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

Ariane Bollack*, Lyduine E. Collij, David Vallez Garcia, Mahnaz Shekari, Daniele Altomare, Pierre Payoux, Bruno Dubois, Oriol Grau-Rivera, Merce Boada, Marta Marquie, Agneta Nordberg, Zuzana Walker, Philip Scheltens, Michael Scholl, Robin Wolz, Jonathan M. Schott, Rossella Gismondi, Andrew Stephens, Christopher Buckley, Giovanni B. FrisoniBernard Hanseeuw, Pieter Jelle Visser, Rik Vandenberghe, Alexander Drzezga, Maqsood Yaqub, Ronald Boellaard, Juan Domingo Gispert, Pawel Markiewicz, David M. Cash, Gill Farrar, Frederik Barkhof, Amyloid Imaging to Prevent Alzheimer’s disease Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 [ 18F]flutemetamol, [ 18F]florbetaben or [ 18F]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.

Original languageEnglish
Pages (from-to)3429-3441
Number of pages13
JournalAlzheimer's & Dementia
Volume20
Issue number5
Early online date1 Apr 2024
DOIs
Publication statusPublished - May 2024

Keywords

  • Alzheimer's
  • amyloid
  • Centiloid
  • longitudinal PET
  • quantification
  • reliable accumulation
  • WHITE-MATTER REFERENCE
  • ALZHEIMERS-DISEASE
  • IMAGING BIOMARKER
  • COGNITIVE DECLINE
  • BETA DEPOSITION
  • PET
  • THRESHOLD
  • SCALE

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