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.
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.
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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。
DOI：
10.1001/jamaneurol.2021.1858
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发表时间：
2021-08-01
期刊：
影响因子：
29
通讯作者：
Hansson O
中科院分区：
文献类型：
--
作者：
Ossenkoppele R;Smith R;Mattsson-Carlgren N;Groot C;Leuzy A;Strandberg O;Palmqvist S;Olsson T;Jögi J;Stormrud E;Cho H;Ryu YH;Choi JY;Boxer AL;Gorno-Tempini ML;Miller BL;Soleimani-Meigooni D;Iaccarino L;La Joie R;Baker S;Borroni E;Klein G;Pontecorvo MJ;Devous MD Sr;Jagust WJ;Lyoo CH;Rabinovici GD;Hansson O
tau正电子发射断层扫描（PET）在预测阿尔茨海默病临床谱中认知功能下降方面的预后价值是什么？在这项包括1431名参与者的纵向、多中心预后研究中，基线tau PET预测了平均（SD）1.9（0.8）年随访期间简易精神状态检查评分的变化。此外，tau PET在头对头比较中优于已建立的体积磁共振成像和淀粉样蛋白PET标记物，特别是在轻度认知障碍的参与者和淀粉样蛋白-β阳性的认知正常个体中。这些发现表明，tau PET是一种有前途的预测阿尔茨海默病临床前和前驱期认知功能下降的预后工具。Tau正电子发射断层扫描（PET）示踪剂已被证明对于痴呆症的鉴别诊断有用，但它们在预测认知变化方面的效用尚不清楚。检查基线氟18（18 F）-flortaucipir和[18 F] RO 948（tau）PET在阿尔茨海默病（AD）临床谱个体中的预后准确性，并与已建立的磁共振成像（MRI）和淀粉样蛋白PET标记物进行头对头比较。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8个队列的数据，平均（SD）随访时间为1.9（0.8）年。共有1431名参与者从记忆诊所、临床试验或队列研究中招募; 673名认知未受损（CU组; 253例[37.6%]淀粉样蛋白β [Aβ]阳性），443例有轻度认知障碍（MCI组; 271例[61.2%] Aβ阳性），315例临床诊断为AD痴呆（315例[100%] Aβ阳性）。发现队列中的[18 F]Flortaucipir PET（n = 1135）或复制队列中的[18 F] RO 948 PET（n = 296）、基线时的T1加权MRI（n = 1431）和淀粉样蛋白PET（n = 1329）以及重复简易精神状态检查（MMSE）评价。使用针对年龄、性别、教育和队列调整的线性混合效应模型，将基线[18 F]flortaucipir/[18 F] RO 948 PET保留在感兴趣的颞区、基于MRI的AD特征皮质厚度和淀粉样蛋白PET Centiloids用于预测MMSE的变化。中介/相互作用分析检测了基线tau PET和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。在1431名参与者中，平均（SD）年龄为71.2（8.8）岁; 751名（52.5%）为男性。在所有参与者中，[18 F]flortaucipir PET的结果可预测MMSE的纵向变化，且效应量强于AD特征皮质厚度和淀粉样蛋白PET（R2，0.35 [tau PET] vs 0.24 [MRI] vs 0.17 [淀粉样蛋白PET]; P <0.001，差异自举），在Aβ阳性MCI组中（R2，0.25 [tau PET] vs 0.15 [MRI] vs 0.07 [淀粉样蛋白PET]; P <0.001，差异自举）和Aβ阳性CU组（R2，0.16 [tau PET] vs 0.08 [MRI] vs 0.08 [淀粉样蛋白PET]; P <0.001，差异自举）。这些发现在[18 F] RO 948 PET队列中得到了重现。MRI介导AD痴呆组中[18 F]flortaucipir PET与MMSE之间的关联（总效应的33.4% [95% CI，15.5%-60.0%]）和Aβ阳性MCI（总效应的13.6% [95% CI，0.0%-28.0%]），但Aβ阳性CU组并非如此（3.7% [95% CI，−17.5%-39.0%]; P = 0.71）。年龄（t =-2.28; P = 0.02），但性别（t = 0.92; P = 0.36）或APOE基因型（t = 1.06; P = 0.29）并未改变基线[18 F]flortaucipir PET与认知变化之间的关联，因此老年人在相似的tau PET水平下表现出更快的认知下降。这项预后研究的结果表明，tau PET是一种有前途的预测认知变化的工具，上级淀粉样蛋白PET和MRI，并可能支持AD临床前和前驱阶段的预后过程。这项预后研究检查了基线[18 F]flortaucipir和[18 F] RO 948（tau）正电子发射断层扫描（PET）在阿尔茨海默病临床谱个体中的预后准确性，并与已建立的磁共振成像和淀粉样蛋白PET标记物进行了头对头比较。
What is the prognostic value of tau positron emission tomography (PET) for predicting cognitive decline across the clinical spectrum of Alzheimer disease? In this longitudinal, multicenter prognostic study including 1431 participants, baseline tau PET predicted change in Mini-Mental State Examination scores during a mean (SD) follow-up of 1.9 (0.8) years. Moreover, tau PET outperformed established volumetric magnetic resonance imaging and amyloid PET markers in head-to-head comparisons, especially in participants with mild cognitive impairment and cognitively normal individuals who were positive for amyloid-β. These findings suggest that tau PET is a promising prognostic tool for predicting cognitive decline in preclinical and prodromal stages of Alzheimer disease. Tau positron emission tomography (PET) tracers have proven useful for the differential diagnosis of dementia, but their utility for predicting cognitive change is unclear. 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. 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). [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. 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. 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. 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. This prognostic study examines the prognostic accuracy of baseline [18F]flortaucipir and [18F]RO948 (tau) positron emission tomography (PET) in individuals across the Alzheimer disease clinical spectrum and performs a head-to-head comparison with established magnetic resonance imaging and amyloid PET markers.
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影响因子：
29
作者：
Leuzy, Antoine;Smith, Ruben;Hansson, Oskar
通讯作者：
Hansson, Oskar
影响因子：
120.7
作者：
Jansen, Willemijn J.;Ossenkoppele, Rik;Knol, Dirk L.;Tijms, Betty M.;Scheltens, Philip;Verhey, Frans R. J.;Visser, Pieter Jelle
通讯作者：
Visser, Pieter Jelle
DOI：
10.1186/s13195-020-00712-4
发表时间：
2020-11-04
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Emrani S;Arain HA;DeMarshall C;Nuriel T
通讯作者：
Nuriel T
影响因子：
5.7
作者：
Bourgeat, Pierrick;Dore, Vincent;Rowe, Christopher C.
通讯作者：
Rowe, Christopher C.
影响因子：
29
作者：
Hanseeuw, Bernard J.;Betensky, Rebecca A.;Johnson, Keith
通讯作者：
Johnson, Keith