18F-Flutemetamol amyloid-PET imaging

All participants underwent ¹⁸F-flutemetamol PET on a 16-slice Biograph PET/CT scanner (Siemens, Erlangen, Germany). The tracer was injected as a bolus in an antecubital vein (mean activity 150 MBq, SD 5 MBq, range 134–162 MBq). Scan acquisition started 90 min after tracer injection and lasted for 30 min [27, 40]. Prior to PET acquisition, a low-dose CT scan of the head was performed for attenuation correction. Random and scatter correction were applied. Data were recorded in list mode and reconstructed into six 5-min frames using ordered subsets expectation maximization (four iterations × 16 subsets). Processing of ¹⁸F-flutemetamol PET was done using SPM8 running on Matlab R2012b as described in detail elsewhere [27]. A standardized uptake value ratio image (SUVR) was calculated using participant-specific cerebellar grey matter as a reference region (grey matter threshold: 0.3). Mean ¹⁸F-flutemetamol SUVR values were calculated for a composite region (SUVR _comp), which consisted out of five bilateral cortical regions: frontal, parietal, anterior cingulate, precuneus-posterior cingulate and lateral temporal. These regions were derived from the Automated Anatomical Labeling (AAL) atlas [41] and intersected with the participant-specific grey matter, thresholded at 0.3. In a next step, SUVR _comp values were converted to Centiloids (CLs) [42] using as conversion formula CL = 127.6 × SUVR - 149. Low or absent amyloid burden was defined as CL ≤10 CL, intermediate amyloid burden as CL between 10 and 50 and high amyloid burden as CL ≥50 [43].

For whole-brain voxelwise analyses, ¹⁸F-flutemetamol SUVR images were smoothed with an isotropic Gaussian kernel of 8 ×8×8 mm³ FWHM.

Sixty-eight participants received ¹⁸F-flutemetamol PET prior to a major scanner upgrade (on 14/03/2012), while the remaining 112 received ¹⁸F-flutemetamol PET after the upgrade date. The scanner upgrade effect was included as a dummy variable in voxelwise statistical models.