The impact of demographic, clinical, genetic, and imaging variables on tau PET status

Ossenkoppele, Rik; Leuzy, Antoine; Cho, Hanna; Sudre, Carole H.; Strandberg, Olof; Smith, Ruben; Palmqvist, Sebastian; Mattsson-Carlgren, Niklas; Olsson, Tomas; Jögi, Jonas; Stormrud, Erik; Ryu, Young Hoon; Choi, Jae Yong; Boxer, Adam L.; Gorno-Tempini, Maria L.; Miller, Bruce L.; Soleimani-Meigooni, David; Iaccarino, Leonardo; La Joie, Renaud; Borroni, Edilio; Klein, Gregory; Pontecorvo, Michael J.; Devous, Michael D.; Villeneuve, Sylvia; Lyoo, Chul Hyoung; Rabinovici, Gil D.; Hansson, Oskar

doi:10.1007/s00259-020-05099-w

The impact of demographic, clinical, genetic, and imaging variables on tau PET status

Journal Article · Thu Nov 19 00:00:00 EST 2020 · European Journal of Nuclear Medicine and Molecular Imaging

DOI:https://doi.org/10.1007/s00259-020-05099-w· OSTI ID:1816071

^[1]; Leuzy, Antoine ^[2]; Cho, Hanna ^[3]; Sudre, Carole H. ^[4]; Strandberg, Olof ^[2]; Smith, Ruben ^[2]; Palmqvist, Sebastian ^[2]; Mattsson-Carlgren, Niklas ^[5]; Olsson, Tomas ^[6]; Jögi, Jonas ^[7]; Stormrud, Erik ^[8]; Ryu, Young Hoon ^[9]; Choi, Jae Yong ^[10]; Boxer, Adam L. ^[11]; Gorno-Tempini, Maria L. ^[11]; Miller, Bruce L. ^[11]; Soleimani-Meigooni, David ^[11]; Iaccarino, Leonardo ^[11]; La Joie, Renaud ^[11]; Borroni, Edilio ^[12] more »

Lund Univ. (Sweden). Clinical Memory Research Unit; Vrije Univ., Amsterdam (Netherlands). VU Univ. Medical Center. Amsterdam UMC. Amsterdam Neuroscience. Dept. of Neurology. Alzheimer Center Amsterdam; OSTI
Lund Univ. (Sweden). Clinical Memory Research Unit
Yonsei Univ., Seoul (Korea, Republic of). Gangnam Severance Hospital. Dept. of Neurology
King's College, London (United Kingdom). School of Biomedical Engineering and Imaging Sciences; Univ. College London (United Kingdom). Inst. of Neurology. Dept. of Neurodegenerative Disease. Dementia Research Centre; Univ. College London (United Kingdom). Dept. of Medical Physics. Centre for Medical Image Computing
Lund Univ. (Sweden). Clinical Memory Research Unit; Skåne Univ. Hospital, Lund (Sweden). Dept. of Neurology; Lund Univ. (Sweden). Wallenberg Centre for Molecular Medicine
Skåne Univ. Hospital, Lund (Sweden). Dept. of Radiation Physics
Skåne Univ. Hospital, Lund (Sweden). Dept. of Clinical Physiology and Nuclear Medicine
Lund Univ. (Sweden). Clinical Memory Research Unit; Skåne Univ. Hospital, Malmö (Sweden). Memory Clinic
Yonsei Univ., Seoul (Korea, Republic of). College of Medicine. Gangnam Severance Hospital. Dept. of Nuclear Medicine
Yonsei Univ., Seoul (Korea, Republic of). College of Medicine. Gangnam Severance Hospital. Dept. of Nuclear Medicine; Korea Inst. Radiological and Medical Sciences, Seoul (Korea, Republic of). Division of applied RI
Univ. of California, San Francisco, CA (United States). Dept. of Neurology, Memory and Aging Center
F. Hoffmann-La Roche Ltd, Basel (Switzerland)
Avid Radiopharmaceuticals, Philadelphia, PA (United States)
McGill Univ., Montreal, QC (Canada). Douglas Mental Health University Inst. Depts. of Psychiatry and Neurology & Neurosurgery
F. Hoffmann-La Roche Ltd, Basel (Switzerland); Univ. of California, San Francisco, CA (United States). Dept. of Radiology and Biomedical Imaging; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division

