TY - JOUR
T1 - Investigating reliable amyloid accumulation in Centiloids
T2 - Results from the AMYPAD Prognostic and Natural History Study
AU - Bollack, Ariane
AU - Collij, Lyduine E.
AU - García, David V. llez
AU - Shekari, Mahnaz
AU - Altomare, Daniele
AU - Payoux, Pierre
AU - Dubois, Bruno
AU - Grau-Rivera, Oriol
AU - Boada, Mercè
AU - Marquié, Marta
AU - Nordberg, Agneta
AU - Walker, Zuzana
AU - Scheltens, Philip
AU - Schöll, Michael
AU - Wolz, Robin
AU - Schott, Jonathan M.
AU - Gismondi, Rossella
AU - Stephens, Andrew
AU - Buckley, Christopher
AU - Frisoni, Giovanni B.
AU - Hanseeuw, Bernard
AU - Visser, Pieter Jelle
AU - Vandenberghe, Rik
AU - Drzezga, Alexander
AU - Yaqub, Maqsood
AU - Boellaard, Ronald
AU - Gispert, Juan Domingo
AU - Markiewicz, Pawel
AU - Cash, David M.
AU - Farrar, Gill
AU - Barkhof, Frederik
N1 - Publisher Copyright:
© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
PY - 2024/5
Y1 - 2024/5
N2 - 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 95th percentile of longitudinal measurements in sub-populations (NPNHS = 101/750, NInsight46 = 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.
AB - 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 95th percentile of longitudinal measurements in sub-populations (NPNHS = 101/750, NInsight46 = 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.
KW - Alzheimer's
KW - Centiloid
KW - amyloid
KW - longitudinal PET
KW - quantification
KW - reliable accumulation
UR - https://www.scopus.com/pages/publications/85189955499
U2 - 10.1002/alz.13761
DO - 10.1002/alz.13761
M3 - Article
C2 - 38574374
SN - 1552-5260
VL - 20
SP - 3429
EP - 3441
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 5
ER -