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Preliminary Communication
September 18, 2018

Discriminative Accuracy of [18F]flortaucipir Positron Emission Tomography for Alzheimer Disease vs Other Neurodegenerative Disorders

Author Affiliations
  • 1Lund University, Clinical Memory Research Unit, Lund, Sweden
  • 2VU University Medical Center, Department of Neurology and Alzheimer Center, Amsterdam Neuroscience, Amsterdam, the Netherlands
  • 3Memory and Aging Center, Department of Neurology, University of California San Francisco
  • 4Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
  • 5Wallenberg Centre for Molecular and Translational Medicine and the Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden
  • 6Memory Clinic, Skåne University Hospital, Malmö, Sweden
  • 7Skåne University Hospital, Department of Radiation Physics, Lund, Sweden
  • 8Skåne University Hospital, Department of Clinical Physiology and Nuclear Medicine, Lund, Sweden
  • 9Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
  • 10Division of RI-Convergence Research, Korea Institute Radiological and Medical Sciences, Seoul, South Korea
JAMA. 2018;320(11):1151-1162. doi:10.1001/jama.2018.12917
Key Points

Question  What is the discriminative accuracy of [18F]flortaucipir positron emission tomography (PET) for differentiating Alzheimer disease dementia from other neurodegenerative disorders?

Finding  In this multicenter cross-sectional study that included 719 participants, the use of [18F]flortaucipir PET had an estimated sensitivity of 89.9% and specificity of 90.6% for Alzheimer disease vs other neurodegenerative diseases, and outperformed established volumetric magnetic resonance imaging measures.

Meaning  Although the [18F]flortaucipir PET scan was able to discriminate Alzheimer disease from other neurodegenerative diseases, further research in clinically more representative populations is needed to understand its potential utility in patient care.

Abstract

Importance  The positron emission tomography (PET) tracer [18F]flortaucipir allows in vivo quantification of paired helical filament tau, a core neuropathological feature of Alzheimer disease (AD), but its diagnostic utility is unclear.

Objective  To examine the discriminative accuracy of [18F]flortaucipir for AD vs non-AD neurodegenerative disorders.

Design, Setting, and Participants  In this cross-sectional study, 719 participants were recruited from 3 dementia centers in South Korea, Sweden, and the United States between June 2014 and November 2017 (160 cognitively normal controls, 126 patients with mild cognitive impairment [MCI], of whom 65.9% were amyloid-β [Aβ] positive [ie, MCI due to AD], 179 patients with AD dementia, and 254 patients with various non-AD neurodegenerative disorders).

Exposures  The index test was the [18F]flortaucipir PET standardized uptake value ratio (SUVR) in 5 predefined regions of interest (ROIs). Cut points for tau positivity were determined using the mean +2 SDs observed in controls and Youden Index for the contrast AD dementia vs controls.

Main Outcomes and Measures  The reference standard was the clinical diagnosis determined at the specialized memory centers. In the primary analysis, the discriminative accuracy (ie, sensitivity and specificity) of [18F]flortaucipir was examined for AD dementia vs all non-AD neurodegenerative disorders. In secondary analyses, the area under the curve (AUC) of [18F]flortaucipir SUVR was compared with 3 established magnetic resonance imaging measures (hippocampal volumes and AD signature and whole-brain cortical thickness), and sensitivity and specificity of [18F]flortaucipir in MCI due to AD vs non-AD neurodegenerative disorders were determined.

Results  Among 719 participants, the overall mean (SD) age was 68.8 (9.2) years and 48.4% were male. The proportions of patients who were amyloid-β positive were 26.3%, 65.9%, 100%, and 23.8% among cognitively normal controls, patients with MCI, patients with AD dementia, and patients with non-AD neurodegenerative disorders, respectively. [18F]flortaucipir uptake in the medial-basal and lateral temporal cortex showed 89.9% (95% CI, 84.6%-93.9%) sensitivity and 90.6% (95% CI, 86.3%-93.9%) specificity using the threshold based on controls (SUVR, 1.34), and 96.8% (95% CI, 92.0%-99.1%) sensitivity and 87.9% (95% CI, 81.9%-92.4%) specificity using the Youden Index–derived cutoff (SUVR, 1.27) for distinguishing AD dementia from all non-AD neurodegenerative disorders. The AUCs for all 5 [18F]flortaucipir ROIs were higher (AUC range, 0.92-0.95) compared with the 3 volumetric MRI measures (AUC range, 0.63-0.75; all ROIs P < .001). Diagnostic performance of the 5 [18F]flortaucipir ROIs were lower in MCI due to AD (AUC range, 0.75-0.84).

Conclusions and Relevance  Among patients with established diagnoses at a memory disorder clinic, [18F]flortaucipir PET was able to discriminate AD from other neurodegenerative diseases. The accuracy and potential utility of this test in patient care require further research in clinically more representative populations.

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