Purpose: A substantial proportion of amyloid-β (Aβ)+ patients with clinically diagnosed Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI) are tau PET–negative, while some clinically diagnosed non-AD neurodegenerative disorder (non-AD) patients or cognitively unimpaired (CU) subjects are tau PET–positive. We investigated which demographic, clinical, genetic, and imaging variables contributed to tau PET status. Methods: We included 2338 participants (430 Aβ+ AD dementia, 381 Aβ+ MCI, 370 non-AD, and 1157 CU) who underwent [¹⁸F]flortaucipir (n = 1944) or [¹⁸F]RO948 (n = 719) PET. Tau PET positivity was determined in the entorhinal cortex, temporal meta-ROI, and Braak V-VI regions using previously established cutoffs. We performed bivariate binary logistic regression models with tau PET status (positive/negative) as dependent variable and age, sex,APOEε4, Aβ status (only in CU and non-AD analyses), MMSE, global white matter hyperintensities (WMH), and AD-signature cortical thickness as predictors. Additionally, we performed multivariable binary logistic regression models to account for all other predictors in the same model. Results: Tau PET positivity in the temporal meta-ROI was 88.6% for AD dementia, 46.5% for MCI, 9.5% for non-AD, and 6.1% for CU. Among Aβ+ participants with AD dementia and MCI, lower age, MMSE score, and AD-signature cortical thickness showed the strongest associations with tau PET positivity. In non-AD and CU participants, presence of Aβ was the strongest predictor of a positive tau PET scan. Conclusion: We identified several demographic, clinical, and neurobiological factors that are important to explain the variance in tau PET retention observed across the AD pathological continuum, non-AD neurodegenerative disorders, and cognitively unimpaired persons.

View Accepted Manuscript (DOE)

Sponsoring Organization:: Alzheimer's Association; Alzheimer's Society; National Institutes of Health (NIH); Rainwater Charitable; USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1816071

Alternate ID(s):: OSTI ID: 23046007

Journal Information:: European Journal of Nuclear Medicine and Molecular Imaging, Journal Name: European Journal of Nuclear Medicine and Molecular Imaging Journal Issue: 7 Vol. 48; ISSN 1619-7070

Publisher:: Springer NatureCopyright Statement

Country of Publication:: United States

Language:: English

References (50)

