{Reference Type}: Journal Article
{Title}: Investigating reliable amyloid accumulation in Centiloids: Results from the AMYPAD Prognostic and Natural History Study.
{Author}: 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;Barkhof F; ;
{Journal}: Alzheimers Dement
{Volume}: 20
{Issue}: 5
{Year}: 2024 May 4
{Factor}: 16.655
{DOI}: 10.1002/alz.13761
{Abstract}: <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.