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Derivation and utility of an Aβ-PET pathology accumulation index to estimate Aβ load

OBJECTIVE: To evaluate a novel β-amyloid (Aβ)-PET–based quantitative measure (Aβ accumulation index [Aβ index]), including the assessment of its ability to discriminate between participants based on Aβ status using visual read, CSF Aβ(42)/Aβ(40), and post-mortem neuritic plaque burden as standards o...

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Autores principales: Leuzy, Antoine, Lilja, Johan, Buckley, Christopher J., Ossenkoppele, Rik, Palmqvist, Sebastian, Battle, Mark, Farrar, Gill, Thal, Dietmar R., Janelidze, Shorena, Stomrud, Erik, Strandberg, Olof, Smith, Ruben, Hansson, Oskar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734735/
https://www.ncbi.nlm.nih.gov/pubmed/33077542
http://dx.doi.org/10.1212/WNL.0000000000011031
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author Leuzy, Antoine
Lilja, Johan
Buckley, Christopher J.
Ossenkoppele, Rik
Palmqvist, Sebastian
Battle, Mark
Farrar, Gill
Thal, Dietmar R.
Janelidze, Shorena
Stomrud, Erik
Strandberg, Olof
Smith, Ruben
Hansson, Oskar
author_facet Leuzy, Antoine
Lilja, Johan
Buckley, Christopher J.
Ossenkoppele, Rik
Palmqvist, Sebastian
Battle, Mark
Farrar, Gill
Thal, Dietmar R.
Janelidze, Shorena
Stomrud, Erik
Strandberg, Olof
Smith, Ruben
Hansson, Oskar
author_sort Leuzy, Antoine
collection PubMed
description OBJECTIVE: To evaluate a novel β-amyloid (Aβ)-PET–based quantitative measure (Aβ accumulation index [Aβ index]), including the assessment of its ability to discriminate between participants based on Aβ status using visual read, CSF Aβ(42)/Aβ(40), and post-mortem neuritic plaque burden as standards of truth. METHODS: One thousand one hundred twenty-one participants (with and without cognitive impairment) were scanned with Aβ-PET: Swedish BioFINDER, n = 392, [(18)F]flutemetamol; Alzheimer’s Disease Neuroimaging Initiative (ADNI), n = 692, [(18)F]florbetapir; and a phase 3 end-of-life study, n = 100, [(18)F]flutemetamol. The relationships between Aβ index and standardized uptake values ratios (SUVR) from Aβ-PET were assessed. The diagnostic performances of Aβ index and SUVR were compared with visual reads, CSF Aβ(42)/Aβ(40), and Aβ histopathology used as reference standards. RESULTS: Strong associations were observed between Aβ index and SUVR (R(2): BioFINDER 0.951, ADNI 0.943, end-of-life, 0.916). Both measures performed equally well in differentiating Aβ-positive from Aβ-negative participants, with areas under the curve (AUCs) of 0.979 to 0.991 to detect abnormal visual reads, AUCs of 0.961 to 0.966 to detect abnormal CSF Aβ(42)/Aβ(40), and AUCs of 0.820 to 0.823 to detect abnormal Aβ histopathology. Both measures also showed a similar distribution across postmortem-based Aβ phases (based on anti-Aβ 4G8 antibodies). Compared to models using visual read alone, the addition of the Aβ index resulted in a significant increase in AUC and a decrease in Akaike information criterion to detect abnormal Aβ histopathology. CONCLUSION: The proposed Aβ index showed a tight association to SUVR and carries an advantage over the latter in that it does not require the definition of regions of interest or the use of MRI. Aβ index may thus prove simpler to implement in clinical settings and may also facilitate the comparison of findings using different Aβ-PET tracers. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the Aβ accumulation index accurately differentiates Aβ-positive from Aβ-negative participants compared to Aβ-PET visual reads, CSF Aβ(42)/Aβ(40), and Aβ histopathology.
