144 Chapter 6 METHODS Participants We included 129 participants who underwent dynamic 18F-flortaucipir PET between 2015 and 2021 for research purposes at the Amsterdam UMC (Amsterdam, The Netherlands). The study population consisted of participants from the Amsterdam Dementia Cohort (ADC) [22] and the Subjective Cognitive Impairment Cohort (SCIENCe) [23] with diagnoses of either subjective cognitive decline (SCD) [24], mild cognitive impairment (MCI) due to AD or AD dementia [25, 26]. In addition, healthy controls underwent 18F-flortaucipir PET as control participants. Participants were classified as cognitively impaired (CI; MCI and AD dementia) or cognitively unimpaired (CU; SCD and healthy controls). Exclusion criteria included a history of moderate or severe traumatic brain injury and (prior) use of amyloid-β or tau targeting drugs [27]. Furthermore, participants had to have at least two neuropsychological assessments available, of which at least one took place within a year from the baseline PET scan and at least one after the PET scan. All participants visited the memory clinic and underwent a standardized dementia screening, including clinical evaluation, extensive behavioral and neuropsychological assessment, lumbar puncture, and brain magnetic resonance imaging (MRI). Diagnosis was established by consensus in a multidisciplinary meeting. The diagnosis of MCI due to AD and AD dementia met core clinical criteria complying with the National Institute on Aging and Alzheimer’s Association (NIA-AA), and were biomarker supported by means of positive amyloid-β PET and/or CSF biomarkers [27, 28]. All studies were approved by the Medical Ethics Review Committee of the VU University Medical Center (Amsterdam, the Netherlands). All participants provided written informed consent prior to study participation. Tau PET and MRI acquisition and analyses All participants underwent baseline 18F-flortaucipir PET, a subset (n=90, 70%) underwent follow-up 18F-flortaucipir PET after 2.1±0.5 years. All scans were acquired using a dual time-point dynamic protocol, starting immediately after 18F-flortaucipir administration and acquisitions included at least the 0-30 minutes and 80-100 minutes post-injection time windows as previously described [27, 29, 30]. All scans were acquired on a Philips TF-64 PET/CT scanner. Low dose CT scans were acquired immediately prior to both parts of the dynamic scan for attenuation correction purposes. Participants additionally underwent three-dimensional T1-weighted MRI on a 3 Tesla scanner for brain region-of-interest analyses. PET image analysis has been described previously [31-33]. Briefly, individual T1-weighted MRI scans were co-registered to native PET space, using Vinci software (Max Plank Institute, Cologne,
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