1. Investigating reliable amyloid accumulation in Centiloids: Results from the AMYPAD Prognostic and Natural History Study.
- Author
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Bollack A, Collij LE, García DV, 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 JM, Gismondi R, Stephens A, Buckley C, Frisoni GB, Hanseeuw B, Visser PJ, Vandenberghe R, Drzezga A, Yaqub M, Boellaard R, Gispert JD, Markiewicz P, Cash DM, Farrar G, and Barkhof F
- Subjects
- Humans, Male, Female, Aged, Prognosis, Middle Aged, Longitudinal Studies, Stilbenes, Brain diagnostic imaging, Brain metabolism, Benzothiazoles, Positron-Emission Tomography, Amyloid beta-Peptides metabolism, Alzheimer Disease diagnostic imaging, Alzheimer Disease metabolism, Aniline Compounds
- 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 [
18 F]flutemetamol, [18 F]florbetaben or [18 F]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., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)- Published
- 2024
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