113 Tau PET and cognition in early- and late onset AD for dead time, decay, attenuation, random, and scatter. Patients also underwent 3DT1-weighted MRI (Ingenuity TF PET/MR, Philips Medical Systems, The Netherlands) for anatomical and tissue segmentation purposes. Image analysis The 3DT1-weighted MRI images were co-registered to their corresponding PET images using Vinci software. Anatomical regions-of-interest according to the Hammers template were subsequently delineated on the MR images and superimposed on the PET scan using PVElab[37]. Using receptor parametric mapping (RPM) with cerebellar gray matter as reference region we generated binding potential (BPND) maps as a measure for tau pathology. Additionally, and similar to previous work[17, 25], R1 was generated as a proxy for rCBF[18]. Partial volume correction was applied to the PET images using Van Cittert iterative deconvolution methods (IDM), combined with highly constrained back-projections (HYPR) as described previously [17, 38, 39]. Uncorrected data are shown in the main manuscript and partial volume-corrected data are shown in the Supplemetary material. In line with a previous study[17], we calculated BPND and R1 in frontal, occipital, parietal, medial and lateral temporal bilateral cortical lobar regions-of-interest. In addition to the region-of-interest analyses, we performed voxel-wise analyses to 1) create average images of the different diagnostic groups (early- and late-onset AD without atypical AD cases, PCA and bvAD), and 2) explore more fine-grained differences in [18F]flortaucipir BP ND and R1 between early- and late-onset AD. Therefore, we warped all native space parametric BPND and R1 images to Montreal Neurological Institute (MNI152) space using the transformation matrixes derived from warping the co-registered T1-weighted MRI scans to MNI space using Statistical Parametric Mapping (SPM) version 12. All warped images were visually inspected for transformation errors and quality control. Average images were calculated using SPM12. Neuropsychological assessment We included eight neuropsychological tests (<1 year of PET scan), including the Dutch version of the Rey Auditory Verbal Learning Test immediate recall and delayed recall (episodic memory), Digit Span forward and backward (attention/executive functioning), Trail Making Test [TMT] version A and B (attention/executive functioning), Letter Fluency test (D-A-T) (executive functioning) and Category Fluency version animals (language)[40]. TMT-A and -B scores were inverted so that lower scores indicated worse performance. In addition, the Mini-Mental State Examination (MMSE) served as a measure of global cognition[41]. For participants who had TMT-A available but were missing TMT-B, we estimated the TMT-B by multiplying the time needed to 5
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