Pittsburgh Compound B (PiB) Positron Emission Tomography (PET) neuroimaging is a powerful research tool to characterize amyloid evolution in the brain of normal aging and people affected with Alzheimer`s Disease or its prodromal states. Quantification of amyloid load critically depends on the choice of a reference region (RR) with low levels of amyloid and low variability; and on the selection of regions of interest (ROI) to derive the standard uptake value ratios (SUVRs). We used imaging data from the Alzheimer`s Disease Neuroimaging Initiative cohort to evaluate the stability, i.e. negligible amyloid accumulation over time, of different RRs to yield an ROI composite that maximizes the ability to detect longitudinal change in amyloid burden in patients with Mild Cognitively Impairment (MCI) and Alzheimer`s Disease (AD). Standardized uptake value ratios (SUVRs), normalized to cerebellar grey matter were renormalized to alternative RRs - sub-cortical white matter and pons. We then performed cross-sectional and longitudinal analyses of focal regional and composite measures of amyloid accumulation. Further, we evaluated RRs and candidate composite SUVR measures to select regions and develop novel composite. Sample size calculations were carried out to compare novel and conventional composites.