134 Chapter 6 METHODS Population We included 187 cognitively normal individuals from the SCIENCe cohort, which is part of the Amsterdam Dementia Cohort (27, 28). All participants with available [18F] florbetapir PET and MRI and available cognitive data were included. PET scans used in this study were acquired between 2015 and 2021. One hundred and seventyfive individuals were referred to the memory clinic by their general physician, a geriatrician, or a neurologist. All underwent an extensive standardized diagnostic work-up, including a neurological and neuropsychological examination, laboratory testing and brain MRI, which was read by an experienced neuroradiologist. In a consensus meeting, individuals were categorized as having subjective cognitive decline when clinical and cognitive investigations were normal and criteria were not met for mild cognitive impairment (MCI) or dementia, nor for other neurological or psychiatric diseases that could be the cause of cognitive complaints. Participants were followed up annually, during which neuropsychological testing and clinical investigation were repeated. In addition, 12 participants were included via the Dutch Brain Research Registry (hersenonderzoek.nl). All experienced cognitive complaints in absence of objective impairment and all received the same baseline work-up. Image acquisition PET scans were acquired on an Ingenuity TF PET-CT (n=140) or a Gemini TF PET-CT (n=47; Philips, Best, the Netherlands) scanner which were calibrated to each other. Dynamic PET scans of 90 minutes (n=140) were obtained starting simultaneously with tracer injection of approximately 370 MBq [18F]florbetapir. During the course of the study, we demonstrated that scan duration could be reduced without compromising the reliability of results (24). Therefore, subsequent scans had a duration of 70 minutes (n=43). The scan was terminated early in four instances due to participant related issues (three after 60 minutes, one after 79 minutes). These scans were nonetheless included because quantification was reliable in these subjects with relatively low amyloid load (24). Follow-up scans were available for n=83 (44%) (n=17 90-minute scan; n=66 70-minute scan). Mean time between the two PET scans was 2.6 ± 0.7 years. In addition, all individuals underwent structural MRI. The protocol included 3D T1weighted images, 3D T2-weighted images, and 3D T2-weighted fluid-attenuated inversion-recovery (FLAIR) images (29).