229 Summary & Discussion The key findings of this thesis include: Part 1: Methodological applications i. Dynamic [18F]flortaucipir PET scans can be shortened from 110 to only 50 minutes without loss of accuracy. ii. Longitudinal semi-quantitative (SUVr) and quantitative (BPND) parameters are comparable for [18F]flortaucipir. Part 2a: Clinical applications - cognition i. Tau pathology and low rCBF are both independently associated with worse cognitive performance (cross-sectionally), indicating that each biomarker independently contributes to cognitive impairment in AD. ii. Compared to LOAD, the degree of tau pathology and rCBF is more strongly associated with cognitive impairment in EOAD. iii. Both baseline and change in tau load are predictive for longitudinal cognitive trajectories across domains (when corrected for rCBF), underlining that tau PET is a valuable tool in predicting cognition. Part 2b: Clinical applications – neuronal injury i. Higher tau load is related to accelerated cortical thinning, but not to decreases in rCBF, and tau PET load at baseline better predicts cortical thinning than change of tau PET signal. Part 2c: Clinical applications – AT(N) classification system i. There is considerable variability across individuals in the order of ATN biomarkers becoming abnormal. 9
RkJQdWJsaXNoZXIy MjY0ODMw