Head-to-Head Comparison of Tau and Amyloid Positron Emission Tomography Visual Reads for Differential Diagnosis of Neurodegenerative Disorders: An International, Multicenter Study

David N. Soleimani-Meigooni, Ruben Smith, Karine Provost, Orit H. Lesman-Segev, Isabel Elaine Allen, Miranda K. Chen, Hanna Cho, Lauren Edwards, Shorena Janelidze, Renaud La Joie, Nidhi Mundada, Rik Ossenkoppele, Erik Stomrud, Olof Strandberg, Amelia Strom, Adam L. Boxer, Jeffrey L. Dage, Maria Luisa Gorno-Tempini, Joel H. Kramer, Bruce L. MillerJulio C. Rojas, Howard J. Rosen, Chul H. Lyoo, Oskar Hansson, Gil D. Rabinovici

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Abstract

Objective: We compared the accuracy of amyloid and [18F]Flortaucipir (FTP) tau positron emission tomography (PET) visual reads for distinguishing patients with mild cognitive impairment (MCI) or dementia with fluid biomarker support of Alzheimer's disease (AD). Methods: Participants with FTP-PET, amyloid-PET, and diagnosis of dementia-AD (n = 102), MCI-AD (n = 41), non-AD diseases (n = 76), and controls (n = 20) were included. AD status was determined independent of PET by cerebrospinal fluid or plasma biomarkers. The mean age was 66.9 years, and 44.8% were women. Three readers interpreted scans blindly and independently. Amyloid-PET was classified as positive/negative using tracer-specific criteria. FTP-PET was classified as positive with medial temporal lobe (MTL) binding as the minimum uptake indicating AD tau (tau-MTL+), positive with posterolateral temporal or extratemporal cortical binding in an AD-like pattern (tau-CTX+), or negative. The majority of scan interpretations were used to calculate diagnostic accuracy of visual reads in detecting MCI/dementia with fluid biomarker support for AD (MCI/dementia-AD). Results: Sensitivity of amyloid-PET for MCI/dementia-AD was 95.8% (95% confidence interval 91.1–98.4%), which was comparable to tau-CTX+ 92.3% (86.7–96.1%, p = 0.67) and tau-MTL+ 97.2% (93.0–99.2%, p = 0.27). Specificity of amyloid-PET for biomarker-negative healthy and disease controls was 84.4% (75.5–91.0%), which was like tau-CTX+ 88.5% (80.4–94.1%, p = 0.34), and trended toward being higher than tau-MTL+ 75.0% (65.1–83.3%, p = 0.08). Tau-CTX+ had higher specificity than tau-MTL+ (p = 0.0002), but sensitivity was lower (p = 0.02), driven by decreased sensitivity for MCI-AD (80.5% [65.1–91.2] vs. 95.1% [83.5–99.4], p = 0.03). Interpretation: Amyloid- and tau-PET visual reads have similar sensitivity/specificity for detecting AD in cognitively impaired patients. Visual tau-PET interpretations requiring cortical binding outside MTL increase specificity, but lower sensitivity for MCI-AD. ANN NEUROL 2024;96:476–487.

Original languageEnglish
Pages (from-to)476-487
Number of pages12
JournalAnnals of Neurology
Volume96
Issue number3
DOIs
Publication statusPublished - 2024 Sept

Bibliographical note

Publisher Copyright:
© 2024 American Neurological Association.

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

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