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Accuracy of Tau Positron Emission Tomography as a Prognostic Marker in Preclinical and Prodromal Alzheimer Disease: A Head-to-Head Comparison Against Amyloid Positron Emission Tomography and Magnetic Resonance Imaging.
JAMA Neurology ( IF 29.0 ) Pub Date : 2021-08-01 , DOI: 10.1001/jamaneurol.2021.1858
Rik Ossenkoppele 1, 2 , Ruben Smith 1 , Niklas Mattsson-Carlgren 1, 3, 4 , Colin Groot 2 , Antoine Leuzy 1 , Olof Strandberg 1 , Sebastian Palmqvist 1 , Tomas Olsson 5 , Jonas Jögi 6 , Erik Stormrud 1, 7 , Hanna Cho 8 , Young Hoon Ryu 9 , Jae Yong Choi 9, 10 , Adam L Boxer 11 , Maria L Gorno-Tempini 11 , Bruce L Miller 11 , David Soleimani-Meigooni 11 , Leonardo Iaccarino 11 , Renaud La Joie 11 , Suzanne Baker 12 , Edilio Borroni 13 , Gregory Klein 13 , Michael J Pontecorvo 14 , Michael D Devous 14 , William J Jagust 12, 15 , Chul Hyoung Lyoo 8 , Gil D Rabinovici 11, 16, 17, 18 , Oskar Hansson 1, 7
Affiliation  

Importance Tau positron emission tomography (PET) tracers have proven useful for the differential diagnosis of dementia, but their utility for predicting cognitive change is unclear. Objective To examine the prognostic accuracy of baseline fluorine 18 (18F)-flortaucipir and [18F]RO948 (tau) PET in individuals across the Alzheimer disease (AD) clinical spectrum and to perform a head-to-head comparison against established magnetic resonance imaging (MRI) and amyloid PET markers. Design, Setting, and Participants This prognostic study collected data from 8 cohorts in South Korea, Sweden, and the US from June 1, 2014, to February 28, 2021, with a mean (SD) follow-up of 1.9 (0.8) years. A total of 1431 participants were recruited from memory clinics, clinical trials, or cohort studies; 673 were cognitively unimpaired (CU group; 253 [37.6%] positive for amyloid-β [Aβ]), 443 had mild cognitive impairment (MCI group; 271 [61.2%] positive for Aβ), and 315 had a clinical diagnosis of AD dementia (315 [100%] positive for Aβ). Exposures [18F]Flortaucipir PET in the discovery cohort (n = 1135) or [18F]RO948 PET in the replication cohort (n = 296), T1-weighted MRI (n = 1431), and amyloid PET (n = 1329) at baseline and repeated Mini-Mental State Examination (MMSE) evaluation. Main Outcomes and Measures Baseline [18F]flortaucipir/[18F]RO948 PET retention within a temporal region of interest, MRI-based AD-signature cortical thickness, and amyloid PET Centiloids were used to predict changes in MMSE using linear mixed-effects models adjusted for age, sex, education, and cohort. Mediation/interaction analyses tested whether associations between baseline tau PET and cognitive change were mediated by baseline MRI measures and whether age, sex, and APOE genotype modified these associations. Results Among 1431 participants, the mean (SD) age was 71.2 (8.8) years; 751 (52.5%) were male. Findings for [18F]flortaucipir PET predicted longitudinal changes in MMSE, and effect sizes were stronger than for AD-signature cortical thickness and amyloid PET across all participants (R2, 0.35 [tau PET] vs 0.24 [MRI] vs 0.17 [amyloid PET]; P < .001, bootstrapped for difference) in the Aβ-positive MCI group (R2, 0.25 [tau PET] vs 0.15 [MRI] vs 0.07 [amyloid PET]; P < .001, bootstrapped for difference) and in the Aβ-positive CU group (R2, 0.16 [tau PET] vs 0.08 [MRI] vs 0.08 [amyloid PET]; P < .001, bootstrapped for difference). These findings were replicated in the [18F]RO948 PET cohort. MRI mediated the association between [18F]flortaucipir PET and MMSE in the groups with AD dementia (33.4% [95% CI, 15.5%-60.0%] of the total effect) and Aβ-positive MCI (13.6% [95% CI, 0.0%-28.0%] of the total effect), but not the Aβ-positive CU group (3.7% [95% CI, -17.5% to 39.0%]; P = .71). Age (t = -2.28; P = .02), but not sex (t = 0.92; P = .36) or APOE genotype (t = 1.06; P = .29) modified the association between baseline [18F]flortaucipir PET and cognitive change, such that older individuals showed faster cognitive decline at similar tau PET levels. Conclusions and Relevance The findings of this prognostic study suggest that tau PET is a promising tool for predicting cognitive change that is superior to amyloid PET and MRI and may support the prognostic process in preclinical and prodromal stages of AD.

