Brain MRI are performed using a 3.0-Tesla scanner (GE Medical Systems, Milwaukee, WI), including fluid attenuated inversion recovery (FLAIR), susceptibility weighted image, and 3-dimensional (3D) T1-weighted images. The white matter hyperintensities (WMHs) are rated using a visual rating scale of axial FLAIR images. In brief, periventricular WMHs and deep WMHs are evaluated separately and rated as minimal (grade 1), moderate (grade 2), or severe (grade 3).[10 (link)] Lacunes are defined as small lesions (3–15 mm in diameter), hyperintense on T2-, and hypointense on T1-weighted images, with a perilesional halo on FLAIR.[11 (link)] Cerebral cortical microbleeds are defined as round and homogeneously low-signal lesions <10 mm in diameter on susceptibility weighted image.[11 (link)] Hippocampal atrophy is rated on coronal T1-weighted images using Scheltens visual rating scale.[12 (link)] The number of lacunes, number of microbleeds, degree of WMH, and degree of hippocampal atrophy will be measured by a trained neurologist blinded to the data.
Florbetaben (18F) PET scans are acquired following the standardized protocol.[13 (link)] Using PET scans, a whole brain visual interpretation is performed by a trained doctor in nuclear medicine who is blinded t the patient diagnosis. In addition, quantitative neuroimaging analyses are performed using PET scans and MRI 3D-T1 images. First, amyloid depositions were assessed using MATLAB version 2013a and SPM8 (http://www.fil.ion.ucl.ac.uk/spm/software/spm8). Individual 3D T1-weighted MRI scans are estimated and co-registered into corresponding PET images. A volume-based template, incorporating 90 regions-of-interest, is aligned to individual T1-weighted MRI scans. The voxels of florbetaben PET images were scaled using the mean uptake value in the cerebellar gray matter to calculate the standardized uptake value ratio (SUVR), and partial volume corrections are performed. The mean SUVR values are calculated as a global SUVR. Second, the MRI volumetric analysis are performed using AQUA 2.0 program (Neurophet, South Korea). The details of the MRI segmentation and data analysis were described elsewhere.[14 (link)] A normative dataset is obtained using the East-Asian dataset described in a previous study,[15 (link)] and the adjusted volume (z score) corrected with total intracranial volume, age, and sex is measured.
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