112 Chapter 5 METHODS Participants We included 79 subjects from the Amsterdam Dementia Cohort with either probable AD dementia[27] (n=68) or mild cognitive impairment (MCI) due-to-AD[28] (n = 11), with positive amyloid-β biomarkers[29-31]. All subjects underwent a standardized dementia screening, including medical history, extensive neuropsychological assessment, physical and neurological examination, lumbar puncture, blood tests, electroencephalography, and brain MRI. Diagnosis was established by consensus in a multidisciplinary meeting. The diagnosis of MCI/AD met core clinical criteria[27, 28] according to the National Institute on Aging and Alzheimer’s Association (NIA-AA) and were biomarker supported, with an AD-like CSF profile (i.e., tau/Aβ42 fraction >0.52)[32, 33] and/or an Aβ-PET scan ([11C]PiB or [18F]florbetaben) showing substantial amyloid accumulation when visually assessed by an experienced nuclear medicine physician (BvB). When both CSF and PET measures of amyloid were available, PET visual read was used to determine amyloid status. Subjects were assigned to either the early- or late-onset AD group, based on a median split (ageat-PET). Since the median age in our sample was 66 years, this led to a similar age cut-off compared to the conventional threshold of 65 years[2, 3, 6, 34]. The sample included eight patients meeting criteria for an atypical variant of AD, including two behavioral variant AD (bvAD) and six posterior cortical atrophy (PCA) patients[31, 35]. All atypical AD patients were part of the early-onset AD group, except one bvAD patient. Exclusion criteria for all participants were (1) dementia not due-to-AD, (2) significant cerebrovascular disease on MRI (e.g. major cerebrovascular accident), (3) major traumatic brain injury, (4) major psychiatric or neurological disorders other than AD, (5) (recent) substance abuse. The study protocol was approved by the Medical Ethics Review Committee of the Amsterdam UMC, location VU Medical center. All patients provided written informed consent. [18F]flortaucipir PET Acquisition and processing of [18F]flortaucipir PET images is described in detail elsewhere[17, 25, 36]. In short, dynamic 130min [18F]flortaucipir PET scans were acquired on a Philips Ingenuity TF-64 PET/CT scanner. The scanning protocol consisted of two dynamic PET scans of 60 and 50min, respectively, with an in-between 20min break[36]. The first 60min dynamic scan started simultaneously with a bolus injection of approximately 234±14 MBq [18F]flortaucipir (injected mass 1.2±0.9 μg). The second PET scan was co-registered to the first dynamic PET scan using Vinci software (Max Planck Institute, Germany). PET data were acquired in list mode and subsequently reconstructed using 3D-RAMLA including standard corrections
RkJQdWJsaXNoZXIy MjY0ODMw