Stress testing the Centiloid: Precision and variability of PET quantification of amyloid pathology

Shekari, Mahnaz; Vállez García, David; Collij, Lyduine E.; Altomare, Daniele; Heeman, Fiona; Pemberton, Hugh G.; Roé Vellvé, Núria; Bullich, Santiago; Buckley, Christopher, 1948-; Stephens, Andrew W.; Farrar, Gill; Frisoni, Giovanni B.; Klunk, William E.; Barkhof, Frederik; Gispert López, Juan Domingo; ADNI; AMYPAD Consortium; Context of use; Diagnosis; Disease‐modifying therapies; Image harmonization; Radiotracers; White matter

Stress testing the Centiloid: Precision and variability of PET quantification of amyloid pathology

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dc.contributor.author Shekari, Mahnaz
dc.contributor.author Vállez García, David
dc.contributor.author Collij, Lyduine E.
dc.contributor.author Altomare, Daniele
dc.contributor.author Heeman, Fiona
dc.contributor.author Pemberton, Hugh G.
dc.contributor.author Roé Vellvé, Núria
dc.contributor.author Bullich, Santiago
dc.contributor.author Buckley, Christopher, 1948-
dc.contributor.author Stephens, Andrew W.
dc.contributor.author Farrar, Gill
dc.contributor.author Frisoni, Giovanni B.
dc.contributor.author Klunk, William E.
dc.contributor.author Barkhof, Frederik
dc.contributor.author Gispert López, Juan Domingo
dc.contributor.author ADNI
dc.contributor.author AMYPAD Consortium
dc.contributor.author Context of use
dc.contributor.author Diagnosis
dc.contributor.author Disease‐modifying therapies
dc.contributor.author Image harmonization
dc.contributor.author Radiotracers
dc.contributor.author White matter
dc.date.accessioned 2025-02-18T06:16:56Z
dc.date.available 2025-02-18T06:16:56Z
dc.date.issued 2024
dc.description.abstract Introduction: Assessing the potential sources of bias and variability of the Centiloid (CL) scale is fundamental for its appropriate clinical application. Methods: We included 533 participants from AMYloid imaging to Prevent Alzheimer's Disease (AMYPAD DPMS) and Alzheimer's Disease Neuroimaging Initiative (ADNI) cohorts. Thirty-two CL pipelines were created using different combinations of reference region (RR), RR and target types, and quantification spaces. Generalized estimating equations stratified by amyloid positivity were used to assess the impact of the quantification pipeline, radiotracer, age, brain atrophy, and harmonization status on CL. Results: RR selection and RR type impact CL the most, particularly in amyloid-negative individuals. The standard CL pipeline with the whole cerebellum as RR is robust against brain atrophy and differences in image resolution, with 95% confidence intervals below ± 3.95 CL for amyloid beta positivity cutoffs (CL < 24). Discussion: The standard CL pipeline is recommended for most scenarios. Confidence intervals should be considered when operationalizing CL cutoffs in clinical and research settings. Highlights: We developed a framework for evaluating Centiloid (CL) variability to different factors. Reference region selection and delineation had the highest impact on CL values. Whole cerebellum (WCB) and whole cerebellum plus brainstem (WCB+BSTM) as reference regions yielded consistent results across tracers. The standard CL pipeline is robust against atrophy and image resolution variation. Estimated within- and between-pipeline variability (95% confidence interval) in absolute CL units.
dc.description.sponsorship The authors acknowledge all data donors and collaborators involved in AMYPAD and Alzheimer's Disease Neuroimaging Initiative (ADNI) studies. This research would not have been possible without the time and dedication of every participant included in these studies. “AMYPAD project leading to this application has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 115952. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and EFPIA.” This communication reflects the views of the authors and neither the Innovative Medicines Initiative (IMI) nor the European Union and EFPIA are liable for any use that may be made of the information contained herein.
dc.format.mimetype application/pdf
dc.identifier.citation Shekari M, Vállez García D, Collij LE, Altomare D, Heeman F, Pemberton H, et al. Stress testing the Centiloid: Precision and variability of PET quantification of amyloid pathology. Alzheimers Dement. 2024 Aug;20(8):5102-13. DOI: 10.1002/alz.13883
dc.identifier.doi http://dx.doi.org/10.1002/alz.13883
dc.identifier.issn 1552-5260
dc.identifier.uri http://hdl.handle.net/10230/69623
dc.language.iso eng
dc.publisher Wiley
dc.relation.ispartof Alzheimers Dement. 2024 Aug;20(8):5102-13
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/115952
dc.rights © The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword Alzheimer's disease
dc.subject.keyword Age
dc.subject.keyword Amyloid PET accuracy
dc.subject.keyword Biomarker validation
dc.subject.keyword Brain atrophy
dc.subject.keyword Clinical applications
dc.subject.keyword Clinical trials
dc.title Stress testing the Centiloid: Precision and variability of PET quantification of amyloid pathology
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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