage increased: stage II (HR, 4.509; p = 0.015), stage III (HR, 7.616; p = 0.001), and stage IV (HR, 9.421; p < 0.001). Along with amyloid stage, ApoE ɛ4 (HR, 1.943; p = 0.031), score of CDR-SB (HR, 1.845; p < 0.001) and ADAS 11 (HR, 1.144; p < 0.001), and hippocampal volume (HR, 0.002; p = 0.005) were also identified as predictors of dementia progression in aMCI subjects.

Conclusions: Large amyloid burden measured from amyloid PET scan could be a predictor of faster cognitive decline in aMCI patients.

Keywords: Alzheimer’s disease; Florbetapir; amyloid; mild cognitive impairment; positron emission tomography.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / metabolism*
  • Cohort Studies
  • Disease Progression*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Peptide Fragments / metabolism*
  • Positron-Emission Tomography / trends
  • Time Factors

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)