Prevalence of Amyloid PET Positivity in Dementia Syndromes: A Meta-analysis Ossenkoppele, Rik; Jansen, Willemijn J.; Rabinovici, Gil D. JAMA, Vol. 313, Issue 19 https://doi.org/10.1001/jama.2015.4669	journal	May 2015
Discriminative Accuracy of [ ¹⁸ F]flortaucipir Positron Emission Tomography for Alzheimer Disease vs Other Neurodegenerative Disorders Ossenkoppele, Rik; Rabinovici, Gil D.; Smith, Ruben JAMA, Vol. 320, Issue 11 https://doi.org/10.1001/jama.2018.12917	journal	September 2018
Associations of Amyloid, Tau, and Neurodegeneration Biomarker Profiles With Rates of Memory Decline Among Individuals Without Dementia Jack, Clifford R.; Wiste, Heather J.; Therneau, Terry M. JAMA, Vol. 321, Issue 23 https://doi.org/10.1001/jama.2019.7437	journal	June 2019
Association of Apolipoprotein E ɛ4, Educational Level, and Sex With Tau Deposition and Tau-Mediated Metabolic Dysfunction in Older Adults Ramanan, Vijay K.; Castillo, Anna M.; Knopman, David S. JAMA Network Open, Vol. 2, Issue 10 https://doi.org/10.1001/jamanetworkopen.2019.13909	journal	October 2019
Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults Buckley, Rachel F.; Mormino, Elizabeth C.; Rabin, Jennifer S. JAMA Neurology, Vol. 76, Issue 5 https://doi.org/10.1001/jamaneurol.2018.4693	journal	May 2019
Association of Apolipoprotein E ε4 With Medial Temporal Tau Independent of Amyloid-β Therriault, Joseph; Benedet, Andrea L.; Pascoal, Tharick A. JAMA Neurology, Vol. 77, Issue 4 https://doi.org/10.1001/jamaneurol.2019.4421	journal	April 2020
Assessment of Demographic, Genetic, and Imaging Variables Associated With Brain Resilience and Cognitive Resilience to Pathological Tau in Patients With Alzheimer Disease Ossenkoppele, Rik; Lyoo, Chul Hyoung; Jester-Broms, Jonas JAMA Neurology, Vol. 77, Issue 5 https://doi.org/10.1001/jamaneurol.2019.5154	journal	May 2020
Positron Emission Tomography Imaging With [ ¹⁸ F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes Fleisher, Adam S.; Pontecorvo, Michael J.; Devous, Michael D. JAMA Neurology, Vol. 77, Issue 7 https://doi.org/10.1001/jamaneurol.2020.0528	journal	July 2020
Diagnostic Performance of RO948 F 18 Tau Positron Emission Tomography in the Differentiation of Alzheimer Disease From Other Neurodegenerative Disorders Leuzy, Antoine; Smith, Ruben; Ossenkoppele, Rik JAMA Neurology, Vol. 77, Issue 8 https://doi.org/10.1001/jamaneurol.2020.0989	journal	August 2020
Prevalence and Clinical Phenotype of Quadruple Misfolded Proteins in Older Adults Karanth, Shama; Nelson, Peter T.; Katsumata, Yuriko JAMA Neurology, Vol. 77, Issue 10 https://doi.org/10.1001/jamaneurol.2020.1741	journal	October 2020
Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue: Validation of PET Tracer Marquié, Marta; Normandin, Marc D.; Vanderburg, Charles R. Annals of Neurology, Vol. 78, Issue 5 https://doi.org/10.1002/ana.24517	journal	September 2015
18 F-flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: A multicenter study : Flortaucipir Tau PET in PSP Schonhaut, Daniel R.; McMillan, Corey T.; Spina, Salvatore Annals of Neurology, Vol. 82, Issue 4 https://doi.org/10.1002/ana.25060	journal	October 2017
Head-to-head comparison of tau positron emission tomography tracers [18F]flortaucipir and [18F]RO948 Smith, Ruben; Schöll, Michael; Leuzy, Antoine European Journal of Nuclear Medicine and Molecular Imaging, Vol. 47, Issue 2 https://doi.org/10.1007/s00259-019-04496-0	journal	October 2019
Prevalence of dementia disorders in the oldest-old: an autopsy study Jellinger, Kurt A.; Attems, Johannes Acta Neuropathologica, Vol. 119, Issue 4 https://doi.org/10.1007/s00401-010-0654-5	journal	March 2010
The molecular pathology of Alzheimer's disease Selkoe, Dennis J. Neuron, Vol. 6, Issue 4 https://doi.org/10.1016/0896-6273(91)90052-2	journal	April 1991
Understanding the Odd Science of Aging Kirkwood, Thomas B. L. Cell, Vol. 120, Issue 4 https://doi.org/10.1016/j.cell.2005.01.027	journal	February 2005
