JAMA. 2018 Sep 18;320(11):1151-1162. doi: 10.1001/jama.2018.12917.
Ossenkoppele R1,2, Rabinovici GD3, Smith R1, Cho H4, Schöll M1,5, Strandberg O1, Palmqvist S1, Mattsson N1,6, Janelidze S1, Santillo A1, Ohlsson T7, Jögi J8, Tsai R3, La Joie R3, Kramer J3, Boxer AL3, Gorno-Tempini ML3, Miller BL3, Choi JY9,10, Ryu YH9, Lyoo CH4, Hansson O1,6.
Author information
1
Lund University, Clinical Memory Research Unit, Lund, Sweden.
2
VU University Medical Center, Department of Neurology and Alzheimer Center, Amsterdam Neuroscience, Amsterdam, the Netherlands.
3
Memory and Aging Center, Department of Neurology, University of California San Francisco.
4
Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
5
Wallenberg Centre for Molecular and Translational Medicine and the Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden.
6
Memory Clinic, Skåne University Hospital, Malmö, Sweden.
7
Skåne University Hospital, Department of Radiation Physics, Lund, Sweden.
8
Skåne University Hospital, Department of Clinical Physiology and Nuclear Medicine, Lund, Sweden.
9
Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
10
Division of RI-Convergence Research, Korea Institute Radiological and Medical Sciences, Seoul, South Korea.
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.
PMID: 30326496 PMCID: PMC6233630 [Available on 2019-03-18] DOI: 10.1001/jama.2018.12917
[Indexed for MEDLINE]
Ossenkoppele R1,2, Rabinovici GD3, Smith R1, Cho H4, Schöll M1,5, Strandberg O1, Palmqvist S1, Mattsson N1,6, Janelidze S1, Santillo A1, Ohlsson T7, Jögi J8, Tsai R3, La Joie R3, Kramer J3, Boxer AL3, Gorno-Tempini ML3, Miller BL3, Choi JY9,10, Ryu YH9, Lyoo CH4, Hansson O1,6.
Author information
1
Lund University, Clinical Memory Research Unit, Lund, Sweden.
2
VU University Medical Center, Department of Neurology and Alzheimer Center, Amsterdam Neuroscience, Amsterdam, the Netherlands.
3
Memory and Aging Center, Department of Neurology, University of California San Francisco.
4
Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
5
Wallenberg Centre for Molecular and Translational Medicine and the Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden.
6
Memory Clinic, Skåne University Hospital, Malmö, Sweden.
7
Skåne University Hospital, Department of Radiation Physics, Lund, Sweden.
8
Skåne University Hospital, Department of Clinical Physiology and Nuclear Medicine, Lund, Sweden.
9
Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
10
Division of RI-Convergence Research, Korea Institute Radiological and Medical Sciences, Seoul, South Korea.
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.
PMID: 30326496 PMCID: PMC6233630 [Available on 2019-03-18] DOI: 10.1001/jama.2018.12917
[Indexed for MEDLINE]
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