Individualized prognosis of cognitive decline and dementia in mild cognitive impairment based on plasma biomarker combinations
Individualized prognosis of cognitive decline and dementia in mild cognitive impairment based on plasma biomarker combinations
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DOI：
10.1038/s43587-020-00003-5
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发表时间：
2021-01-01
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影响因子：
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通讯作者：
Hansson, Oskar
中科院分区：
文献类型：
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作者：
Cullen, Nicholas C.;Leuzy, Antoine;Hansson, Oskar
我们开发了使用β-淀粉样蛋白(Aβ)、tau和神经变性的血浆生物标记物预测轻度认知障碍(MCI)认知功能下降的个体化风险模型。来自瑞典BioFINDER研究和阿尔茨海默病神经成像倡议(ADNI)的573名MCI患者被纳入研究。主要结果是纵向认知和转化为阿尔茨海默病(AD)痴呆。在所有模型中，结合苏氨酸181位的tau磷酸化(P-tau181)和神经细丝光(NFL)，而不是Aβ(42)/A beta(40)的模型具有最好的预后性能(在BioFINDER中，4年转换为AD的曲线下面积=0.88，在ADNI中得到验证)，比年龄、性别、教育程度和基线认知的基本模型更强，表现与脑脊液生物标志物相似。介绍了一种基于我们的联合血浆生物标记物模型的MCI个体化预后在线工具。在临床试验和临床实践中，血浆生物标记物的联合应用可能对识别将进展为AD痴呆的MCI个体具有很高的价值。
We developed models for individualized risk prediction of cognitive decline in mild cognitive impairment (MCI) using plasma biomarkers of beta-amyloid (A beta), tau and neurodegeneration. A total of 573 patients with MCI from the Swedish BioFINDER study and the Alzheimer's Disease Neuroimaging Initiative (ADNI) were included in the study. The primary outcomes were longitudinal cognition and conversion to Alzheimer's disease (AD) dementia. A model combining tau phosphorylated at threonine 181 (P-tau181) and neurofilament light (NfL), but not A beta(42)/A beta(40), had the best prognosis performance of all models (area under the curve=0.88 for 4-year conversion to AD in BioFINDER, validated in ADNI), was stronger than a basic model of age, sex, education and baseline cognition, and performed similarly to cerebrospinal fluid biomarkers. A publicly available online tool for individualized prognosis in MCI based on our combined plasma biomarker models is introduced. Combination of plasma biomarkers may be of high value to identify individuals with MCI who will progress to AD dementia in clinical trials and in clinical practice.