Entorhinal cortex tau, amyloid-β, cortical thickness and memory performance in non-demented subjects
Entorhinal cortex tau, amyloid-β, cortical thickness and memory performance in non-demented subjects
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DOI：
10.1093/brain/awz025
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发表时间：
2019-04-01
期刊：
影响因子：
14.5
通讯作者：
Jack, Clifford R., Jr.
中科院分区：
文献类型：
--
作者：
Knopman, David S.;Lundt, Emily S.;Jack, Clifford R., Jr.
随着阿尔茨海默病和与年龄相关的大脑疾病的生物标志物越来越多，需要更复杂的分析方法来充分利用它们所传达的信息。大多数工作已经使用分类方法完成，但tau PET，淀粉样PET和皮质厚度在其连续分布中的认知的联合关系尚未得到充分探索。我们在梅奥临床衰老研究中评估了50岁以上的非痴呆受试者，其中2037人接受了3t MRI扫描，985人接受了c -11-匹兹堡化合物B （PIB）和MRI的淀粉样蛋白PET扫描，577人接受了PIB-PET， （18） F-AV1451 flortaucipir PET和MRI。参与者接受了九组认知测试。使用三个测试分数（逻辑记忆延迟回忆、视觉再现延迟回忆和听觉言语学习延迟回忆）生成记忆复合z分数。我们使用梯度增强机模型分析了区域皮质厚度、flortaucipir PET信号、PIB-PET信号与记忆z分数之间的关系。年龄、教育程度、性别和测试暴露次数作为协变量包括在模型中。在这项以非痴呆受试者为基础的人群研究中，大多数生物标志物和记忆z分数之间的关联在70岁之后积累。内嗅皮层在生物标志物和记忆z分数之间表现出最强的相关性。其他颞区也表现出类似但减弱的关联，非颞区在记忆z分数和生物标志物之间的关联可以忽略不计。内嗅flortaucipir PET信号、PIB-PET信号和内嗅皮质厚度与记忆z分数下降有独立和加性相关。与只有非常高的淀粉样蛋白水平与低记忆z分数相关的整体PIB-PET信号相反，仅高于背景水平的内嗅flortaucipir PET信号与低记忆z分数相关。记忆z分数最低的是高flortaucipir PET信号和低嗅皮质厚度的汇合。
As more biomarkers for Alzheimer's disease and age-related brain conditions become available, more sophisticated analytic approaches are needed to take full advantage of the information they convey. Most work has been done using categorical approaches but the joint relationships of tau PET, amyloid PET and cortical thickness in their continuous distributions to cognition have been under-explored. We evaluated non-demented subjects over age 50 years in the Mayo Clinic Study of Aging, 2037 of whom had undergone 3 T MRI scan, 985 amyloid PET scan with C-11-Pittsburgh compound B (PIB) and MRI, and 577 PIB-PET, (18) F-AV1451 flortaucipir PET and MRI. Participants received a nine-test cognitive battery. Three test scores (logical memory delayed recall, visual reproduction delayed recall and auditory verbal learning test delayed recall) were used to generate a memory composite z-score. We used Gradient Boosting Machine models to analyse the relationship between regional cortical thickness, flortaucipir PET signal, PIB-PET signal and memory z-scores. Age, education, sex and number of test exposures were included in the model as covariates. In this population-based study of non-demented subjects, most of the associations between biomarkers and memory z-scores accrued after 70 years of age. Entorhinal cortex exhibited the strongest associations between biomarkers and memory z-scores. Other temporal regions showed similar but attenuated associations, and non-temporal regions had negligible associations between memory z-scores and biomarkers. Entorhinal flortaucipir PET signal, PIB-PET signal and entorhinal cortical thickness were independently and additively associated with declining memory z-scores. In contrast to global PIB-PET signal where only very high amyloid-beta levels were associated low memory z-scores, entorhinal flortaucipir PET signal just above background levels was associated with low memory z-scores. The lowest memory z-scores occurred with the confluence of elevated entorhinal flortaucipir PET signal and lower entorhinal cortical thickness.