The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease McKhann, Guy M.; Knopman, David S.; Chertkow, Howard Alzheimer's & Dementia, Vol. 7, Issue 3 https://doi.org/10.1016/j.jalz.2011.03.005	journal	May 2011
The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease Albert, Marilyn S.; DeKosky, Steven T.; Dickson, Dennis Alzheimer's & Dementia, Vol. 7, Issue 3 https://doi.org/10.1016/j.jalz.2011.03.008	journal	April 2011
Introduction to special issue: Overview of Alzheimer's Disease Neuroimaging Initiative Weiner, Michael W.; Veitch, Dallas P. Alzheimer's & Dementia, Vol. 11, Issue 7 https://doi.org/10.1016/j.jalz.2015.05.007	journal	July 2015
Defining imaging biomarker cut points for brain aging and Alzheimer's disease Jack, Clifford R.; Wiste, Heather J.; Weigand, Stephen D. Alzheimer's & Dementia, Vol. 13, Issue 3 https://doi.org/10.1016/j.jalz.2016.08.005	journal	March 2017
NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease Jack, Clifford R.; Bennett, David A.; Blennow, Kaj Alzheimer's & Dementia, Vol. 14, Issue 4 https://doi.org/10.1016/j.jalz.2018.02.018	journal	April 2018
Imaging correlations of tau, amyloid, metabolism, and atrophy in typical and atypical Alzheimer's disease Whitwell, Jennifer L.; Graff‐Radford, Jonathan; Tosakulwong, Nirubol Alzheimer's & Dementia, Vol. 14, Issue 8 https://doi.org/10.1016/j.jalz.2018.02.020	journal	March 2018
Distinct tau PET patterns in atrophy‐defined subtypes of Alzheimer's disease Ossenkoppele, Rik; Lyoo, Chul Hyoung; Sudre, Carole H. Alzheimer's & Dementia, Vol. 16, Issue 2 https://doi.org/10.1016/j.jalz.2019.08.201	journal	January 2020
A hybrid approach to the skull stripping problem in MRI Ségonne, F.; Dale, A. M.; Busa, E. NeuroImage, Vol. 22, Issue 3 https://doi.org/10.1016/j.neuroimage.2004.03.032	journal	July 2004
Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease Maass, Anne; Landau, Susan; Baker, Suzanne L. NeuroImage, Vol. 157 https://doi.org/10.1016/j.neuroimage.2017.05.058	journal	August 2017
Inferior temporal tau is associated with accelerated prospective cortical thinning in clinically normal older adults Scott, Matthew R.; Hampton, Olivia L.; Buckley, Rachel F. NeuroImage, Vol. 220 https://doi.org/10.1016/j.neuroimage.2020.116991	journal	October 2020
Whole Brain Segmentation Fischl, Bruce; Salat, David H.; Busa, Evelina Neuron, Vol. 33, Issue 3 https://doi.org/10.1016/s0896-6273(02)00569-x	journal	January 2002
Tau PET imaging in neurodegenerative tauopathies—still a challenge Leuzy, Antoine; Chiotis, Konstantinos; Lemoine, Laetitia Molecular Psychiatry, Vol. 24, Issue 8 https://doi.org/10.1038/s41380-018-0342-8	journal	January 2019
Synergy between amyloid-β and tau in Alzheimer’s disease Busche, Marc Aurel; Hyman, Bradley T. Nature Neuroscience, Vol. 23, Issue 10 https://doi.org/10.1038/s41593-020-0687-6	journal	August 2020
Measuring the thickness of the human cerebral cortex from magnetic resonance images Fischl, B.; Dale, A. M. Proceedings of the National Academy of Sciences, Vol. 97, Issue 20 https://doi.org/10.1073/pnas.200033797	journal	September 2000
Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease Ossenkoppele, Rik; Schonhaut, Daniel R.; Schöll, Michael Brain, Vol. 139, Issue 5 https://doi.org/10.1093/brain/aww027	journal	March 2016
Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition Pontecorvo, Michael J.; Devous, Michael D.; Navitsky, Michael Brain https://doi.org/10.1093/brain/aww334	journal	January 2017
Distinct 18F-AV-1451 tau PET retention patterns in early- and late-onset Alzheimer’s disease Schöll, Michael; Ossenkoppele, Rik; Strandberg, Olof Brain, Vol. 140, Issue 9 https://doi.org/10.1093/brain/awx171	journal	July 2017
Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer’s disease Bejanin, Alexandre; Schonhaut, Daniel R.; La Joie, Renaud Brain, Vol. 140, Issue 12 https://doi.org/10.1093/brain/awx243	journal	October 2017
Tau PET in autosomal dominant Alzheimer’s disease: relationship with cognition, dementia and other biomarkers Gordon, Brian A.; Blazey, Tyler M.; Christensen, Jon Brain, Vol. 142, Issue 4 https://doi.org/10.1093/brain/awz019	journal	February 2019
Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report Nelson, Peter T.; Dickson, Dennis W.; Trojanowski, John Q. Brain, Vol. 142, Issue 6 https://doi.org/10.1093/brain/awz099	journal	April 2019
White matter hyperintensities: relationship to amyloid and tau burden Graff-Radford, Jonathan; Arenaza-Urquijo, Eider M.; Knopman, David S. Brain, Vol. 142, Issue 8 https://doi.org/10.1093/brain/awz162	journal	June 2019
The bivariate distribution of amyloid-β and tau: relationship with established neurocognitive clinical syndromes Jack, Clifford R.; Wiste, Heather J.; Botha, Hugo Brain, Vol. 142, Issue 10 https://doi.org/10.1093/brain/awz268	journal	September 2019
Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer Disease Centers, 2005–2010 Beach, Thomas G.; Monsell, Sarah E.; Phillips, Leslie E. Journal of Neuropathology & Experimental Neurology, Vol. 71, Issue 4 https://doi.org/10.1097/NEN.0b013e31824b211b	journal	April 2012
Bayesian Model Selection for Pathological Neuroimaging Data Applied to White Matter Lesion Segmentation Sudre, Carole H.; Cardoso, M. Jorge; Bouvy, Willem H. IEEE Transactions on Medical Imaging, Vol. 34, Issue 10 https://doi.org/10.1109/TMI.2015.2419072	journal	October 2015
The amyloid hypothesis for Alzheimer’s disease: a critical reappraisal: Amyloid hypothesis for Alzheimer’s disease Hardy, John Journal of Neurochemistry, Vol. 110, Issue 4 https://doi.org/10.1111/j.1471-4159.2009.06181.x	journal	May 2009
Prospective longitudinal atrophy in Alzheimer’s disease correlates with the intensity and topography of baseline tau-PET La Joie, Renaud; Visani, Adrienne V.; Baker, Suzanne L. Science Translational Medicine, Vol. 12, Issue 524 https://doi.org/10.1126/scitranslmed.aau5732	journal	January 2020
[ 18 F]AV-1451 binding in vivo mirrors the expected distribution of TDP-43 pathology in the semantic variant of primary progressive aphasia Bevan-Jones, W. R.; Cope, Thomas E.; Jones, P. Simon Journal of Neurology, Neurosurgery & Psychiatry, Vol. 89, Issue 10 https://doi.org/10.1136/jnnp-2017-316402	journal	September 2017
Greater tau load and reduced cortical thickness in APOE ε4-negative Alzheimer’s disease: a cohort study Mattsson, Niklas; Ossenkoppele, Rik; Smith, Ruben Alzheimer's Research & Therapy, Vol. 10, Issue 1 https://doi.org/10.1186/s13195-018-0403-x	journal	August 2018
Associations between quantitative [18F]flortaucipir tau PET and atrophy across the Alzheimer’s disease spectrum Timmers, Tessa; Ossenkoppele, Rik; Wolters, Emma E. Alzheimer's Research & Therapy, Vol. 11, Issue 1 https://doi.org/10.1186/s13195-019-0510-3	journal	July 2019
Tau PET in Alzheimer disease and mild cognitive impairment Cho, Hanna; Choi, Jae Yong; Hwang, Mi Song Neurology, Vol. 87, Issue 4 https://doi.org/10.1212/WNL.0000000000002892	journal	June 2016
Associations between tau, Aβ, and cortical thickness with cognition in Alzheimer disease Ossenkoppele, Rik; Smith, Ruben; Ohlsson, Tomas Neurology, Vol. 92, Issue 6 https://doi.org/10.1212/WNL.0000000000006875	journal	January 2019
Intermediate flortaucipir uptake is associated with Aβ-PET and CSF tau in asymptomatic adults McSweeney, Melissa; Pichet Binette, Alexa; Meyer, Pierre-François Neurology, Vol. 94, Issue 11 https://doi.org/10.1212/WNL.0000000000008905	journal	February 2020
Robust Locally Weighted Regression and Smoothing Scatterplots Cleveland, William S. Journal of the American Statistical Association, Vol. 74, Issue 368 https://doi.org/10.2307/2286407	journal	December 1979
Preclinical Evaluation of ¹⁸ F-RO6958948, ¹¹ C-RO6931643, and ¹¹ C-RO6924963 as Novel PET Radiotracers for Imaging Tau Aggregates in Alzheimer Disease Honer, Michael; Gobbi, Luca; Knust, Henner Journal of Nuclear Medicine, Vol. 59, Issue 4 https://doi.org/10.2967/jnumed.117.196741	journal	September 2017

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References (50)

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