Amyloid PET imaging was performed with Pittsburgh Compound B19 (link), synthesized on site with precursor purchased from ABX Biochemical Compounds, Germany. Tau PET was performed with AV1451, synthesized on site with precursor supplied by Avid Radiopharmaceuticals 17 (link). Late uptake amyloid PET images were acquired from 40-60 minutes and tau PET from 80-100 minutes after injection. Methods of amyloid PET data analysis have been described previously. 7 (link),23 Amyloid PET values are expressed both in SUVR units and in centiloid units.24 A tau PET composite reporter region of interest (ROI) was formed from a voxel-number weighted average of the median uptake in the entorhinal, amygdala, parahippocampal, fusiform, inferior temporal, and middle temporal ROIs normalized to the cerebellar crus grey median. 23 PET data was not partial volume corrected.
MRI was performed on one of three 3 Tesla systems from the same vendor (General Electric, Waukesha WI, USA). The primary MRI measure was a FreeSurfer (v5·3) derived temporal lobe cortical thickness composite reporter ROI of the entorhinal, inferior temporal, middle temporal, and fusiform ROIs. 23 These were consistently among the top performing ROIs across our previous ROI selection studies discriminating between A– clinically normal and A+ impaired individuals. 25 (link), 26 (link) As an alternative measure of neurodegeneration we used the sum of right and left hippocampal volumes from FreeSurfer adjusted for total intracranial volume (HVa) as described in 27 (link). The MRI acquisition also included a FLAIR sequence from which white matter hyperintensity volume was measured using an algorithm developed in-house.28 (link)We have recently conducted a thorough examination of several different methods for selecting cut-points to define abnormality on amyloid PET, tau PET and MRI thickness. 23 The optimal amyloid PET cut-point of SUVR 1·42 (centiloid 19) was based on the threshold value beyond which the rate of change in amyloid PET reliably increases. We determined cut-points for tau PET and MRI thickness by maximizing the accuracy (i.e., maximizing sensitivity plus specificity) in discriminating between amyloid positive individuals with mild cognitive impairment or dementia versus MCSA CN individuals aged 30-49. Based on this method, the cutpoint for tau PET was 1·23 SUVR and for MRI cortical thickness was 2·67 mm. Each participant in the present study was classified into one of the eight ATN states using these cut-points. As a secondary analysis, abnormal N was defined as HVa less than -1·15 cm3 (link). This HVa cut-point was derived in the same manner and using the same samples described in. 23
MRI was performed on one of three 3 Tesla systems from the same vendor (General Electric, Waukesha WI, USA). The primary MRI measure was a FreeSurfer (v5·3) derived temporal lobe cortical thickness composite reporter ROI of the entorhinal, inferior temporal, middle temporal, and fusiform ROIs. 23 These were consistently among the top performing ROIs across our previous ROI selection studies discriminating between A– clinically normal and A+ impaired individuals. 25 (link), 26 (link) As an alternative measure of neurodegeneration we used the sum of right and left hippocampal volumes from FreeSurfer adjusted for total intracranial volume (HVa) as described in 27 (link). The MRI acquisition also included a FLAIR sequence from which white matter hyperintensity volume was measured using an algorithm developed in-house.28 (link)We have recently conducted a thorough examination of several different methods for selecting cut-points to define abnormality on amyloid PET, tau PET and MRI thickness. 23 The optimal amyloid PET cut-point of SUVR 1·42 (centiloid 19) was based on the threshold value beyond which the rate of change in amyloid PET reliably increases. We determined cut-points for tau PET and MRI thickness by maximizing the accuracy (i.e., maximizing sensitivity plus specificity) in discriminating between amyloid positive individuals with mild cognitive impairment or dementia versus MCSA CN individuals aged 30-49. Based on this method, the cutpoint for tau PET was 1·23 SUVR and for MRI cortical thickness was 2·67 mm. Each participant in the present study was classified into one of the eight ATN states using these cut-points. As a secondary analysis, abnormal N was defined as HVa less than -1·15 cm3 (link). This HVa cut-point was derived in the same manner and using the same samples described in. 23
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