MRI was performed at 3T with a 3D-MPRAGE sequence [9 (link)] Images were corrected for distortion due to gradient non-linearity and for bias field [10 (link), 11 ]. Our primary MRI measure was hippocampal volume measured with FreeSurfer software (version 4.5.0) [12 (link)]. Each subject’s raw hippocampal volume was adjusted by his/her total intracranial volume [13 (link)] to form an adjusted hippocampal volume (HVa). We calculated HVa as the residual from a linear regression of hippocampal volume (y) versus total intracranial volume (x).
PET images [14 (link)] were acquired using a PET/CT scanner. The 11C PIB-PET scan consisting of four 5-minute dynamic frames was acquired from 40–60 minutes after injection [15 (link), 16 (link)]. 18 Fluorodeoxyglucose (18F-FDG ) PET images were obtained 1 hour after the PIB scan. Subjects were injected with 18F-FDG and imaged after 30–38 minutes, for an 8-minute image acquisition consisting of four 2-minute dynamic frames.
Quantitative image analysis for both PIB and FDG was done using our in-house fully automated image processing pipeline [17 (link)]. A global cortical PIB-PET retention ratio was formed by calculating the median uptake over voxels in the prefrontal, orbitofrontal, parietal, temporal, anterior cingulate, and posterior cingulate/precuneus regions of interest (ROIs) for each subject and dividing this by the median uptake over voxels in the cerebellar gray matter ROI of the atlas [18 (link)]. FDG-PET scans were analyzed in a similar manner. We used angular gyrus, posterior cingulate, and inferior temporal cortical ROIs, as described in Landau et al [19 (link)], normalized to pons uptake.
PET images [14 (link)] were acquired using a PET/CT scanner. The 11C PIB-PET scan consisting of four 5-minute dynamic frames was acquired from 40–60 minutes after injection [15 (link), 16 (link)]. 18 Fluorodeoxyglucose (18F-FDG ) PET images were obtained 1 hour after the PIB scan. Subjects were injected with 18F-FDG and imaged after 30–38 minutes, for an 8-minute image acquisition consisting of four 2-minute dynamic frames.
Quantitative image analysis for both PIB and FDG was done using our in-house fully automated image processing pipeline [17 (link)]. A global cortical PIB-PET retention ratio was formed by calculating the median uptake over voxels in the prefrontal, orbitofrontal, parietal, temporal, anterior cingulate, and posterior cingulate/precuneus regions of interest (ROIs) for each subject and dividing this by the median uptake over voxels in the cerebellar gray matter ROI of the atlas [18 (link)]. FDG-PET scans were analyzed in a similar manner. We used angular gyrus, posterior cingulate, and inferior temporal cortical ROIs, as described in Landau et al [19 (link)], normalized to pons uptake.
