Assessment of a Plasma Amyloid Probability Score to Estimate Amyloid Positron Emission Tomography Findings Among Adults With Cognitive Impairment.
Assessment of a Plasma Amyloid Probability Score to Estimate Amyloid Positron Emission Tomography Findings Among Adults With Cognitive Impairment.
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DOI：
10.1001/jamanetworkopen.2022.8392
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发表时间：
2022-04-01
影响因子：
13.8
通讯作者：
West T
中科院分区：
文献类型：
--
作者：
Hu Y;Kirmess KM;Meyer MR;Rabinovici GD;Gatsonis C;Siegel BA;Whitmer RA;Apgar C;Hanna L;Kanekiyo M;Kaplow J;Koyama A;Verbel D;Holubasch MS;Knapik SS;Connor J;Contois JH;Jackson EN;Harpstrite SE;Bateman RJ;Holtzman DM;Verghese PB;Fogelman I;Braunstein JB;Yarasheski KE;West T
淀粉样蛋白概率评分基于质谱血液检测测量血浆淀粉样蛋白β 42：40比率和apoE蛋白型加上年龄，与识别认知障碍患者的脑淀粉样变性相关吗？在这项来自2项独立研究的686名参与者的队列研究中，开发的淀粉样蛋白概率评分显示出与淀粉样蛋白PET状态的高度一致性，曲线下面积为0.88，总体准确性为81%。该测试的结果与正电子发射断层扫描确定的脑淀粉样变性的存在或不存在显著相关。这些发现表明，这种血液检测在检测脑淀粉样变性方面具有强大的性能，可以帮助临床医生诊断认知障碍患者中的阿尔茨海默病。本队列研究评估了与诊断算法相关的临床性能，以估计正电子发射断层扫描（PET）结果中认知障碍成人的脑淀粉样蛋白状态。阿尔茨海默病的诊断评估可以通过基于血液的诊断测试来改善，该测试鉴定脑淀粉样蛋白斑块病理的存在。确定与结合血浆淀粉样蛋白-β（Aβ）42：40比例、患者年龄和apoE蛋白型的诊断算法相关的临床性能，以确定脑淀粉样蛋白状态。本队列研究包括来自2项独立横断面队列研究的分析：淀粉样变性风险筛查血浆检测（巴黎）研究的发现队列，这是成像性痴呆-淀粉样蛋白扫描证据研究的前瞻性附加研究，包括2018年至2019年的249例患者，以及MissionAD，在2016年至2019年的筛查中获得的437份生物库患者样本的数据集。数据分析时间为2020年5月至11月。在血液和正电子发射断层扫描（PET）成像中检测到淀粉样蛋白。主要结局是血浆Aβ42：40比值的诊断性能，以及apoE蛋白型和年龄，用于识别淀粉样蛋白PET状态，通过准确性、灵敏度、特异性和受试者工作特征曲线下面积（AUC）进行评估。所有686名参与者（平均[SD]年龄73.2 [6.3]岁; 368名[53.6%]男性; 378名参与者[55.1%]有淀粉样蛋白PET结果）都有轻度认知障碍或轻度痴呆的症状。巴黎和MissionAD的血浆Aβ42：40比值的AUC分别为0.79（95% CI，0.73-0.85）和0.86（95% CI，0.82-0.89）。基于Youden指数的Aβ42：40比值临界值在队列间相似（巴黎：0.089; MissionAD：0.092）。纳入Aβ42：40比值、apoE蛋白型和年龄的logistic回归模型（LRM）改善了每个队列的诊断性能（巴黎：AUC，0.86 [95% CI，0.81-0.91]; MissionAD：AUC，0.89 [95%CI，0.86-0.92]），巴黎的总体准确性为78%（95%CI，72%-83%），MissionAD的总体准确性为83%（95%CI，79%-86%）。在巴黎前瞻性采集样本上开发的模型在MissionAD样本上表现良好（AUC，0.88 [95% CI，0.84-0.91];准确度，78% [95% CI，74%-82%]）。在联合队列中训练LRM得到的AUC为0.88（95% CI，0.85-0.91），准确度为81%（95% CI，78%-84%）。该LRM的输出是淀粉样蛋白概率评分（APS）。对于临床使用，确定了2个APS临界值，产生3个类别，即脑淀粉样斑块病理学的低、中和高可能性。这些发现表明，这种血液生物标志物测试可以区分脑淀粉样蛋白阳性PET结果的个体与淀粉样蛋白阴性PET结果的个体，并有助于阿尔茨海默病的诊断。
Is an amyloid probability score based on a mass spectrometry–based blood test measuring plasma amyloid β 42:40 ratio and apoE proteotype plus age, associated with identifying brain amyloidosis among patients with cognitive impairment? In this cohort study of 686 participants from 2 separate studies, the developed Amyloid Probability Score showed high concordance with amyloid PET status, with an area under the curve of 0.88 and overall accuracy of 81%. The test’s findings were significantly associated with the presence or absence of brain amyloidosis as determined by positron emission tomography. These findings suggest that this blood test had robust performance in detecting brain amyloidosis and could aid clinicians in the diagnosis of Alzheimer disease among patients with cognitive impairment. This cohort study assesses the clinical performance associated with a diagnostic algorithm