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

for the Alzheimer's Disease Neuroimaging Initiative, for the PREVENT-AD research group

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2245-2258
Number of pages14
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Issue number7
Publication statusPublished - 2021 Jul

Bibliographical note

Funding Information:
PREVENT-AD was launched in 2011 as a $13.5 million, 7-year public–private partnership using funds provided by McGill University and the Fonds de Recherche du Québec – Santé (FRQ-S), an unrestricted research grant from Pfizer Canada, the J.L. Levesque Foundation, the Lemaire Foundation, the Douglas Hospital Research Centre and Foundation, the Government of Canada, and the Canada Fund for Innovation. The PET scans were supported by an Alzheimer’s Association Grant, an Alzheimer Society of Canada grant, and two Canada Institutes of Health Research grants (PJT-162091 and PJT-148963).

Funding Information:
Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.

Funding Information:
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.

Funding Information:
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.

Funding Information:
CHS is supported by an Alzheimer’s Society Junior Fellowship (AS-JF-17-011).

Funding Information:
Open access funding provided by Vrije Universiteit Amsterdam. Work at Lund University was supported by the Swedish Research Council, the Knut and Alice Wallenberg foundation, the Marianne and Marcus Wallenberg foundation, the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson’s disease) at Lund University, the Swedish Alzheimer Foundation, the Swedish Brain Foundation, The Medical Faculty at Lund University, Region Skåne, The Bundy Academy, The Parkinson foundation of Sweden, The Parkinson Research Foundation, the Skåne University Hospital Foundation, and the Swedish federal government under the ALF agreement.

Funding Information:
Work at UCSF was supported by the following grants: P30-AG062422 (BLM, GDR), P01-AG019724 (BLM, GDR), R01-AG038791 (GDR), R01-NS050915 (MLGT), K99 AG065501 (RLJ), R01 AG045611 (GDR), Alzheimer’s Association AACSF-19-617663 (DSM), Rainwater Charitable Foundation (GDR).

Funding Information:
Doses of F-flutemetamol injection were sponsored by GE Healthcare in BioFINDER-1. The precursor of F-flutemetamol was sponsored by GE Healthcare in BioFINDER-2. The precursor of F-flortaucipir was provided by Avid radiopharmaceuticals. The precursor of F-RO948 was provided by Roche. 18 18 18 18

Publisher Copyright:
© 2020, The Author(s).

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging


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