. 2021 Jul;48(7):2245-2258.

doi: 10.1007/s00259-020-05099-w. Epub 2020 Nov 19.

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

Rik Ossenkoppele^{1

2}, Antoine Leuzy³, Hanna Cho⁴, Carole H Sudre^{5

6

7}, Olof Strandberg³, Ruben Smith³, Sebastian Palmqvist³, Niklas Mattsson-Carlgren^{3

8

9}, Tomas Olsson¹⁰, Jonas Jögi¹¹, Erik Stormrud^{3

12}, Young Hoon Ryu¹³, Jae Yong Choi^{13

14}; Alzheimer’s Disease Neuroimaging Initiative; PREVENT-AD research group; Adam L Boxer¹⁵, Maria L Gorno-Tempini¹⁵, Bruce L Miller¹⁵, David Soleimani-Meigooni¹⁵, Leonardo Iaccarino¹⁵, Renaud La Joie¹⁵, Edilio Borroni¹⁶, Gregory Klein¹⁶, Michael J Pontecorvo¹⁷, Michael D Devous Sr¹⁷, Sylvia Villeneuve¹⁸, Chul Hyoung Lyoo⁴, Gil D Rabinovici^{16

19

20}, Oskar Hansson^{21

22}

Affiliations

¹ Clinical Memory Research Unit, Lund University, Lund, Sweden. r.ossenkoppele@amsterdamumc.nl.
² Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, VU University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. r.ossenkoppele@amsterdamumc.nl.
³ Clinical Memory Research Unit, Lund University, Lund, Sweden.
⁴ Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
⁵ School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.
⁶ Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
⁷ Centre for Medical Image Computing, Department of Medical Physics, University College London, London, UK.
⁸ Department of Neurology, Skåne University Hospital, Lund, Sweden.
⁹ Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden.
¹⁰ Department of Radiation Physics, Skåne University Hospital, Lund, Sweden.
¹¹ Department of Clinical Physiology and Nuclear Medicine, Skåne University Hospital, Lund, Sweden.
¹² Memory Clinic, Skåne University Hospital, Malmö, Sweden.
¹³ Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
¹⁴ Division of applied RI, Korea Institute Radiological and Medical Sciences, Seoul, South Korea.
¹⁵ Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, USA.
¹⁶ F. Hoffmann-La Roche Ltd, Basel, Switzerland.
¹⁷ Avid Radiopharmaceuticals, Philadelphia, PA, USA.
¹⁸ Departments of Psychiatry and Neurology & Neurosurgery, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
¹⁹ Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, USA.
²⁰ Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
²¹ Clinical Memory Research Unit, Lund University, Lund, Sweden. oskar.hansson@med.lu.se.
²² Memory Clinic, Skåne University Hospital, Malmö, Sweden. oskar.hansson@med.lu.se.

PMID: 33215319
PMCID: PMC8131404
DOI: 10.1007/s00259-020-05099-w

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

Rik Ossenkoppele et al. Eur J Nucl Med Mol Imaging. 2021 Jul.

. 2021 Jul;48(7):2245-2258.

doi: 10.1007/s00259-020-05099-w. Epub 2020 Nov 19.

Authors

Affiliations

¹ Clinical Memory Research Unit, Lund University, Lund, Sweden. r.ossenkoppele@amsterdamumc.nl.
² Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, VU University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. r.ossenkoppele@amsterdamumc.nl.
³ Clinical Memory Research Unit, Lund University, Lund, Sweden.
⁴ Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
⁵ School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.
⁶ Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
⁷ Centre for Medical Image Computing, Department of Medical Physics, University College London, London, UK.
⁸ Department of Neurology, Skåne University Hospital, Lund, Sweden.
⁹ Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden.
¹⁰ Department of Radiation Physics, Skåne University Hospital, Lund, Sweden.
¹¹ Department of Clinical Physiology and Nuclear Medicine, Skåne University Hospital, Lund, Sweden.
¹² Memory Clinic, Skåne University Hospital, Malmö, Sweden.
¹³ Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
¹⁴ Division of applied RI, Korea Institute Radiological and Medical Sciences, Seoul, South Korea.
¹⁵ Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, USA.
¹⁶ F. Hoffmann-La Roche Ltd, Basel, Switzerland.
¹⁷ Avid Radiopharmaceuticals, Philadelphia, PA, USA.
¹⁸ Departments of Psychiatry and Neurology & Neurosurgery, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
¹⁹ Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, USA.
²⁰ Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
²¹ Clinical Memory Research Unit, Lund University, Lund, Sweden. oskar.hansson@med.lu.se.
²² Memory Clinic, Skåne University Hospital, Malmö, Sweden. oskar.hansson@med.lu.se.

PMID: 33215319
PMCID: PMC8131404
DOI: 10.1007/s00259-020-05099-w

Abstract

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.

Keywords: Alzheimer’s disease; Aβ; Dementia; MCI; PET; Tau.

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Conflict of interest statement

OH has acquired research support (for the institution) from Roche, Pfizer, GE Healthcare, Biogen, Eli Lilly, and AVID Radiopharmaceuticals. In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Biogen and Roche.

GDR receives research support from NIH, Alz Assoc, American College of Radiology, Avid Radiopharmaceuticals, GE Healthcare, Life Molecular Imaging. In the past 2 years he has received consulting fees from Axon Neurosciences, Eisai, GE Healthcare, Johnson & Johnson, and Merck. He is an Associate Editor for JAMA Neurology.

ALB receives research support from NIH (R01AG038791, U19AG063911), the Tau Research Consortium, the Association for Frontotemporal Degeneration, and the Bluefield Project to Cure Frontotemporal Dementia. He has served as a consultant for AGTC, Alector, Arkuda, Arvinas, Bioage, Ionis, Lundbeck, Passage BIO, Samumed, Ono, Sangamo, Stealth, Third Rock, Transposon, UCB, and Wave, and received research support from Avid, Eisai, Biogen, and Roche.

MJP and MDD are employees of Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly and Company, and are minor stockholders in Eli Lilly.

EB and GK are employees of F. Hoffmann-La Roche Ltd.

The other authors report no conflict of interest.

Figures

**Fig. 1**
The y-axis represents the SUVR values for [¹⁸F]flortaucipir (FTP, panel a–c) and [¹⁸F]RO948 (panel d–f) for the entorhinal cortex (a and d), temporal meta-ROI (b and e), and Braak V/VI ROI for Aβ+ Alzheimer’s disease (AD) dementia, Aβ+ MCI, non-AD neurodegenerative disorders, and cognitively unimpaired (CU) participants. The percentages on top of each panel represent the proportion of tau PET–positive cases based on previously established cutoffs

**Fig. 2**
The graphs show non-linear associations between tau PET uptake and MMSE scores for both [¹⁸F]flortaucipir and [¹⁸F]RO948. The horizontal lines (dotted for [¹⁸F]flortaucipir and dashed for [¹⁸F]RO948) indicate previously established cutoffs for tau PET positivity, while the vertical lines indicate the MMSE score at which the 95% confidence interval of the slope no longer overlaps with the respective tau PET cutoff for each tracer

See this image and copyright information in PMC

References

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

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

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