143 Longitudinal tau PET and cognition INTRODUCTION Tau pathology is a main pathological hallmark of Alzheimer’s disease (AD) and is closely associated with cognitive decline [1]. Imaging studies have shown that both the burden and the topography of tau PET binding correlates with performance in specific cognitive domains according to established brain–behavior relationships [2-4]. Furthermore, they support the sequential order of events in the disease in which tau pathology occurs prior to neurodegenerative and cognitive changes [5]. In addition, longitudinal studies demonstrate that tau PET binding at baseline is associated with cognitive changes over time and there is emerging evidence that longitudinal changes in tau PET binding are associated with cognitive changes and progression to more severe clinical stages across the AD spectrum [2, 4, 6-9]. A major advantage of acquiring tau PET using a dynamic scanning protocol is that besides a more accurate reflection of the actual tau load (i.e. binding potential [BPND]), one can obtain information about R1, a measure of relative cerebral blood flow (rCBF) that is tightly linked to metabolic activity (18F-FDG PET) and 15O-H 2O PET (i.e., the ‘gold standard’ for measuring flow) [10-12]. Growing evidence suggests a role for CBF (measured with SPECT or MRI) as a measure of neuronal injury in the context of cognitive decline. Studies demonstrate mixed results when it comes to the associations between CBF and cognitive decline in the context of AD [13-16]. Lower CBF at baseline has been found in patients with cognitive decline compared to healthy controls of the same age. Longitudinal studies, on the contrary, did not consistently support a link between CBF reductions and cognitive decline, but those studies may have been underpowered to detect small effects due to limited sample sizes [17-19]. A recent meta-regression analysis revealed a positive correlation between the decrease in global CBF and cognitive decline over time in AD [20, 21]. The majority of studies investigating cognition in the context of tau pathology or CBF only assess a single cognitive domain or a single test for global cognitive functioning (such as MMSE). In this study we aimed to assess the association between i) baseline tau pathology and rCBF, and ii) change in tau pathology and rCBF, with cognitive decline (over time) on tests of memory, executive functioning and global level in individuals along the AD spectrum. We hypothesized that increases in tau PET BPND would be associated with steeper rate of cognitive decline particularly in cognitively impaired (CI) individuals. Particularly, we expect tau PET BPND in early-stage disease regions (such as Braak I) to be mainly associated with memory, and tau PET BPND in more late-stage disease regions (Braak III-VI) to be mainly associated with executive and global cognitive functioning. For rCBF, we hypothesized that global decreases would be associated with decreased global cognitive functioning. 6
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