Unsupervised [18F]Flortaucipir cutoffs for tau positivity and staging in Alzheimer's disease

Eur J Nucl Med Mol Imaging. 2023 Sep;50(11):3265-3275. doi: 10.1007/s00259-023-06280-7. Epub 2023 Jun 5.

Abstract

Purpose: Several [18F]Flortaucipir cutoffs have been proposed for tau PET positivity (T+) in Alzheimer's disease (AD), but none were data-driven. The aim of this study was to establish and validate unsupervised T+ cutoffs by applying Gaussian mixture models (GMM).

Methods: Amyloid negative (A-) cognitively normal (CN) and amyloid positive (A+) AD-related dementia (ADRD) subjects from ADNI (n=269) were included. ADNI (n=475) and Geneva Memory Clinic (GMC) cohorts (n=98) were used for validation. GMM-based cutoffs were extracted for the temporal meta-ROI, and validated against previously published cutoffs and visual rating.

Results: GMM-based cutoffs classified less subjects as T+, mainly in the A- CN (<3.4% vs >28.5%) and A+ CN (<14.5% vs >42.9%) groups and showed higher agreement with visual rating (ICC=0.91 vs ICC<0.62) than published cutoffs.

Conclusion: We provided reliable data-driven [18F]Flortaucipir cutoffs for in vivo T+ detection in AD. These cutoffs might be useful to select participants in clinical and research studies.

Keywords: Alzheimer’s disease; Cutoff; Gaussian mixture model; Tau PET; Tau positivity; [18F]Flortaucipir.

MeSH terms

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

Substances

  • 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole
  • tau Proteins
  • Amyloid beta-Peptides
  • Amyloid