to estimate brain amyloid status in positron emission tomography (PET) findings among adults with cognitive impairment. The diagnostic evaluation for Alzheimer disease may be improved by a blood-based diagnostic test identifying presence of brain amyloid plaque pathology. To determine the clinical performance associated with a diagnostic algorithm incorporating plasma amyloid-β (Aβ) 42:40 ratio, patient age, and apoE proteotype to identify brain amyloid status. This cohort study includes analysis from 2 independent cross-sectional cohort studies: the discovery cohort of the Plasma Test for Amyloidosis Risk Screening (PARIS) study, a prospective add-on to the Imaging Dementia–Evidence for Amyloid Scanning study, including 249 patients from 2018 to 2019, and MissionAD, a dataset of 437 biobanked patient samples obtained at screenings during 2016 to 2019. Data were analyzed from May to November 2020. Amyloid detected in blood and by positron emission tomography (PET) imaging. The main outcome was the diagnostic performance of plasma Aβ42:40 ratio, together with apoE proteotype and age, for identifying amyloid PET status, assessed by accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). All 686 participants (mean [SD] age 73.2 [6.3] years; 368 [53.6%] men; 378 participants [55.1%] with amyloid PET findings) had symptoms of mild cognitive impairment or mild dementia. The AUC of plasma Aβ42:40 ratio for PARIS was 0.79 (95% CI, 0.73-0.85) and 0.86 (95% CI, 0.82-0.89) for MissionAD. Ratio cutoffs for Aβ42:40 based on the Youden index were similar between cohorts (PARIS: 0.089; MissionAD: 0.092). A logistic regression model (LRM) incorporating Aβ42:40 ratio, apoE proteotype, and age improved diagnostic performance within each cohort (PARIS: AUC, 0.86 [95% CI, 0.81-0.91]; MissionAD: AUC, 0.89 [95% CI, 0.86-0.92]), and overall accuracy was 78% (95% CI, 72%-83%) for PARIS and 83% (95% CI, 79%-86%) for MissionAD. The model developed on the prospectively collected samples from PARIS performed well on the MissionAD samples (AUC, 0.88 [95% CI, 0.84-0.91]; accuracy, 78% [95% CI, 74%-82%]). Training the LRM on combined cohorts yielded an AUC of 0.88 (95% CI, 0.85-0.91) and accuracy of 81% (95% CI, 78%-84%). The output of this LRM is the Amyloid Probability Score (APS). For clinical use, 2 APS cutoff values were established yielding 3 categories, with low, intermediate, and high likelihood of brain amyloid plaque pathology. These findings suggest that this blood biomarker test could allow for distinguishing individuals with brain amyloid–positive PET findings from individuals with amyloid-negative PET findings and serve as an aid for Alzheimer disease diagnosis.
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影响因子：
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通讯作者：
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影响因子：
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通讯作者：
Rowe CC
影响因子：
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作者：
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