Discriminative accuracy of [18F]flortaucipir positron emission tomography for Alzheimer disease vs other neurodegenerative disorders

Rik Ossenkoppele, Gil D. Rabinovici, Ruben Smith, Hanna Cho, Michael Scholl, Olof Strandberg, Sebastian Palmqvist, Niklas Mattsson, Shorena Janelidze, Alexander Santillo, Tomas Ohlsson, Jonas Jogi, Richard Tsai, Renaud La Joie, Joel Kramer, Adam L. Boxer, Maria L. Gorno-Tempini, Bruce L. Miller, Jae Y. Choi, Young H. RyuChul H. Lyoo, Oskar Hansson

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125 Citations (Scopus)

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 participantswere 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 testwas the [18F]flortaucipir PET standardized uptake value ratio (SUVR) in 5 predefined regions of interest (ROIs). Cut points for tau positivitywere determined using the mean +2 SDs observed in controls and Youden Index for the contrastADdementia vs controls. MAIN OUTCOMES AND MEASURES The reference standardwas 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.

Original languageEnglish
Pages (from-to)1151-1162
Number of pages12
JournalJAMA - Journal of the American Medical Association
Volume320
Issue number11
DOIs
Publication statusPublished - 2018 Sep 18

Bibliographical note

Funding Information:
Funding/Support: Research at Lund University was supported by the European Research Council, the Swedish Research Council, the Marianne and Marcus Wallenberg Foundation, the Knut and Alice Wallenberg Foundation, the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson’s disease) at Lund University, the Swedish Brain Foundation, the Swedish Alzheimer Foundation, The Parkinson Foundation of Sweden, The Parkinson Research Foundation, the Skåne University Hospital Foundation, and the Swedish federal government under the ALF agreement. Doses of 18F-flutemetamol injection were sponsored by GE Healthcare. Work at the University of California, San Francisco was supported by National Institute on Aging grants (R01-AG045611, P50-AG023501, P01-AG19724, R01-AG038791, and U54-NS092089), the Alzheimer’s Association (AARF-16-443577), Tau Consortium, and the Michael J. Fox Foundation. Research at Gangnam Severance Hospital was financially supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP, 2015R1C1A2A01054507) and Basic Science Research Program through the NRF funded by the Ministry of Science, ICT, and Future Planning (2017R1A2B2006694). For University of California, San Francisco and the BioFINDER study, the precursor of [18F]flortaucipir was provided by AVID Radiopharmaceuticals.

Funding Information:
completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Rabinovici receives research support from Avid Radiopharmaceuticals/Eli Lilly, GE Healthcare, and Piramal. He has received speaking honoraria or consulting fees from Eisai, Genentech, Lundbeck, Merck, Putnam, and Roche. Dr Hansson reported receiving grants from the European Research Council, Swedish Research Council, the Marianne and Marcus Wallenberg Foundation, Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson’s Disease) at Lund University, Swedish Brain Foundation, Swedish Alzheimer Foundation, Parkinson Foundation of Sweden, Parkinson Research Foundation, Skåne University Hospital Foundation, and the Swedish federal government under the ALF agreement and nonfinancial support from GE Healthcare and AVID Radiopharmaceuticals. Dr Jögi reported receiving grants from the Region of Skåne. Dr La Joie reported receiving grants from the National Institutes of Health (NIH) and the Alzheimer’s Foundation. Dr Kramer reported receiving grants from the NIH. Dr Boxer receives research support from NIH grants U54NS092089, R01AG031278, R01AG038791, R01AG032306, and R01AG022983; the Tau Research Consortium; the Bluefield Project to Cure Frontotemporal Dementia; Corticobasal Degeneration Solutions; and the Alzheimer’s Association. He has served as a consultant for Abbvie, Amgen, Celgene, Ionis, Janssen, Merck, UCB, and Toyama, and received research support from Avid, Biogen, Bristol-Myers Squibb, C2N, Cortice, Forum, Genentech, Janssen, Pfizer, Eli Lilly, Roche, and TauRx. He holds Stock Options in Aeton, Alector, and Delos, and has received personal fees from Asceneuron and grants from AFTD. Dr Miller is the medical director for the John Douglas French Foundation; scientific director for the Tau Consortium; director/medical advisory board member of the Larry L. Hillblom Foundation; scientific advisory board member for the National Institute for Health Research Cambridge Biomedical Research Centre and its subunit, the Biomedical Research Unit in Dementia (UK); board member for the American Brain Foundation; director of the Global Brain Health Institute; and president of the International Society of Frontotemporal Dementia. He receives grant support from the NIH/National Institute on Aging, the Centers for Medicare & Medicaid Services, and the Quest Diagnostics Dementia Pathway Collaboration (as grants for the Memory and Aging Center). Dr Hansson has acquired research support (for the institution) from Roche, GE Healthcare, Biogen, AVID Radiopharmaceuticals, Fujirebio, and Euroimmun. In the past 2 years, he has received consultancy/ speaker fees (paid to the institution) from Lilly, Roche, and Fujirebio. No other disclosures were reported.

Publisher Copyright:
© 2018 American Medical Association. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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