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

Bollack, Ariane ; Collij, Lyduine E. LU ; Garcia, David Vallez ; Shekari, Mahnaz ; Altomare, Daniele ; Payoux, Pierre ; Dubois, Bruno ; Grau-Rivera, Oriol ; Boada, Mercè and Marquié, Marta , et al. (2024) In Alzheimer's and Dementia 20(5). p.3429-3441
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 95th percentile of longitudinal measurements in sub-populations (NPNHS = 101/750, NInsight46 = 35/382) expected to remain stable over time. The... (More)

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.

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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's, amyloid, Centiloid, longitudinal PET, quantification, reliable accumulation
in
Alzheimer's and Dementia
volume
20
issue
5
pages
13 pages
publisher
Wiley
external identifiers
  • scopus:85189955499
  • pmid:38574374
ISSN
1552-5260
DOI
10.1002/alz.13761
language
English
LU publication?
yes
id
8736c089-1cde-4aa6-af16-eaaa3c3c4449
date added to LUP
2024-04-25 14:59:19
date last changed
2024-12-21 15:26:26
@article{8736c089-1cde-4aa6-af16-eaaa3c3c4449,
  abstract     = {{<p>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 [<sup>18</sup>F]flutemetamol, [<sup>18</sup>F]florbetaben or [<sup>18</sup>F]florbetapir amyloid-PET were included. A normative strategy was used to define reliable accumulation by estimating the 95<sup>th</sup> percentile of longitudinal measurements in sub-populations (N<sub>PNHS</sub> = 101/750, N<sub>Insight46</sub> = 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 &gt;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.</p>}},
  author       = {{Bollack, Ariane and Collij, Lyduine E. and Garcia, David Vallez and Shekari, Mahnaz and Altomare, Daniele and Payoux, Pierre and Dubois, Bruno and Grau-Rivera, Oriol and Boada, Mercè and Marquié, Marta and Nordberg, Agneta and Walker, Zuzana and Scheltens, Philip and Schöll, Michael and Wolz, Robin and Schott, Jonathan M. and Gismondi, Rossella and Stephens, Andrew and Buckley, Christopher and Frisoni, Giovanni B. and Hanseeuw, Bernard and Visser, Pieter Jelle and Vandenberghe, Rik and Drzezga, Alexander and Yaqub, Maqsood and Boellaard, Ronald and Gispert, Juan Domingo and Markiewicz, Pawel and Cash, David M. and Farrar, Gill and Barkhof, Frederik}},
  issn         = {{1552-5260}},
  keywords     = {{Alzheimer's; amyloid; Centiloid; longitudinal PET; quantification; reliable accumulation}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{3429--3441}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's and Dementia}},
  title        = {{Investigating reliable amyloid accumulation in Centiloids : Results from the AMYPAD Prognostic and Natural History Study}},
  url          = {{http://dx.doi.org/10.1002/alz.13761}},
  doi          = {{10.1002/alz.13761}},
  volume       = {{20}},
  year         = {{2024}},
}