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

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.