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

Journal article

Bollack, A., Collij, L., García, D., Shekari, M., Altomare, D., Payoux, P., Dubois, B., Grau-Rivera, O., Boada, M., Marquié, M., Nordberg, A., Walker, Z., Scheltens, P., Schöll, M., Wolz, R., Schott, J.M., Gismondi, R., Stephens, A., Buckley, C., Frisoni, G.B., Hanseeuw, B., Visser, P.J., Vandenberghe, R., Drzezga, A., Yaqub, M., Boellaard, R., Gispert, J., Markiewicz, P., Cash, D., Farrar, G., Barkhof, F. and AMYPAD consortium (2024). Investigating reliable amyloid accumulation in Centiloids: Results from the AMYPAD Prognostic and Natural History Study. Alzheimer's & Dementia. https://doi.org/10.1002/alz.13761
AuthorsBollack, A., Collij, L., García, D., Shekari, M., Altomare, D., Payoux, P., Dubois, B., Grau-Rivera, O., Boada, M., Marquié, M., Nordberg, A., Walker, Z., Scheltens, P., Schöll, M., Wolz, R., Schott, J.M., Gismondi, R., Stephens, A., Buckley, C., Frisoni, G.B., Hanseeuw, B., Visser, P.J., Vandenberghe, R., Drzezga, A., Yaqub, M., Boellaard, R., Gispert, J., Markiewicz, P., Cash, D., Farrar, G., Barkhof, F. and AMYPAD consortium
AbstractTo 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. 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 [ F]flutemetamol, [ F]florbetaben or [ F]florbetapir amyloid-PET were included. A normative strategy was used to define reliable accumulation by estimating the 95 percentile of longitudinal measurements in sub-populations (N  = 101/750, N  = 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. 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. Our results support a 12-20 CL window for inclusion into early secondary prevention studies. Reliable accumulation definition warrants further investigations. [Abstract copyright: © 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.]
Keywordsquantification; longitudinal PET; amyloid; Centiloid; reliable accumulation; Alzheimer's
Year2024
JournalAlzheimer's & Dementia
PublisherWiley
ISSN1552-5279
Digital Object Identifier (DOI)https://doi.org/10.1002/alz.13761
Web address (URL)https://alz-journals.onlinelibrary.wiley.com/journal/15525279
Funder/ClientEPSRC-funded UCL Centre for Doctoral Training in Intelligent, Integrated Imaging in Healthcare (i4health)
Department of Health's NIHR- funded Biomedical Research Centre at University College London
NIHR Biomedical Research Centre at UCLH
Alzheimer's Disease Data Initiative (ADDI)
GE HealthCare
Innovative Medicines Initiative 2
Publication dates
Online04 Apr 2024
Publication process dates
Accepted31 Jan 2024
Deposited03 May 2024
Publisher's version
License
File Access Level
Open
Licensehttp://creativecommons.org/licenses/by/4.0/
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