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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 ((18)F-flortaucipir and (18)F-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. (18)F-flortaucipir PET is an imaging biomarker for monitoring the progression of AD.

Off-target binding in the basal ganglia is commonly observed in the 18F-AV-1451 PET studies of the elderly. We sought to investigate the relationship between this phenomenon in the basal ganglia and iron accumulation using iron-sensitive R2* MRI. Methods: Fifty-nine healthy controls and 61 patients with Alzheimer disease and mild cognitive impairment underwent 18F-AV-1451 PET and R2* MRI studies. A correlation analysis was performed for age, 18F-AV-1451 binding, and R2* values. Results: There was an age-related increase in both 18F-AV-1451 binding in the basal ganglia and R2* values in the putamen in both the controls and the Alzheimer disease/mild cognitive impairment patients. 18F-AV-1451 binding in the basal ganglia increased with R2* values. Conclusion: Off-target 18F-AV-1451 binding in the basal ganglia is associated with the age-related increases in iron accumulation. Postmortem studies are required to further investigate the nature of this association.