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. 2023 Sep;50(11):3265-3275.
doi: 10.1007/s00259-023-06280-7. Epub 2023 Jun 5.

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

Giulia Quattrini  1   2 , Clarissa Ferrari  3   4 , Michela Pievani  1 , Andrea Geviti  4 , Federica Ribaldi  5   6 , Max Scheffler  7 , Giovanni B Frisoni  5   6 , Valentina Garibotto  8   9   10 , Moira Marizzoni  11   12 ; Alzheimer’s Disease Neuroimaging Initiative
Affiliations

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

Giulia Quattrini et al. Eur J Nucl Med Mol Imaging. 2023 Sep.

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Surface rendering of the temporal meta-ROI (A) [30] and of tau spread stages I/II–VI (B) [29] used to measure tau-PET uptake. Red regions define areas used for tau-uptake measurement. White regions indicate areas included in the previous tau-spread stage
Fig. 2
Fig. 2
Percentage of subjects classified as tau positive (T+) based on different temporal meta-ROI cutoffs, and by grouping stage-based cutoffs (dashed lines). The performance of the GMM and previously published cutoffs was tested in ADNI (internal validation, A) and validated in GMC (external validation, B). Concordance with the clinical standard (i.e., visual assessment), was tested in the GMC cohort with the intra-class correlation coefficients (ICCs). The Gaussian mixture models (GMM) cutoffs showed the highest agreement with the clinical standard
Fig. 3
Fig. 3
Percentage of subjects classified as tau positive (T+) based on the different tau stages’ cutoffs. The performance of the cutoffs was tested in ADNI (internal validation, panels A, B) and GMC (external validation, panels C, D). Concordance with the clinical standard (i.e., visual assessment) was tested in the GMC cohort with intra-class correlation coefficients (ICCs; D). The Gaussian mixture models (GMM) cutoffs showed the highest agreement with the clinical standard
See this image and copyright information in PMC

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