61 Grey zone amyloid burden Questionnaires Within the SCIENCe cohort, a number of questionnaires are administered to evaluate subjective cognitive complaints, mental health, instrumental activities of daily living, and lifestyle (27). For this study, we used the Cognitive Change Index (CCI, 20 questions, range 0 – 80) to quantify the degree of subjective cognitive complaints. We additionally used the Geriatric Depression Scale (GDS, 15 questions, range 0 – 15) to evaluate depressive symptoms. For both questionnaires a higher score reflects more severe symptoms. PET acquisition and image analysis PET scans were acquired on an Ingenuity PET-CT (n=115) or a Gemini TF PET-CT (n=47; Philips, Best, the Netherlands) scanner. Dynamic PET emission scans of 90 minutes (n=137) were obtained starting directly after tracer injection of approximately 370 mega Becquerel (MBq) [18F]florbetapir. During the course of the study, our group showed that the scan duration could be reduced without compromising the reliability of results (14). Therefore, the more recent scans (n=21) had a duration of 70 minutes. Furthermore, in four participants the scan was terminated early (three after 60 minutes, one after 79 minutes) due to participant related issues. These scans were still used since they had an uninterrupted 60 minutes of scanning (14). Head movement when lying in the camera was monitored with laser beams, and if necessary, the position of the head was corrected. Data were reconstructed with a standard LOR RAMLA reconstruction algorithm into 22 frames, and images were corrected for scatter, random coincidences, attenuation, decay and dead time. Images were reconstructed with a matrix size of 128 × 128 × 90 and a voxel size of 2 × 2 × 2 mm3. Isotropic 3-dimensional T1-weighted MR images (GE Discovery MR750 3T (n=58), PETMR 3T (n=71), Signa 1.5T (n=6), Signa 3T (n=2), Titan 3T (n=24) and external scan (n=1)) were co-registered to PET images using Vinci software (Max Planck Institute, Cologne, Germany). Regions of interest (ROIs) were defined on the co-registered MRI using the Hammers probability atlas (30) in PVElab. Receptor parametric mapping (RPM) was used to generate BPND images with cerebellar grey matter as a reference region (14, 16, 17, 31). We extracted BPND and SUVr50-70 values in the following a priori defined regions: orbitofrontal, temporal, parietal, anterior cingulate, posterior cingulate and precuneus (21). An SUVr time interval of 50-70 minutes post-injection was chosen because this is commonly used, and our group showed before that SUVr becomes constant from 40 minutes onward (14, 18). We subsequently averaged the values of the a priori defined regions into one volume weighted mean cortical BPND or SUVr value. The difference in time between MRI and PET was generally within one year (median time difference 0.22 years (IQR -0.49 – 0.55)). 3
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