Stress testing the Centiloid: Precision and variability of PET quantification of amyloid pathology

Abstract

INTRODUCTION: Assessing the potential sources of bias and variability of the Centiloid (CL) scale is fundamental for its appropriate clinical application. // METHODS: We included 533 participants from AMYloid imaging to Prevent Alzheimer's Disease (AMYPAD DPMS) and Alzheimer's Disease Neuroimaging Initiative (ADNI) cohorts. Thirty-two CL pipelines were created using different combinations of reference region (RR), RR and target types, and quantification spaces. Generalized estimating equations stratified by amyloid positivity were used to assess the impact of the quantification pipeline, radiotracer, age, brain atrophy, and harmonization status on CL. // RESULTS: RR selection and RR type impact CL the most, particularly in amyloid-negative individuals. The standard CL pipeline with the whole cerebellum as RR is robust against brain atrophy and differences in image resolution, with 95% confidence intervals below ± 3.95 CL for amyloid beta positivity cutoffs (CL < 24). // DISCUSSION: The standard CL pipeline is recommended for most scenarios. Confidence intervals should be considered when operationalizing CL cutoffs in clinical and research settings