59 Grey zone amyloid burden INTRODUCTION The presence of pathological amyloid beta depositions is one of the hallmarks of Alzheimer’s disease (AD) and amyloid pathology is thought to play an important role in its pathophysiology (1, 2). Indeed, high amyloid burden in cognitively normal individuals is associated with a greater risk of cognitive decline, particularly of memory function (3-9). Furthermore, individuals with subjective cognitive decline (SCD) are more often amyloid positive than the general population and are at increased risk of cognitive decline and dementia (10, 11). Therefore, individuals with SCD form an ideal population to study the effects of ’early’ amyloid deposition on cognition. Amyloid beta pathology can be assessed in vivo by [18F]florbetapir Positron Emission Tomography (PET) using visual assessment in a dichotomous manner, i.e. positive vs negative (12). However, the accuracy depends on the expertise of the trained reader (13), and visual assessment of scans with early amyloid accumulation can be challenging. Classification of amyloid positivity can also be determined using a threshold as an alternative to visual assessment. The standardized uptake value ratio (SUVr) is a widely used method for estimating amyloid burden semi-quantitatively using a static scan procedure. Dynamic scanning allows for calculation of binding potential (BPND) which provides a more exact quantification of specific binding to amyloid beta (14). BPND has been shown to be less prone to overestimation compared to SUVr and is more reliable when studying early amyloid accumulation (15-17). So far, different SUVr thresholds for [18F]florbetapir have been proposed (18-23), but these thresholds are highly variable (range SUVr thresholds 1.08-1.34). BPND thresholds have not been published yet. Dichotomizing amyloid burden into a negative and positive status can be useful in clinical and research settings, but it disregards the potential significance of early (pathological) amyloid accumulation (24). Recent studies show that even in individuals that are initially labelled as amyloid negative, the amyloid accumulation slope is associated with memory decline (25, 26). It is uncertain whether this suggests that current thresholds are simply too high and lower thresholds would be able to correctly classify individuals, or that there is a more gradual association between memory decline and amyloid burden. The latter would point towards a ‘dose-dependent risk’ with a grey zone amyloid burden reflecting an at risk state for AD. In the current study, we aimed to define thresholds for amyloid positivity using datadriven methods based on both SUVr and BPND. Subsequently, we compared each of these classifications to visual assessment of amyloid positivity and determined 3