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Abstract
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 [CU+], 31 with prodromal AD [mild cognitive impairment; MCI+], and 24 with AD dementia [DEM+]) 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 CU+ groups during the 2-y period, global cortical SUVR increased by 0.06 (2.9%) in the MCI+ group and 0.19 (8.0%) in the DEM+ group at follow-up. The MCI+ group was associated with additional tau accumulation predominantly in the medial and inferior temporal cortices, whereas the DEM+ group showed increases in the lateral temporal cortex. Progressive tau accumulation occurred in the diffuse cortical areas in the MCI+ patients who developed dementia and the DEM+ 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.

Author information

Cho H1, Choi JY2,3, Lee HS4, Lee JH2, Ryu YH5, Lee MS1, Jack CR Jr6, Lyoo CH7.
1
Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
2
Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
3
Division of RI-Convergence Research, Korea Institute Radiological and Medical Sciences, Seoul, South Korea.
4
Biostatistics Collaboration Unit, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea; and.
5
Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea lyoochel@yuhs.ac ryuyh@yuhs.ac.
6
Department of Radiology, Mayo Clinic, Rochester, Minnesota.
7
Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea lyoochel@yuhs.ac ryuyh@yuhs.ac.