228 Chapter 9 SUMMARY & DISCUSSION The general aim of this thesis was to gain a better understanding of both methodological as well as biological/clinical aspects of dynamic [18F]flortaucipir PET, which yields information about tau pathology as well as rCBF, in the context of AD. By gaining a better understanding of the use of tau PET we can optimize and direct its use in clinical and research settings. In the first part of this thesis we assessed whether methodological optimization of [18F]flortaucipir PET acquisition would be possible, by i) investigating whether we could reduce the dynamic scanning time of [18F]flortaucipir PET scans without compromising on quantitative accuracy, and ii) investigating whether dynamic acquisition is required for obtaining quantitatively reliable measures of tau pathology in a longitudinal setting. We demonstrated that dynamic scanning protocols can be shorted without compromising on quantitative accuracy, and that static imaging protocols are sufficient in settings (including longitudinal follow-up) where changes in flow are expected to be small. In the second part of this thesis we aimed to gain better understanding of the relationship between tau PET with clinical measures, specifically i) (longitudinal) cognition, and ii) neuronal injury (rCBF and atrophy). Furthermore, we investigated the temporal dynamics of biomarker changes in the AT(N) classification system. We demonstrated that tau PET is predictive of both cognitive decline and atrophy, and that there is considerable variability across individuals in the order of ATN biomarkers becoming abnormal. In this chapter we summarize the main findings and discuss these in the context of the existing literature, followed by future implications and final conclusions.
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