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

Ossenkoppele, Rik LU ; Rabinovici, Gil D. ; Smith, Ruben LU ; Cho, Hanna ; Scholl, Michael LU ; Strandberg, Olof LU ; Palmqvist, Sebastian LU ; Mattsson, Niklas LU ; Janelidze, Shorena LU and Santillo, Alexander LU , et al. (2018) In JAMA - Journal of the American Medical Association 320(11). p.1151-1162
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... (More)

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.

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320
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American Medical Association
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  • scopus:85053498433
  • pmid:30326496
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0098-7484
DOI
10.1001/jama.2018.12917
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English
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2018-10-11 08:14:44
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@article{e0b8a798-e61f-4548-ac5b-494f2d4d17f0,
  abstract     = {<p>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 &lt; .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.</p>},
  author       = {Ossenkoppele, Rik and Rabinovici, Gil D. and Smith, Ruben and Cho, Hanna and Scholl, Michael and Strandberg, Olof and Palmqvist, Sebastian and Mattsson, Niklas and Janelidze, Shorena and Santillo, Alexander and Ohlsson, Tomas and Jogi, Jonas and Tsai, Richard and La Joie, Renaud and Kramer, Joel and Boxer, Adam L. and Gorno-Tempini, Maria L. and Miller, Bruce L. and Choi, Jae Y. and Ryu, Young H. and Lyoo, Chul H. and Hansson, Oskar},
  issn         = {0098-7484},
  language     = {eng},
  month        = {09},
  number       = {11},
  pages        = {1151--1162},
  publisher    = {American Medical Association},
  series       = {JAMA - Journal of the American Medical Association},
  title        = {Discriminative accuracy of [<sup>18</sup>F]flortaucipir positron emission tomography for Alzheimer disease vs other neurodegenerative disorders},
  url          = {http://dx.doi.org/10.1001/jama.2018.12917},
  doi          = {10.1001/jama.2018.12917},
  volume       = {320},
  year         = {2018},
}