25 ATN classification in subjective cognitive decline was performed on coronal T1-weighted images averaging scores for the left and right sides (range 0-4) (28). Posterior atrophy (PA) was rated using sagittal, axial and coronal planes of T1 and FLAIR weighted images averaging scores for the left and right sides (range 0-3) (29). Global cortical atrophy (GCA) was rated using axial FLAIR images (range 0-3) (30). The severity of white matter hyperintensities (WMH) was determined on the FLAIR sequence using the Fazekas scale (range 0-3) (31). Lacunes were defined as deep lesions (3-15 mm) with CSF-like signal on all sequences. They were counted and dichotomized into absent (0) of present (≥ 1 lacune). Microbleeds were defined as small dot-like hypointense lesions on T2-weighted images. They were also counted and dichotomized into absent (0) or present (≥ 1 microbleed). An experienced neuroradiologist reviewed all scans. CSF CSF was obtained by lumbar puncture between the L3/L4, L4/L5 or L5/S1 intervertebral space by a 25-gauge needle and syringe and collected in polypropylene tubes (32). Aβ-42, total tau and tau phosphorylated threonine 181 (p-tau) were measured using sandwich ELISA’s (Innotest beta-amyloid1-42 n=579, Innotest hTAU-Ag and Innotest PhosphoTAU-181p) (33). CSF Aβ levels were adjusted for the drift in CSF biomarker analyses that occurred over the years (34). For nine participants, we used Elecsys for analyses of Aβ. These values were transformed to the Innotest-equivalent values by the following formula: Elecsys Aβ (pg/ml) = -365 + 1.87 * Innotest Aβ (pg/ml) (35). PET For n=105 participants, amyloid PET was performed in research context using the tracers [18F]florbetapir (n=19), [18F]florbetaben (n=65), [18F]flutemetamol (n=10) or [11C]- PIB (Pittsburgh compound-B, n=11). The tracers were administered intravenously through a cannula. PET scans were acquired on the following systems: Gemini TF PET-CT, Ingenuity TF PET-CT, and Ingenuity PET/MRI (Philips Healthcare, Best, The Netherlands). During scans, laser beams were used to monitor head movement. For [18F]florbetapir imaging, participants were injected with a tracer dose of approximately 370 megabecquerel (MBq) [18F]florbetapir (20). 90-minutes dynamic PET emission scans were obtained simultaneously starting with tracer injection. For [18F]florbetaben imaging, participants were injected with a tracer dose of approximately 300 MBq [18F] florbetaben (36). The image acquisition window extended from 90 to 110 minutes (4 x 5 minute frames) after dose injection. For [18F]flutemetamol imaging, participants were injected with approximately 191 MBq [18F]flutemetamol (37). The image acquisition window extended from 90 minutes to 110 minutes (4 x 5 minute frames) after dose injection. For [11C]PIB imaging, participants were injected with a tracer dose of approximately 365 MBq [11C]PIB in younger participants and approximately 382 MBq 2
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