Amyloid Load - a more sensitive biomarker for amyloid imaging.

Amyloid-β (Aβ) plays a key role in the pathogenesis of Alzheimer's disease (AD) and it can be imaged in vivo using [18 F]-AV45 positron emission tomography (PET). The mean cortical standardised uptake value ratio (SUVr) is a commonly used outcome measure for quantifying the global Aβ burden however the sensitivity is sub-optimal which can lead to low power in clinical trials. We introduce amyloid load, AβL as a novel biomarker to quantify the global Aβ burden along with an automated algorithm for its calculation (IQA ). AβL is evaluated on cross-sectional and longitudinal data obtained from the Alzheimer's disease neuroimaging initiative (ADNI). The cross-sectional data consisted of 769 subjects across the disease spectrum (211 healthy controls (HC), 223 early mild cognitive impairment (EMCI), 204 late mild cognitive impairment (LMCI), 132 AD). The distributions of in the four different classifications were compared and the same analyses were applied to the mean cortical SUVr outcome measure. The effect sizes (hedges' g) between all classifications were higher for AβL than mean cortical SUVr with the mean difference in effect size being 56%. 147 of the EMCI patients had a two-year follow-up scan and the effect size between baseline and follow-up for was 0.49 compared to 0.35 for mean cortical SUVr demonstrating an equivalent increase in power for longitudinal data. These results provide evidence that AβL will be a valuable outcome measure in future Aβ imaging studies providing an substantial increase in power over currently employed SUVr methods.