中文翻译:

Tau 正电子发射断层扫描作为临床前和前驱阿尔茨海默病预后标志物的准确性:与淀粉样蛋白正电子发射断层扫描和磁共振成像的头对头比较。

重要性 Tau 正电子发射断层扫描 (PET) 示踪剂已被证明可用于痴呆的鉴别诊断,但它们在预测认知变化方面的效用尚不清楚。目的检查基线氟 18 (18F)-flortaucipir 和 [18F]RO948 (tau) PET 在阿尔茨海默病 (AD) 临床谱中个体的预后准确性,并与已建立的磁共振成像进行头对头比较(MRI) 和淀粉样蛋白 PET 标记。设计、设置和参与者这项预后研究收集了 2014 年 6 月 1 日至 2021 年 2 月 28 日韩国、瑞典和美国的 8 个队列的数据,平均 (SD) 随访时间为 1.9 (0.8) 年. 从记忆诊所、临床试验或队列研究中招募了 1431 名参与者;673 人没有认知障碍(CU 组;253 [37. 6%] 淀粉样蛋白-β [Aβ] 阳性),443 人患有轻度认知障碍(MCI 组;271 人 [61.2%] Aβ 阳性),315 人临床诊断为 AD 痴呆(315 [100%] Aβ 阳性)。暴露于发现队列 (n = 1135) 中的 [18F] Flortaucipir PET 或复制队列 (n = 296) 中的 [18F] RO948 PET、T1 加权 MRI (n = 1431) 和淀粉样蛋白 PET (n = 1329)基线和重复的简易精神状态检查 (MMSE) 评估。主要结果和测量基线 [18F]flortaucipir/[18F]RO948 PET 保留在感兴趣的颞叶区域内、基于 MRI 的 AD 特征皮层厚度和淀粉样蛋白 PET Centiloids 用于使用调整的线性混合效应模型预测 MMSE 的变化年龄、性别、教育和队列。中介/相互作用分析测试了基线 tau PET 与认知变化之间的关联是否由基线 MRI 测量介导,以及年龄、性别和 APOE 基因型是否改变了这些关联。结果 在 1431 名参与者中,平均 (SD) 年龄为 71.2 (8.8) 岁;751 (52.5%) 人为男性。[18F]flortaucipir PET 的结果预测了 MMSE 的纵向变化,并且所有参与者的效应大小都强于 AD 特征皮层厚度和淀粉样蛋白 PET(R2,0.35 [tau PET] vs 0.24 [MRI] vs 0.17 [淀粉样蛋白 PET] ;P < .001,差异自举)在 Aβ 阳性 MCI 组(R2,0.25 [tau PET] vs 0.15 [MRI] vs 0.07 [淀粉样蛋白 PET];P < .001,差异自举)和 Aβ - 阳性 CU 组(R2,0.16 [tau PET] vs 0.08 [MRI] vs 0.08 [amyloid PET];P < .001,差异自举)。这些发现在 [18F]RO948 PET 队列中得到了复制。MRI 介导了 [18F]flortaucipir PET 和 MMSE 在 AD 痴呆组(占总效应的 33.4% [95% CI,15.5%-60.0%])和 Aβ 阳性 MCI(13.6% [95% CI, 0.0%-28.0%] 的总效应),但不是 Aβ 阳性 CU 组(3.7% [95% CI,-17.5% 至 39.0%];P = .71)。年龄 (t = -2.28; P = .02),但性别 (t = 0.92; P = .36) 或 APOE 基因型 (t = 1.06; P = .29) 改变了基线 [18F]flortaucipir PET 和认知变化,因此老年人在相似的 tau PET 水平下表现出更快的认知衰退。
更新日期:2021-06-28
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