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  • Ossenkoppele, RikVrije Universiteit Amsterdam,Skåne University Hospital (author)

Accuracy of Tau Positron Emission Tomography as a Prognostic Marker in Preclinical and Prodromal Alzheimer Disease : A Head-to-Head Comparison against Amyloid Positron Emission Tomography and Magnetic Resonance Imaging

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • American Medical Association (AMA),2021
  • 11 s.

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  • LIBRIS-ID:oai:lup.lub.lu.se:8e2b153c-6b47-4828-849f-4f0ca3d53ef8
  • https://lup.lub.lu.se/record/8e2b153c-6b47-4828-849f-4f0ca3d53ef8URI
  • https://doi.org/10.1001/jamaneurol.2021.1858DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

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  • Importance: Tau positron emission tomography (PET) tracers have proven useful for the differential diagnosis of dementia, but their utility for predicting cognitive change is unclear. Objective: To examine the prognostic accuracy of baseline fluorine 18 (18F)-flortaucipir and [18F]RO948 (tau) PET in individuals across the Alzheimer disease (AD) clinical spectrum and to perform a head-to-head comparison against established magnetic resonance imaging (MRI) and amyloid PET markers. Design, Setting, and Participants: This prognostic study collected data from 8 cohorts in South Korea, Sweden, and the US from June 1, 2014, to February 28, 2021, with a mean (SD) follow-up of 1.9 (0.8) years. A total of 1431 participants were recruited from memory clinics, clinical trials, or cohort studies; 673 were cognitively unimpaired (CU group; 253 [37.6%] positive for amyloid-β [Aβ]), 443 had mild cognitive impairment (MCI group; 271 [61.2%] positive for Aβ), and 315 had a clinical diagnosis of AD dementia (315 [100%] positive for Aβ). Exposures: [18F]Flortaucipir PET in the discovery cohort (n = 1135) or [18F]RO948 PET in the replication cohort (n = 296), T1-weighted MRI (n = 1431), and amyloid PET (n = 1329) at baseline and repeated Mini-Mental State Examination (MMSE) evaluation. Main Outcomes and Measures: Baseline [18F]flortaucipir/[18F]RO948 PET retention within a temporal region of interest, MRI-based AD-signature cortical thickness, and amyloid PET Centiloids were used to predict changes in MMSE using linear mixed-effects models adjusted for age, sex, education, and cohort. Mediation/interaction analyses tested whether associations between baseline tau PET and cognitive change were mediated by baseline MRI measures and whether age, sex, and APOE genotype modified these associations. Results: Among 1431 participants, the mean (SD) age was 71.2 (8.8) years; 751 (52.5%) were male. Findings for [18F]flortaucipir PET predicted longitudinal changes in MMSE, and effect sizes were stronger than for AD-signature cortical thickness and amyloid PET across all participants (R2, 0.35 [tau PET] vs 0.24 [MRI] vs 0.17 [amyloid PET]; P <.001, bootstrapped for difference) in the Aβ-positive MCI group (R2, 0.25 [tau PET] vs 0.15 [MRI] vs 0.07 [amyloid PET]; P <.001, bootstrapped for difference) and in the Aβ-positive CU group (R2, 0.16 [tau PET] vs 0.08 [MRI] vs 0.08 [amyloid PET]; P <.001, bootstrapped for difference). These findings were replicated in the [18F]RO948 PET cohort. MRI mediated the association between [18F]flortaucipir PET and MMSE in the groups with AD dementia (33.4% [95% CI, 15.5%-60.0%] of the total effect) and Aβ-positive MCI (13.6% [95% CI, 0.0%-28.0%] of the total effect), but not the Aβ-positive CU group (3.7% [95% CI, -17.5% to 39.0%]; P =.71). Age (t = -2.28; P =.02), but not sex (t = 0.92; P =.36) or APOE genotype (t = 1.06; P =.29) modified the association between baseline [18F]flortaucipir PET and cognitive change, such that older individuals showed faster cognitive decline at similar tau PET levels. Conclusions and Relevance: The findings of this prognostic study suggest that tau PET is a promising tool for predicting cognitive change that is superior to amyloid PET and MRI and may support the prognostic process in preclinical and prodromal stages of AD.

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  • Smith, RubenSkåne University Hospital (author)
  • Mattsson-Carlgren, NiklasLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Brain Injury After Cardiac Arrest,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Clinical Memory Research,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,Skåne University Hospital(Swepub:lu)med-nmn (author)
  • Groot, ColinVrije Universiteit Amsterdam (author)
  • Leuzy, AntoineSkåne University Hospital (author)
  • Strandberg, OlofSkåne University Hospital (author)
  • Palmqvist, SebastianSkåne University Hospital (author)
  • Olsson, TomasSkåne University Hospital(Swepub:lu)rafy-toh (author)
  • Jögi, JonasSkåne University Hospital(Swepub:lu)klin-jjo (author)
  • Stormrud, ErikSkåne University Hospital (author)
  • Cho, Hanna (author)
  • Ryu, Young Hoon (author)
  • Choi, Jae YongKorea Institute of Radiological & Medical Sciences (KIRAMS) (author)
  • Boxer, Adam L.University of California, San Francisco (author)
  • Gorno-Tempini, Maria L.University of California, San Francisco (author)
  • Miller, Bruce L.University of California, San Francisco (author)
  • Soleimani-Meigooni, DavidUniversity of California, San Francisco (author)
  • Iaccarino, LeonardoUniversity of California, San Francisco (author)
  • La Joie, RenaudUniversity of California, San Francisco (author)
  • Baker, SuzanneLawrence Berkeley National Laboratory (author)
  • Borroni, EdilioF. Hoffmann-La Roche AG (author)
  • Klein, GregoryF. Hoffmann-La Roche AG (author)
  • Pontecorvo, Michael J.Avid Radiopharmaceuticals, Inc (author)
  • Devous, Michael D.Avid Radiopharmaceuticals, Inc (author)
  • Jagust, William J.University of California, Berkeley,Lawrence Berkeley National Laboratory (author)
  • Lyoo, Chul Hyoung (author)
  • Rabinovici, Gil D.Lawrence Berkeley National Laboratory,University of California, San Francisco (author)
  • Hansson, OskarLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)mphy-ohn (author)
  • Vrije Universiteit AmsterdamSkåne University Hospital (creator_code:org_t)

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  • In:JAMA Neurology: American Medical Association (AMA)78:8, s. 961-9712168-6149

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