Authors: Jarith L. Ebenau, Sander C.J. Verfaillie, Karlijn A. van den Bosch, Tessa Timmers, Linda M.P. Wesselman, Mardou van Leeuwenstijn, Frederik Barkhof, Niels D. Prins, Philip Scheltens, Wiesje van Der Flier, Bart N.M. Van Berckel
Published: 2020-12-07
DOI: 10.1002/alz.045210
Source: Full article
AbstractBackgroundWe aimed to compare different thresholds for amyloid‐beta pathology and their associations with memory decline, and to investigate the clinical significance of ‘grey zone’ amyloid‐beta burden in cognitively normal individuals.MethodWe included 162 cognitively normal participants with subjective cognitive decline (SCD) from the SCIENCe cohort (64±8yr, 38%F, MMSE 29±1). Each underwent a 70‐minutes dynamic [18F]florbetapir PET, T1‐weighted MRI and longitudinal neuropsychological assessment (n=149≥2 visits). PET scans were classified as positive/negative for amyloid pathology by visual assessment (VA). We calculated a mean binding potential (BPND) and mean standardized uptake value ratio (SUVr50‐70) for a composite region of interest (orbitofrontal, temporal, anterior/posterior cingulate, precuneus). Using Gaussian mixture modelling and k‐means clustering (2 clusters: 90% of low cluster, 10% of high cluster), we derived 3 thresholds for amyloid positivity (A+) based on both BPND and SUVr. We compared associations with memory decline for each threshold using linear mixed models (LMM). To investigate whether grey zone amyloid burden is clinically meaningful, we divided the sample into quantiles, and additionally predefined a grey zone using K‐means thresholds (K‐low/K‐grey/K‐high).ResultThe low K‐means thresholds (BPND=0.18, SUVr=1.27) were most comparable to VA (specificity 76% and 71%, Table 1). LMM showed that all A+ thresholds had comparable associations with rate of memory decline to VA (range β ‐0.39 − ‐0.48). With increasing quantile‐levels, memory slopes gradually became steeper for both BPND and SUVr. The predefined grey zone (BPND 0.18‐0.27, SUVr 1.27‐1.42) was significantly associated with memory decline for both BPND (β ‐0.29(SE 0.14)) and SUVr (β ‐0.43 (SE 0.14)).ConclusionWe showed that amyloid positivity thresholds for BPND and SUVr are similar to visual assessment in their association with memory decline. Furthermore, the association between A+ and memory decline is not only driven by individuals with the highest amyloid values, but individuals with grey zone amyloid burden are also at risk of steeper memory decline. Therefore, in case a binary classification is required, we suggest using a relatively low threshold, e.g. BPND 0.18, which includes the grey zone.