Spatial-temporal patterns of β-amyloid accumulation: a subtype and stage inference model analysis

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Collij, Lyduine E.
• dc.contributor.author Salvadó, Gemma
• dc.contributor.author Wottschel, Viktor
• dc.contributor.author Mastenbroek, Sophie E.
• dc.contributor.author Schoenmakers, Pierre
• dc.contributor.author Heeman, Fiona
• dc.contributor.author Aksman, Leon
• dc.contributor.author Wink, Alle Meije
• dc.contributor.author Berckel, Bart N.M.
• dc.contributor.author van de Flier, Wiesje M.
• dc.contributor.author Scheltens, Philip
• dc.contributor.author Visser, Pieter Jelle
• dc.contributor.author Barkhof, Frederik
• dc.contributor.author Haller, Sven
• dc.contributor.author Gispert López, Juan Domingo
• dc.contributor.author Lopes Alves, Isadora
• dc.contributor.author Alzheimer’s Disease Neuroimaging Initiative
• dc.contributor.author ALFA Study
• dc.date.accessioned 2022-11-28T07:57:23Z
• dc.date.available 2022-11-28T07:57:23Z
• dc.date.issued 2022
• dc.description.abstract Background and objectives: β-amyloid (Aβ) staging models assume a single spatial-temporal progression of amyloid accumulation. We assessed evidence for Aβ accumulation subtypes by applying the data-driven Subtype and Stage Inference (SuStaIn) model to amyloid-PET data. Methods: amyloid-PET data of 3,010 participants were pooled from 6 cohorts (ALFA+, EMIF-AD, ABIDE, OASIS, and ADNI). Standardized uptake value ratios were calculated for 17 regions. We applied the SuStaIn algorithm to identify consistent subtypes in the pooled dataset based on the cross-validation information criterion and the most probable subtype/stage classification per scan. The effects of demographics and risk factors on subtype assignment were assessed using multinomial logistic regression. Results: participants were mostly cognitively unimpaired (n = 1890 [62.8%]), had a mean age of 68.72 (SD 9.1) years, 42.1% were APOE ε4 carriers, and 51.8% were female. A 1-subtype model recovered the traditional amyloid accumulation trajectory, but SuStaIn identified 3 optimal subtypes, referred to as frontal, parietal, and occipital based on the first regions to show abnormality. Of the 788 (26.2%) with strong subtype assignment (>50% probability), the majority was assigned to frontal (n = 415 [52.5%]), followed by parietal (n = 199 [25.3%]) and occipital subtypes (n = 175 [22.2%]). Significant differences across subtypes included distinct proportions of APOE ε4 carriers (frontal 61.8%, parietal 57.1%, occipital 49.4%), participants with dementia (frontal 19.7%, parietal 19.1%, occipital 31.0%), and lower age for the parietal subtype (frontal/occipital 72.1 years, parietal 69.3 years). Higher amyloid (Centiloid) and CSF p-tau burden was observed for the frontal subtype; parietal and occipital subtypes did not differ. At follow-up, most participants (81.1%) maintained baseline subtype assignment and 25.6% progressed to a later stage. Discussion: whereas a 1-trajectory model recovers the established pattern of amyloid accumulation, SuStaIn determined that 3 subtypes were optimal, showing distinct associations with Alzheimer disease risk factors. Further analyses to determine clinical utility are warranted.
• dc.description.sponsorship The project leading to this article has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement 115952. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. This communication reflects the views of the authors and neither the Innovative Medicines Initiative nor the European Union or EFPIA are liable for any use of the information contained herein. The ALFA study received funding from “la Caixa” Foundation (ID 100010434) under agreement LCF/PR/GN17/50300004, the Alzheimer's Association, and an international anonymous charity foundation through the TriBEKa Imaging Platform project (TriBEKa-17-519007). Additional support has been received from the Universities and Research Secretariat, Ministry of Business and Knowledge of the Catalan Government under grant 2017-SGR-892. J.D.G. is supported by the Spanish Ministry of Science and Innovation (RYC-2013-13054) and the Agencia Estatal de Investigación Proyectos de I+D+i Retos Investigación (RTI2018-102261-B-I00).
• dc.format.mimetype application/pdf
• dc.identifier.citation Collij LE, Salvadó G, Wottschel V, Mastenbroek SE, Schoenmakers P, Heeman F, et al. Spatial-temporal patterns of β-amyloid accumulation: a subtype and stage inference model analysis. Neurology. 2022 Apr 26; 98(17): e1692-703. DOI: 10.1212/WNL.0000000000200148
• dc.identifier.doi http://dx.doi.org/10.1212/WNL.0000000000200148
• dc.identifier.issn 0028-3878
• dc.identifier.uri http://hdl.handle.net/10230/55009
• dc.language.iso eng
• dc.publisher Lippincott Williams & Wilkins
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/ 666992
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/115952
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-102261
• dc.rights Copyright © 2022. Collij LE, Salvadó G, Wottschel V, Mastenbroek SE, Schoenmakers P, Heeman F, et al. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), http://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.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.other Alzheimer, Malaltia d'
• dc.subject.other Amiloïdosi
• dc.subject.other Ressonància magnètica
• dc.title Spatial-temporal patterns of β-amyloid accumulation: a subtype and stage inference model analysis
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion