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Article Dans Une Revue Alzheimer's & Dementia : the Journal of the Alzheimer's Association Année : 2024

Investigating reliable amyloid accumulation in Centiloids: Results from the AMYPAD Prognostic and Natural History Study

1 CMIC - Centre for Medical Image Computing
2 UCL - University College of London [London]
3 Amsterdam UMC - Amsterdam University Medical Center
4 Lund University
5 VU University Medical Center [Amsterdam]
6 BBRC - Barcelonaβeta Brain Research Center
7 UPF - Universitat Pompeu Fabra [Barcelona]
8 UniBs - Università degli Studi di Brescia = University of Brescia
9 ToNIC - Toulouse NeuroImaging Center
10 Service de Médecine Nucléaire - Rangueil [CHU Toulouse]
11 CHU Pitié-Salpêtrière [AP-HP]
12 Pasqual Maragall Foundation
13 UIC - Universitat Internacional de Catalunya [Barcelona]
14 CIBERNED - Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas
15 Karolinska Institutet [Stockholm]
16 KUH - Karolinska University Hospital [Solna, Sweden]
17 Essex Partnership University NHS Foundation Trust [U.K.]
18 GU - Göteborgs Universitet = University of Gothenburg
19 Sahlgrenska University Hospital [Gothenburg]
20 UCL Queen Square Institute of Neurology
21 XICO Plc [ London, UK]
22 UCL Institute of Neurology, Queen Square [London]
23 Life Molecular Imaging [ Berlin, Germany]
24 GE Healthcare - General Electric Medical Systems [Buc]
25 Cliniques Universitaires Saint-Luc [Bruxelles]
26 UCL - Université Catholique de Louvain = Catholic University of Louvain
27 Massachusetts General Hospital [Boston]
28 WELBIO Department, WEL Research Institute, Avenue Pasteur, 6, 1300, Wavre
29 CCK - Cancer Center Karolinska [Karolinska Institutet]
30 MUMC - Maastricht University Medical Centre
31 LBI - Leuven Brain Institute [Leuven, Belgium]
32 Uniklinik Köln - Universitätsklinikum Köln
33 FZJ - Forschungszentrum Jülich GmbH | Centre de recherche de Jülich | Jülich Research Centre
34 Institute for Neuroscience and Medicine (INM-6)
35 DZNE - German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen
36 UMCG - University Medical Center Groningen [Groningen]
37 University of Groningen [Groningen]
38 ISC - Instituto de Salud Carlos III [Madrid]
39 LSBU - London South Bank University
40 UK DRI - UK Dementia Research Institute

Résumé

INTRODUCTION To support clinical trial designs focused on early interventions, our study determined reliable early amyloid‐β (Aβ) accumulation based on Centiloids (CL) in pre‐dementia populations. METHODS A total of 1032 participants from the Amyloid Imaging to Prevent Alzheimer's Disease–Prognostic and Natural History Study (AMYPAD‐PNHS) and Insight46 who underwent [ 18 F]flutemetamol, [ 18 F]florbetaben or [ 18 F]florbetapir amyloid‐PET were included. A normative strategy was used to define reliable accumulation by estimating the 95 th percentile of longitudinal measurements in sub‐populations ( N PNHS = 101/750, N Insight46 = 35/382) expected to remain stable over time. The baseline CL threshold that optimally predicts future accumulation was investigated using precision‐recall analyses. Accumulation rates were examined using linear mixed‐effect models. RESULTS Reliable accumulation in the PNHS was estimated to occur at >3.0 CL/year. Baseline CL of 16 [12,19] best predicted future Aβ‐accumulators. Rates of amyloid accumulation were tracer‐independent, lower for APOE ε4 non‐carriers, and for subjects with higher levels of education. DISCUSSION Our results support a 12–20 CL window for inclusion into early secondary prevention studies. Reliable accumulation definition warrants further investigations.
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hal-04620410 , version 1 (21-06-2024)

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Ariane Bollack, Lyduine E Collij, David Vállez García, Mahnaz Shekari, Daniele Altomare, et al.. Investigating reliable amyloid accumulation in Centiloids: Results from the AMYPAD Prognostic and Natural History Study. Alzheimer's & Dementia : the Journal of the Alzheimer's Association, 2024, 20 (5), pp.3429-3441. ⟨10.1002/alz.13761⟩. ⟨hal-04620410⟩
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