Diagnostic Performance of RO948 F 18 Tau Positron Emission Tomography in the Differentiation of Alzheimer Disease From Other Neurodegenerative Disorders
Diagnostic Performance of RO948 F 18 Tau Positron Emission Tomography in the Differentiation of Alzheimer Disease From Other Neurodegenerative Disorders
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DOI：
10.1001/jamaneurol.2020.0989
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发表时间：
2020-08-01
期刊：
影响因子：
29
通讯作者：
Hansson, Oskar
中科院分区：
文献类型：
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作者：
Leuzy, Antoine;Smith, Ruben;Hansson, Oskar
问题：与磁共振成像和脑脊液测量相比，RO 948 F 18正电子发射断层扫描如何区分阿尔茨海默病和其他神经退行性疾病？结果在这项诊断性研究中，包括613例来自瑞典BioFINDER-2临床试验的患者，与认知未受损的对照组和其他神经退行性疾病患者相比，阿尔茨海默病痴呆患者的RO 948 F 18标准摄取值比率较高;此外，RO 948 F 18优于磁共振成像和脑脊液测量。一般来说，tau正电子发射断层扫描阳性仅限于该队列中的淀粉样蛋白β阳性病例或MAPT R406 W突变携带者;在语义变异型原发性进行性失语症患者中，RO 948 F18保留率低于flortaucipir F18。这些发现表明，RO 948 F 18对阿尔茨海默病型tau蛋白具有高度特异性，并突出了其作为记忆诊所治疗患者的诊断标志物的潜力。重要性第二代tau蛋白正电子发射断层扫描（PET）示踪剂的诊断性能尚不清楚。目的研究新型tau蛋白PET示踪剂RO 948 F18（[F-18] RO 948）在阿尔茨海默病（AD）与非AD神经退行性疾病鉴别诊断中的作用。在这项诊断研究中，瑞典BioFINDER-2研究的613名参与者从2017年9月4日至2019年8月28日连续入组了一项前瞻性横断面研究。参与者包括257名认知未受损的对照组，154名轻度认知障碍患者，100名AD痴呆患者和102名非AD神经退行性疾病患者。评价包括tau PET示踪剂[F-18] RO 948与磁共振成像（MRI）和脑脊液的比较，以及[F-18] RO 948和flortaucipir F 18（[F-18]flortaucipir）在语义变异型原发性进行性失语症（svPPA）患者中的头对头比较。暴露[F-18] RO 948（所有患者）和[F-18]flortaucipir（3例svPPA患者）tau PET; MRI（海马体积、复合颞叶皮质厚度、全脑皮质厚度）和脑脊液测量（p-tau 181和淀粉样蛋白A β 42和A β 40比值[A β 42/A β 40]和A β 42/p-tau 181比值）。4个预定义感兴趣区域（ROI）中的标准摄取值比率（SUVR），反映了tau病理学的Braak分期方案，包括I-II（内嗅皮层），III-IV（颞下/中、梭状回、海马旁皮质和杏仁核）、I-IV和V-VI（广泛的新皮层区域）、受试者工作特征曲线（AUC）值下的面积以及[F-18] RO 948和[F-18]flortaucipir之间的减影图像。结果613名参与者中的诊断组包括认知未受损的（平均[SD]年龄，65.8 [12.1]岁; 117例男性[46%]），轻度认知障碍（年龄，70.8 [8.3]岁; 82名男性[53%]）、AD痴呆（年龄，73.5 [6.7]岁; 57名男性[57%]）和非AD疾病（年龄，70.5 [8.6]岁; 41名男性[40%]）。与所有其他诊断组相比，AD痴呆患者的[F-18] RO 948保留率更高。[F-18] RO 948可以区分AD痴呆患者与无认知障碍的个体和非AD疾病患者，使用I-IV ROI获得的AUC最高（AUC = 0.98; 95% CI，AD与无认知障碍相比为0.96-0.99，AUC = 0.97; AD vs非AD疾病的95% CI，0.95-0.99），其优于MRI（使用全脑厚度，AD与无认知障碍的最高AUC = 0.91，AD与非AD疾病的AUC = 0.80，使用颞叶厚度）和脑脊液测量（使用A β 42/p-tau 181，AD与无认知障碍的最高AUC = 0.94，使用A β 42/A β 40，AD与非AD疾病的最高AUC = 0.93）。通常，仅在A β阳性病例或MAPT R406 W突变携带者中观察到使用[F-18] RO 948的tau PET阳性。svPPA患者中[F-18] RO 948的保留不明显，头对头比较显示颞叶摄取低于[F-18]flortaucipir。结论和相关性在这项研究中，[F-18] RO 948 SUVR升高最常见于A β阳性病例，提示[F-18] RO 948对AD具有高度特异性，tau型，并强调其作为AD鉴别诊断中诊断标记物的潜力。这项诊断研究探讨了RO 948 F 18在tau正电子发射断层成像中作为AD诊断标记物的用途。与磁共振成像和脑脊液测量相比，阿尔茨海默病的识别。
Question How does RO948 F 18 positron emission tomographic scanning discriminate between Alzheimer disease and other neurodegenerative disorders in comparison with magnetic resonance imaging and cerebrospinal fluid measures? Findings In this diagnostic study including 613 patients from the Swedish BioFINDER-2 clinical trial, standard uptake value ratios of RO948 F 18 were higher in patients with Alzheimer disease dementia compared with cognitively unimpaired controls and patients with other neurodegenerative disorders; furthermore, RO948 F 18 outperformed magnetic resonance imaging and cerebrospinal fluid measures. Generally, tau positron emission tomographic positivity was confined to amyloid beta-positive cases or MAPT R406W mutation carriers in this cohort; in patients with semantic variant primary progressive aphasia, RO948 F 18 retention was lower than that for flortaucipir F 18. Meaning These findings suggest that RO948 F 18 has a high specificity for Alzheimer disease-type tau and highlight its potential as a diagnostic marker in the workup of patients treated in memory clinics.Importance The diagnostic performance of second-generation