Progressive tau accumulation in Alzheimer's disease: two-year follow-up study.

Background: Tau positron emission tomography (PET) enabled in vivo visualization and quantitation of tau pathology in Alzheimer disease (AD). In cross-sectional tau PET studies, tau burden reflected disease severity and phenotypic variation. We investigated longitudinal change in cortical tau accumulation and its associations with cognitive decline in patients with Alzheimer disease (AD). Methods: We enrolled 107 participants [45 amyloid β (Aβ)-negative cognitively unimpaired (CU-), 7 Aβ-positive cognitively unimpaired (CU+), 31 prodromal AD (mild cognitive impairment; MCI+), and 24 AD dementia (DEM+)] who completed two baseline PET scans (18 F-flortaucipir and 18 F-florbetaben), magnetic resonance imaging, and neuropsychological tests. All participants underwent the same assessments after two years. After correcting for partial volume effect, standardized uptake value ratio (SUVR) images were created. By using a linear mixed effect model, the changes in SUVR values across time points were investigated 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 values in CU- and CU+ groups during the two-year period, global cortical SUVR values increased by 0.06 (2.9%) in MCI+ and 0.19 (8.0%) in DEM+ at follow-up. MCI+ was associated with additional tau accumulation predominantly in the medial and inferior temporal cortices, while the DEM+ showed increases in the lateral temporal cortex. Progressive tau accumulation occurred in the diffuse cortical areas in the MCI+ patients who developed dementia and DEM+ patients who showed deterioration of global cognition, while 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 the progression of tau accumulation in the diffuse association neocortex. Conclusion: Progressive tau accumulation occurs in prodromal AD and AD dementia patients in the cortical areas at different levels of tau stages. Progression of cognitive dysfunction may be related to the additional tau accumulation in regions for higher Braak's stages. 18 F-flortaucipir PET is an imaging biomarker for monitoring the progression of AD.