Tau PET enables in vivo visualization and quantitation of tau accumulation in Alzheimer disease (AD). In cross-sectional tau PET studies, tau burden reflects disease severity and phenotypic variation. We investigated longitudinal changes in cortical tau accumulation and their association with cognitive decline in patients with AD. Methods: We enrolled 107 participants (45 amyloid-β–negative cognitively unimpaired [CU−], 7 amyloid-β–positive cognitively unimpaired [CU1], 31 with prodromal AD [mild cognitive impairment; MCI1], and 24 with AD dementia [DEM1]) who completed 2 baseline PET scans (18F-flortaucipir and 18F-florbetaben), MRI, and neuropsychologic tests. All participants underwent the same assessments after 2 y. After correcting for partial-volume effect, we created SUV ratio (SUVR) images. By using a linear mixed-effect model, we investigated the changes in SUVR across time within each group. We also investigated a correlation between the progression of tau accumulation and cognitive decline. Results: In contrast to no change in global cortical SUVR in the CU− and CU1 groups during the 2-y period, global cortical SUVR increased by 0.06 (2.9%) in the MCI1 group and 0.19 (8.0%) in the DEM1 group at follow-up. The MCI1 group was associated with additional tau accumulation predominantly in the medial and inferior temporal cortices, whereas the DEM1 group showed increases in the lateral temporal cortex. Progressive tau accumulation occurred in the diffuse cortical areas in the MCI1 patients who developed dementia and the DEM1 patients who showed deterioration of global cognition, whereas there was only a small increase of additional tau accumulation in the lateral temporal cortex in those who did not show worsening of cognition. Deterioration of global cognition and language functions was associated with progression of diffuse tau accumulation in the association neocortex. Conclusion: Progressive tau accumulation occurs in prodromal AD and DEM patients in the cortical areas at different levels of tau accumulation. Progression of cognitive dysfunction may be related to the additional tau accumulation in regions of higher Braak stage. 18F-flortaucipir PET is an imaging biomarker for monitoring the progression of AD.
Bibliographical noteFunding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (NRF-2017R1A2B2006694), which is funded by the Ministry of Education (NRF-2018R1D1A1B07049386). This research was also supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), which is funded by the Ministry of Health and Welfare, Republic of Korea (grant HI18C1159). Support was also received through a faculty research grant from Yonsei University College of Medicine (6-2018-0068). Clifford Jack, Jr., consults for Lily and serves on an independent data monitoring board for Roche but receives no personal compensation from any commercial entity. He receives research support from the NIH and the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic. No other potential conflict of interest relevant to this article was reported.
All Science Journal Classification (ASJC) codes
- Radiology Nuclear Medicine and imaging