The prevalence of tau‐PET positivity in aging and dementia

Abstract Background Tau‐PET imaging allows in‐vivo detection of neurofibrillary tangles. One tau‐PET tracer (i.e., [ 18 F]flortaucipir) has received FDA‐approval for clinical use, and multiple other tau‐PET tracers have been implemented into clinical trials for participant selection and/or as a primary or secondary outcome measure. To optimize future use of tau‐PET, it is essential to understand how demographic, clinical and genetic factors affect tau‐PET‐positivity rates. Method This large‐scale multi‐center study includes 9713 participants from 35 cohorts worldwide who underwent tau‐PET with [ 18 F]flortaucipir (n=6420), [ 18 F]RO948 (n=1999), [ 18 F]MK6240 (n=878) or [ 18 F]PI2620 (n=416) (Table 1). We analyzed individual‐level tau‐PET SUVR data using a cerebellar reference region that were processed either centrally (n=3855) or by each cohort (n=5858). We computed cohort‐specific SUVR thresholds based on the mean + 2 standard deviations in a temporal meta‐region of amyloid‐negative cognitively normal (CN) individuals aged >50. Logistic generalized estimating equations were used to estimate tau‐PET‐positivity probabilities, using an exchangeable correlation structure to account for within‐cohort correlations. Analyses were performed with (interactions between) age, amyloid‐status, and APOE‐ε4 carriership as independent variables, stratified for syndrome diagnosis. Result The study included 5962 CN participants (7.5% tau‐PET‐positive), 1683 participants with mild cognitive impairment (MCI, 33.8% tau‐PET‐positive) and 2068 participants with a clinical diagnosis of dementia (62.1% tau‐PET‐positive) (Figure 1). From age 60 to 80 years, the estimated prevalence of tau‐PET‐positivity increased from 1.2% [95% CI: 0.9%‐1.5%] to 3.7% [2.3%‐5.1%] among CN amyloid‐negative participants; and from 16.4% [10.8%‐22.1%] to 20.5% [18.8%‐22.2%] among CN amyloid‐positive participants. Among amyloid‐negative participants with MCI and dementia, from age 60 to 80 years, the estimated prevalence of tau‐PET‐positivity increased from 3.5% [1.6%‐5.3%] to 11.8% [7.1%‐16.5%] and from 12.6% [4.5%‐20.7%] to 15.9% [6.7%‐25.1%] respectively. In contrast, among amyloid‐positive participants with MCI and dementia, from age 60 to 80 years, the estimated prevalence of tau‐PET‐positivity decreased from 66.5% [57.0%‐76.0%] to 48.3% [42.9%‐53.8%] and from 92.3% [88.7%‐95.9%] to 73.4% [67.5%‐79.3%] respectively. APOE‐ε4 status primarily modulated the association of age with tau‐PET‐positivity estimates among CN and MCI amyloid‐positive participants (Figure 2). Conclusion This large‐scale multi‐cohort study provides robust prevalence estimates of tau‐PET‐positivity, which can aid the interpretation of tau‐PET in the clinic and inform clinical trial designs.

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Journal
Alzheimer s & Dementia
Published
2024-12-01
DOI
https://doi.org/10.1002/alz.088686
Citations
1
Primary Topic
Alzheimer's disease research and treatments
Type
article
Field-Weighted Citation Impact
0.33
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article

The prevalence of tau‐PET positivity in aging and dementia

Tammie L.S. Benzinger, Vincent Doré, Reisa Anne Sperling, Gérard N. Bischof et al.
1 citations
Alzheimer s & Dementia
Alzheimer's disease research and treatments
0.33
article

The prevalence of tau‐PET positivity in aging and dementia

Tammie L.S. Benzinger, Vincent Doré, Reisa Anne Sperling, Gérard N. Bischof, Maura Malpetti, Jun Pyo Kim, Joseph Therriault, Tobey J. Betthauser, Bradley Christian, John T. O’Brien, Judes Poirier, Michael Rullmann, Renaud La Joie, Michel Bottlaender, Yuna Gu, Julien Lagarde, Shannon L. Risacher, Sebastian Palmqvist, Rik Ossenkoppele, Erik Stomrud, James B. Rowe, Andrew J. Saykin, María C. Carrillo, Pieter Jelle Visser, Olof T. Strandberg, Wiesje M. van der Flier, Marie Sarazin, Sergey Shcherbinin, Henryk Barthel, Emma M. Coomans, Valentina Garibotto, Elsmarieke van de Giessen, David M. Cash, Ruben Smith, Niklas Mattsson, Brad C. Dickerson, Nesrine Rahmouni, Oskar Hansson, Johannes Gnörich, Anouk den Braber, Gil Dan Rabinovici, Konstantin Messerschmidt, William Coath, Victor L. Villemagne, Ingmar Gr. Skoog, Ian Kennedy, Michael J. Pontecorvo, Suzanne L. Baker, Débora Elisa Peretti, Juan Domingo Gispert, Rik R. Vandenberghe, Michael Schöll, Keith A. Johnson, Elizabeth C. Mormino, Alexander Drzezga, Theresa M. Harrison, Silke Kern, Nicolai Franzmeier, Koen Van Laere, Sylvia Villeneuve, Christina B. Young, Carolina Minguillón, Pedro Rosa‐Neto, Hillary Vossler, Mahnaz Shekari, Colin Groot, Yolande A.L. Pijnenburg, Christopher C. Rowe, Sterling C. Johnson, Giovanni B. Frisoni, Howard J. Rosen, Liana G. Apostolova, Sang Won Seo, Elena Jäger, Matthias Brendel, William J. Jagust, Jonathan M. Schott, Laure Spruyt
article en
1 citations

