Amyloid biomarkers as predictors of conversion from mild cognitive impairment to Alzheimer's dementia: a comparison of methods

Alzheimers Res Ther. 2020 Nov 19;12(1):155. doi: 10.1186/s13195-020-00721-3.

Abstract

Background: Amyloid-β (Aβ) PET is an established predictor of conversion from mild cognitive impairment (MCI) to Alzheimer's dementia (AD). We compared three PET (including an approach based on voxel-wise Cox regression) and one cerebrospinal fluid (CSF) outcome measures in their predictive power.

Methods: Datasets were retrieved from the ADNI database. In a training dataset (N = 159), voxel-wise Cox regression and principal component analyses were used to identify conversion-related regions (Cox-VOI and AD conversion-related pattern (ADCRP), respectively). In a test dataset (N = 129), the predictive value of mean normalized 18F-florbetapir uptake (SUVR) in AD-typical brain regions (composite SUVR) or the Cox-VOI and the pattern expression score (PES) of ADCRP and CSF Aβ42/Aβ40 as predictors were compared by Cox models (corrected for age and sex).

Results: All four Aβ measures were significant predictors (p < 0.001). Prediction accuracies (Harrell's c) showed step-wise significant increases from Cox-SUVR (c = 0.71; HR = 1.84 per Z-score increase), composite SUVR (c = 0.73; HR = 2.18), CSF Aβ42/Aβ40 (c = 0.75; HR = 3.89) to PES (c = 0.77; HR = 2.71).

Conclusion: The PES of ADCRP is the most predictive Aβ PET outcome measure, comparable to CSF Aβ42/Aβ40, with a slight but statistically significant advantage.

Keywords: Alzheimer’s dementia; Amyloid biomarkers; Conversion prediction; Mild cognitive impairment; PET image evaluation.

MeSH terms

  • Alzheimer Disease* / complications
  • Alzheimer Disease* / diagnostic imaging
  • Amyloid beta-Peptides
  • Biomarkers
  • Cognitive Dysfunction* / diagnostic imaging
  • Humans
  • Positron-Emission Tomography

Substances

  • Amyloid beta-Peptides
  • Biomarkers