%0 Journal Article
%T Investigating reliable amyloid accumulation in Centiloids: Results from the AMYPAD Prognostic and Natural History Study.
%A Bollack A
%A Collij LE
%A García DV
%A Shekari M
%A Altomare D
%A Payoux P
%A Dubois B
%A Grau-Rivera O
%A Boada M
%A Marquié M
%A Nordberg A
%A Walker Z
%A Scheltens P
%A Schöll M
%A Wolz R
%A Schott JM
%A Gismondi R
%A Stephens A
%A Buckley C
%A Frisoni GB
%A Hanseeuw B
%A Visser PJ
%A Vandenberghe R
%A Drzezga A
%A Yaqub M
%A Boellaard R
%A Gispert JD
%A Markiewicz P
%A Cash DM
%A Farrar G
%A Barkhof F
%A  
%J Alzheimers Dement
%V 20
%N 5
%D 2024 May 4
%M 38574374
%F 16.655
%R 10.1002/alz.13761
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>Our results support a 12-20 CL window for inclusion into early secondary prevention studies. Reliable accumulation definition warrants further investigations.