tau positron emission tomographic (PET) tracers is not yet known. Objective To examine the novel tau PET tracer RO948 F 18 ([F-18]RO948) performance in discriminating Alzheimer disease (AD) from non-AD neurodegenerative disorders. Design, Setting, and Participants In this diagnostic study, 613 participants in the Swedish BioFINDER-2 study were consecutively enrolled in a prospective cross-sectional study from September 4, 2017, to August 28, 2019. Participants included 257 cognitively unimpaired controls, 154 patients with mild cognitive impairment, 100 patients with AD dementia, and 102 with non-AD neurodegenerative disorders. Evaluation included a comparison of tau PET tracer [F-18]RO948 with magnetic resonance imaging (MRI) and cerebrospinal fluid and a head-to-head comparison between [F-18]RO948 and flortaucipir F 18 ([F-18]flortaucipir) in patients with semantic variant primary progressive aphasia (svPPA). Exposures [F-18]RO948 (all patients) and [F-18]flortaucipir (3 patients with svPPA) tau PET; MRI (hippocampal volume, composite temporal lobe cortical thickness, whole-brain cortical thickness) and cerebrospinal fluid measures (p-tau181 and amyloid A beta 42 and A beta 40 ratio[A beta 42/A beta 40], and A beta 42/p-tau181 ratio). Main Outcomes and Measures Standard uptake value ratios (SUVRs) in 4 predefined regions of interest (ROIs) reflecting Braak staging scheme for tau pathology and encompass I-II (entorhinal cortex), III-IV (inferior/middle temporal, fusiform gyrus, parahippocampal cortex, and amygdala), I-IV, and V-VI (widespread neocortical areas), area under the receiver operating characteristic curve (AUC) values, and subtraction images between [F-18]RO948 and [F-18]flortaucipir. Results Diagnostic groups among the 613 participants included cognitively unimpaired (mean [SD] age, 65.8 [12.1] years; 117 men [46%]), mild cognitive impairment (age, 70.8 [8.3] years; 82 men [53%]), AD dementia (age, 73.5 [6.7] years; 57 men [57%]), and non-AD disorders (age, 70.5 [8.6] years; 41 men [40%]). Retention of [F-18]RO948 was higher in AD dementia compared with all other diagnostic groups. [F-18]RO948 could distinguish patients with AD dementia from individuals without cognitive impairment and those with non-AD disorders, and the highest AUC was obtained using the I-IV ROI (AUC = 0.98; 95% CI, 0.96-0.99 for AD vs no cognitive impairment and AUC = 0.97; 95% CI, 0.95-0.99 for AD vs non-AD disorders), which outperformed MRI (highest AUC = 0.91 for AD vs no cognitive impairment using whole-brain thickness, and AUC = 0.80 for AD vs non-AD disorders using temporal lobe thickness) and cerebrospinal fluid measures (highest AUC = 0.94 for AD vs no cognitive impairment using A beta 42/p-tau181, and AUC = 0.93 for AD vs non-AD disorders using A beta 42/A beta 40). Generally, tau PET positivity using [F-18]RO948 was observed only in A beta-positive cases or in MAPT R406W mutation carriers. Retention of [F-18]RO948 was not pronounced in patients with svPPA, and head-to-head comparison revealed lower temporal lobe uptake than with [F-18]flortaucipir. Conclusions and Relevance In this study, elevated [F-18]RO948 SUVRs were most often seen among A beta-positive cases, which suggests that [F-18]RO948 has high specificity for AD-type tau and highlights its potential as a diagnostic marker in the differential diagnosis of AD.This diagnostic study examines the use of RO948 F 18 in tau positron emission tomographic imaging as a diagnostic marker for identification of Alzheimer disease compared with magnetic resonance imaging and cerebrospinal fluid measures.