Collij, Lyduine E.Salvadó, GemmaWottschel, ViktorMastenbroek, Sophie E.Schoenmakers, PierreHeeman, FionaAksman, LeonWink, Alle MeijeBerckel, Bart N.M.van de Flier, Wiesje M.Scheltens, PhilipVisser, Pieter JelleBarkhof, FrederikHaller, SvenGispert López, Juan DomingoLopes Alves, IsadoraAlzheimer’s Disease Neuroimaging InitiativeALFA Study2022-11-282022-11-282022Collij 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.00000000002001480028-3878http://hdl.handle.net/10230/55009Background 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.application/pdfengCopyright © 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.Alzheimer, Malaltia d'AmiloïdosiRessonància magnèticainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1212/WNL.0000000000200148info:eu-repo/semantics/openAccess