65 Grey zone amyloid burden We presented thresholds, frequency and kappa values in table 2. When we applied the different thresholds, the amyloid positivity rates ranged from 26 (16%) to 41 (25%) for BPND thresholds, and from 22 (14%) to 37 (23%) for SUVr thresholds. For BPND as well as SUVr, the low K-means threshold resulted in the highest percentage of A+ individuals, and the high K-means threshold in the lowest percentage of A+ individuals. The grey zone, operationalised as the range between the lowest and highest K-means thresholds, consisted of 9% of individuals for both BPND and SUVr. Cohen’s kappa showed that there was substantial concordance between visual assessment and each of the six thresholds. Upon visual inspection, concordance was highest for BPND thresholds, but confidence intervals overlapped. Table 1. Baseline demographics by amyloid status based on visual assessment Total N=162 Amyloid negative N=124 Amyloid positive N=38 Age, mean (SD) 64 (8) 63 (8) 68 (8)* Sex, n female (%) 63 (39%) 47 (38%) 16 (42%) Education, mean (SD)a 6 (1) 6 (1) 6 (1) APOE ε4 status, n carrier (%) 54 (36%) 31 (26%) 23 (68%)* CCI, mean (SD)a,b 21.8 (14.5) 21.4 (15.0) 23.0 (13.1) GDS, mean (SD)a,b 2.4 (2.0) 2.5 (2.1) 2.3 (1.9) MMSE, mean (SD)a,b 28.9 (1.2) 28.9 (1.2) 28.7 (1.2) RAVLT delayed, mean (SD)b 9.1 (3.0) 9.3 (3.0) 8.3 (3.2) Amyloid load (BPND), mean (SD) 0.16 (0.13) 0.11 (0.06) 0.33 (0.18)* Amyloid load (SUVr), mean (SD) 1.24 (0.18) 1.17 (0.08) 1.45 (0.26)* Amyloid status was determined by visual assessment of the [18F]florbetapir PET scan. Education is rated using the Dutch Verhage system (33). Amyloid load represents the volume-weighted mean cortical value in a composite region of a priori defined regions (orbitofrontal, temporal, parietal, anterior cingulate, posterior cingulate and precuneus), with cerebellar grey matter as reference region. CCI and GDS test scores were available for 159 and 96 participants respectively. CCI = cognitive change index, SCF = subjective cognitive functioning, GDS = geriatric depression scale, MMSE = mini-mental state examination, RAVLT = rey auditory verbal learning task, BPND = Binding potential, SUVr = standardized uptake value ratio. a Mann-Whitney U test. All other analyses were performed using t-test and Chi-square. b Score on concurrent test. * p<0.01 for difference between amyloid negative and positive individuals. 3
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