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spelling pubmed-77347352020-12-14 Derivation and utility of an Aβ-PET pathology accumulation index to estimate Aβ load Leuzy, Antoine Lilja, Johan Buckley, Christopher J. Ossenkoppele, Rik Palmqvist, Sebastian Battle, Mark Farrar, Gill Thal, Dietmar R. Janelidze, Shorena Stomrud, Erik Strandberg, Olof Smith, Ruben Hansson, Oskar Neurology Article OBJECTIVE: To evaluate a novel β-amyloid (Aβ)-PET–based quantitative measure (Aβ accumulation index [Aβ index]), including the assessment of its ability to discriminate between participants based on Aβ status using visual read, CSF Aβ(42)/Aβ(40), and post-mortem neuritic plaque burden as standards of truth. METHODS: One thousand one hundred twenty-one participants (with and without cognitive impairment) were scanned with Aβ-PET: Swedish BioFINDER, n = 392, [(18)F]flutemetamol; Alzheimer’s Disease Neuroimaging Initiative (ADNI), n = 692, [(18)F]florbetapir; and a phase 3 end-of-life study, n = 100, [(18)F]flutemetamol. The relationships between Aβ index and standardized uptake values ratios (SUVR) from Aβ-PET were assessed. The diagnostic performances of Aβ index and SUVR were compared with visual reads, CSF Aβ(42)/Aβ(40), and Aβ histopathology used as reference standards. RESULTS: Strong associations were observed between Aβ index and SUVR (R(2): BioFINDER 0.951, ADNI 0.943, end-of-life, 0.916). Both measures performed equally well in differentiating Aβ-positive from Aβ-negative participants, with areas under the curve (AUCs) of 0.979 to 0.991 to detect abnormal visual reads, AUCs of 0.961 to 0.966 to detect abnormal CSF Aβ(42)/Aβ(40), and AUCs of 0.820 to 0.823 to detect abnormal Aβ histopathology. Both measures also showed a similar distribution across postmortem-based Aβ phases (based on anti-Aβ 4G8 antibodies). Compared to models using visual read alone, the addition of the Aβ index resulted in a significant increase in AUC and a decrease in Akaike information criterion to detect abnormal Aβ histopathology. CONCLUSION: The proposed Aβ index showed a tight association to SUVR and carries an advantage over the latter in that it does not require the definition of regions of interest or the use of MRI. Aβ index may thus prove simpler to implement in clinical settings and may also facilitate the comparison of findings using different Aβ-PET tracers. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the Aβ accumulation index accurately differentiates Aβ-positive from Aβ-negative participants compared to Aβ-PET visual reads, CSF Aβ(42)/Aβ(40), and Aβ histopathology. Lippincott Williams & Wilkins 2020-11-24 /pmc/articles/PMC7734735/ /pubmed/33077542 http://dx.doi.org/10.1212/WNL.0000000000011031 Text en Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Article
Leuzy, Antoine
Lilja, Johan
Buckley, Christopher J.
Ossenkoppele, Rik
Palmqvist, Sebastian
Battle, Mark
Farrar, Gill
Thal, Dietmar R.
Janelidze, Shorena
Stomrud, Erik
Strandberg, Olof
Smith, Ruben
Hansson, Oskar
Derivation and utility of an Aβ-PET pathology accumulation index to estimate Aβ load
title Derivation and utility of an Aβ-PET pathology accumulation index to estimate Aβ load
title_full Derivation and utility of an Aβ-PET pathology accumulation index to estimate Aβ load
title_fullStr Derivation and utility of an Aβ-PET pathology accumulation index to estimate Aβ load
title_full_unstemmed Derivation and utility of an Aβ-PET pathology accumulation index to estimate Aβ load
title_short Derivation and utility of an Aβ-PET pathology accumulation index to estimate Aβ load
title_sort derivation and utility of an aβ-pet pathology accumulation index to estimate aβ load
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734735/
https://www.ncbi.nlm.nih.gov/pubmed/33077542
http://dx.doi.org/10.1212/WNL.0000000000011031
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