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.
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 [18F]flutemetamol, [18F]florbetaben or [18F]florbetapir amyloid-PET were included. A normative strategy was used to define reliable accumulation by estimating the 95th 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.
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.

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This post is Copyright: Ariane Bollack,
Lyduine E. Collij,
David Vállez García,
Mahnaz Shekari,
Daniele Altomare,
Pierre Payoux,
Bruno Dubois,
Oriol Grau‐Rivera,
Mercè Boada,
Marta Marquié,
Agneta Nordberg,
Zuzana Walker,
Philip Scheltens,
Michael Schöll,
Robin Wolz,
Jonathan M. Schott,
Rossella Gismondi,
Andrew Stephens,
Christopher Buckley,
Giovanni B. Frisoni,
Bernard Hanseeuw,
Pieter Jelle Visser,
Rik Vandenberghe,
Alexander Drzezga,
Maqsood Yaqub,
Ronald Boellaard,
Juan Domingo Gispert,
Pawel Markiewicz,
David M. Cash,
Gill Farrar,
Frederik Barkhof,
AMYPAD consortium | April 5, 2024

Wiley: Alzheimer’s & Dementia: Table of Contents