Precuneus

Amyloid PET imaging was performed with Pittsburgh Compound B (Klunk et al., 2004 (link)) and FDG PET was obtained on the same day. CT was obtained for attenuation correction. Amyloid PET images were acquired from 40–60 min and FDG from 30–40 min after injection. Amyloid PET and FDG PET were analysed with our in-house fully automated image processing pipeline (Senjem et al., 2005 (link)) where image voxel values are extracted from automatically labelled regions of interest propagated from an MRI template. An amyloid PET standardized uptake value ratio (SUVR) was formed from the prefrontal, orbitofrontal, parietal, temporal, anterior cingulate, and posterior cingulate/precuneus regions of interest normalized to the cerebellum (grey plus white matter). The data were partial volume corrected for voxel CSF content using segmented co-registered MRI. An Alzheimer’s disease-characteristic FDG PET SUVR was formed from the angular gyrus, posterior cingulate, and inferior temporal cortical regions of interest normalized to pons and vermis (Landau et al., 2011 (link)). FDG PET data were not partial volume corrected. We and others have reported previously that diagnostic performance is slightly better if amyloid PET is partial volume corrected (Lowe et al., 2009 (link); Su et al., 2015 (link)), and is much better if FDG PET is not partial volume corrected (Lowe et al., 2009 (link); Curiati et al., 2011 (link)). Consequently these are the methods we used in the present analysis.
MRI was performed on one of three 3 T systems from the same vendor. Two MRI measures were used. We summed right and left hippocampal volumes from Freesurfer (v 5.3), and adjusted them for total intracranial volume (TIV) by calculating the residual from a linear regression of hippocampal volume (y) versus intracranial volume (x) among 133 cognitively normal subjects aged 30 to 59 (described in Jack et al., 2014a (link)). Adjusted hippocampal volume can be interpreted as the deviation in cm³ in a subject’s hippocampal volume from what is expected given their TIV. The second MRI measure was an Alzheimer’s disease signature cortical thickness measure composed of the following individual cortical thickness regions of interest: entorhinal, inferior temporal, middle temporal, and fusiform. In-house evaluation indicated that the Alzheimer’s disease signature composite cortical thickness measure was not correlated with TIV (Spearman rank correlation r_s = −0.09, P = 0.16) in cognitively non-impaired individuals aged 50–60 (a subgroup chosen in which we are reasonably certain subjects do not harbour latent age-related pathology), whereas hippocampal volume and TIV were strongly correlated (r_s = 0.62, P < 0.001). We therefore used TIV-adjusted hippocampal volume, but did not adjust the Alzheimer’s disease signature cortical thickness measure for TIV an approach adopted by other groups (Dickerson et al., 2009 (link)).

Amyloid PET scans with ¹¹C‐Pittsburgh Compound B (or PiB) were obtained via previously described methods, and images were processed using the PET unified pipeline (PUP, https://github.com/ysu001/PUP).³⁴, ³⁵ Briefly, dynamically acquired PET data were reconstructed into frames that underwent affine registration to correct for inter‐frame motion.³⁶, ³⁷ Standardized uptake value ratios (SUVRs) from the 30–60 min post‐injection window were calculated using the cerebellar gray matter as the reference region.³⁴, ³⁸ Images were smoothed using a gaussian kernel to achieve a spatial resolution of 8 mm. Data were then summarized in regions of interest defined by the Desikan–Killiany atlas derived from the MRI. Partial volume correction was implemented via a geometric transfer matrix approach.³⁵, ³⁹ An amyloid PET summary value was calculated from the arithmetic mean of SUVRs for the following bilateral regions (average of right‐ and left‐sided structures): precuneus, superior frontal and rostral middle frontal regions, lateral orbitofrontal and medial orbitofrontal regions, and superior temporal and middle temporal regions.³⁴ Individuals were classified as amyloid positive if the mean cortical SUVR was greater than 1.42.³⁴ Centiloid values were calculated using Equation 1.⁴⁰ $$\mathrm{Centiloid}=45.0\ast \mathrm{mean}\mathrm{cortical}\mathrm{SUVR}-47.5$$