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.

中文翻译：

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阿尔茨海默氏病中渐进性Tau积累：2年随访研究。

Tau PET可以在体内可视化和定量阿尔茨海默病（AD）中tau的积累。在横断面tau PET研究中，tau负担反映了疾病的严重程度和表型变异。我们调查了皮质tau积累的纵向变化及其与AD患者认知能力下降的关系。方法：我们招募了107名参与者（45名淀粉样蛋白-β阴性认知功能障碍[CU-]，7名淀粉样蛋白-β阳性认知功能障碍[CU +]，31名先驱性AD（轻度认知障碍； MCI +）和24名AD痴呆[ DEM +]），他们完成了2次基线PET扫描（18F-flortaucipir和18F-florbetaben），MRI和神经心理学测试。所有参与者在2年后都接受了相同的评估。校正部分体积效果后，我们创建了SUV比率（SUVR）图像。通过使用线性混合效应模型，我们调查了每个组中SUVR随时间的变化。我们还研究了tau积累的进展与认知能力下降之间的相关性。结果：与在2年期间CU-和CU +组的整体皮质SUVR没有变化相比，MCI +组的整体皮质SUVR增加了0.06（2.9％），而DEM +组的整体皮质SUVR增加了0.19（8.0％）。跟进。MCI +组主要在内侧和下颞叶皮质中与额外的tau积累相关，而DEM +组则在外侧颞叶皮质中增加。在患有痴呆症的MCI +患者和表现出整体认知能力下降的DEM +患者中，渐进的tau积累发生在弥漫性皮质区域。而在那些没有表现出认知能力恶化的人中，颞外侧皮层的额外tau积聚仅增加了一点点。整体认知和语言功能的恶化与新皮层中弥漫性tau积累的进展有关。结论：前驱性AD和DEM患者在不同tau积累水平的皮质区发生渐进性tau积累。认知功能障碍的进展可能与较高Braak阶段的区域中额外的tau积累有关。18F-flortaucipir PET是用于监视AD进展的成像生物标志物。结论：前驱性AD和DEM患者在不同tau积累水平的皮质区发生tau积累。认知功能障碍的进展可能与较高Braak阶段的区域中额外的tau积累有关。18F-flortaucipir PET是用于监视AD进展的成像生物标志物。结论：前驱性AD和DEM患者在不同tau积累水平的皮质区发生渐进性tau积累。认知功能障碍的进展可能与较高Braak阶段的区域中额外的tau积累有关。18F-flortaucipir PET是用于监视AD进展的成像生物标志物。