Abstract

Abstract Background Tau‐PET imaging allows in‐vivo detection of neurofibrillary tangles. One tau‐PET tracer (i.e., [ 18 F]flortaucipir) has received FDA‐approval for clinical use, and multiple other tau‐PET tracers have been implemented into clinical trials for participant selection and/or as a primary or secondary outcome measure. To optimize future use of tau‐PET, it is essential to understand how demographic, clinical and genetic factors affect tau‐PET‐positivity rates. Method This large‐scale multi‐center study includes 9713 participants from 35 cohorts worldwide who underwent tau‐PET with [ 18 F]flortaucipir (n=6420), [ 18 F]RO948 (n=1999), [ 18 F]MK6240 (n=878) or [ 18 F]PI2620 (n=416) (Table 1). We analyzed individual‐level tau‐PET SUVR data using a cerebellar reference region that were processed either centrally (n=3855) or by each cohort (n=5858). We computed cohort‐specific SUVR thresholds based on the mean + 2 standard deviations in a temporal meta‐region of amyloid‐negative cognitively normal (CN) individuals aged >50. Logistic generalized estimating equations were used to estimate tau‐PET‐positivity probabilities, using an exchangeable correlation structure to account for within‐cohort correlations. Analyses were performed with (interactions between) age, amyloid‐status, and APOE‐ε4 carriership as independent variables, stratified for syndrome diagnosis. Result The study included 5962 CN participants (7.5% tau‐PET‐positive), 1683 participants with mild cognitive impairment (MCI, 33.8% tau‐PET‐positive) and 2068 participants with a clinical diagnosis of dementia (62.1% tau‐PET‐positive) (Figure 1). From age 60 to 80 years, the estimated prevalence of tau‐PET‐positivity increased from 1.2% [95% CI: 0.9%‐1.5%] to 3.7% [2.3%‐5.1%] among CN amyloid‐negative participants; and from 16.4% [10.8%‐22.1%] to 20.5% [18.8%‐22.2%] among CN amyloid‐positive participants. Among amyloid‐negative participants with MCI and dementia, from age 60 to 80 years, the estimated prevalence of tau‐PET‐positivity increased from 3.5% [1.6%‐5.3%] to 11.8% [7.1%‐16.5%] and from 12.6% [4.5%‐20.7%] to 15.9% [6.7%‐25.1%] respectively. In contrast, among amyloid‐positive participants with MCI and dementia, from age 60 to 80 years, the estimated prevalence of tau‐PET‐positivity decreased from 66.5% [57.0%‐76.0%] to 48.3% [42.9%‐53.8%] and from 92.3% [88.7%‐95.9%] to 73.4% [67.5%‐79.3%] respectively. APOE‐ε4 status primarily modulated the association of age with tau‐PET‐positivity estimates among CN and MCI amyloid‐positive participants (Figure 2). Conclusion This large‐scale multi‐cohort study provides robust prevalence estimates of tau‐PET‐positivity, which can aid the interpretation of tau‐PET in the clinic and inform clinical trial designs.

Alzheimer s & DementiaVol. 20(S2)
University of Geneva (CH), Alzheimer's Association (US), Centre National de la Recherche Scientifique (FR), University of Wisconsin–Madison (US), Harvard University (US), Lawrence Berkeley National Laboratory (US), Inserm (FR), The University of Melbourne (AU), Eli Lilly (United States) (US), University of Pittsburgh (US), University of California, San Francisco (US), University of Cologne (DE), Lund University (SE), Washington University in St. Louis (US), Université Paris Cité (FR), University of Cambridge (GB), Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR), Université Paris-Saclay (FR), Douglas Mental Health University Institute (CA), Samsung Medical Center (KR), Cambridge University Hospitals NHS Foundation Trust (GB), LMU Klinikum (DE), Maastricht University (NL), Massachusetts General Hospital (US), Mallinckrodt (United States) (US), University Hospital of Geneva (CH), Pasqual Maragall Foundation (ES), Amsterdam Neuroscience (NL), München Klinik (DE), Centre Hospitalier Sainte-Anne (FR), UK Dementia Research Institute (GB), Barcelonaβeta Brain Research Center (ES), CEA Paris-Saclay (FR), Skåne University Hospital (SE), National Hospital for Neurology and Neurosurgery (GB), Amsterdam University Medical Centers (NL), University Hospital Cologne (DE), Austin Health (AU), Indiana University School of Medicine, University College London (GB), McGill University (CA), Indiana University – Purdue University Indianapolis (US), Ludwig-Maximilians-Universität München (DE), Sungkyunkwan University (KR), Vrije Universiteit Amsterdam (NL), University of Gothenburg (SE), Leipzig University (DE), University of California, Berkeley (US), Stanford University (US), KU Leuven (BE)
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Alzheimer's disease research and treatments
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