182 Chapter 7 uals, and ii) amyloid positive (Aβ+) CN and cognitively impaired (CI) (AD-phenotype) individuals. First, we assessed whether tau PET, atrophy and rCBF showed significant changes over time. Second, we assessed the association between i) baseline and ii) annual change in tau PET (binding potential [BPND]) and longitudinal changes in both cortical thickness and rCBF (R1). Assuming that CBF alterations occur in between tau accumulation and atrophy in the pathophysiological development of AD, we hypothesized that higher tau load at baseline would be strongly associated with a steeper decline in cortical thickness and rCBF in Aβ+ individuals. Furthermore, we hypothesized that larger increases in tau PET over time would be associated with larger decreases in cortical thickness and rCBF in Aβ+ individuals. METHODS Participants We included 61 individuals from the Amsterdam Dementia Cohort (ADC) of the Alzheimer Center Amsterdam [25] of whom 26 were CN Aβ- with subjective cognitive decline (SCD) [26] and 35 Aβ+ with SCD (CN, n=9), or cognitively impaired AD (CI, n=26) [27, 28]. All 61 participants underwent baseline and two year follow-up dynamic [18F]flortaucipir PET and MRI scans, and are referred to as the follow-up sample. In addition, to increase power in our statistical models, we included 86 individuals from the ADC (18 CN and 68 CI) who only underwent baseline dynamic [18F]flortaucipir PET and MRI scans, referred to as the baseline-only sample. Individuals with SCD (nfollow-up + baseline-only=55) were recruited from the SCIENCe cohort [29], which is part of the ADC [25]. All individuals underwent a standardized diagnostic workup, including medical and neurological examination, assessment of vital functions, informant-based history, neuropsychological evaluation, magnetic resonance imaging (MRI) and standard labs. Subsequently, diagnoses were determined by consensus in a multidisciplinary meeting. AD biomarkers in cerebrospinal fluid (CSF) and/or Aβ PET were available for all individuals. Individuals were classified as Aβ+ based on abnormal AD biomarkers (CSF Aβ42 <813 pg/mL [30] and/or abnormal Aβ PET (on visual read)). When both CSF Aβ42 and Aβ PET were available, Aβ PET was used for the determination of Aβ status. All AD patients had abnormal AD biomarkers and are therefore considered in the AD pathophysiological continuum, according to the NIA-AA Research Framework, classified as Aβ+ CI individuals [22]. Individuals with SCD with evidence of Aβ pathology were classified as Aβ+ CN individuals. Amyloid-β status was only determined at baseline. Exclusion criteria included severe traumatic brain injury, abnormalities on MRI likely to interfere with segmentation of tau PET and participation in a drug trial with tau or Aβ-targeting agents. Individuals were
RkJQdWJsaXNoZXIy MjY0ODMw