Contribution of iron and Aβ to age differences in entorhinal and hippocampal subfield volume.
Contribution of iron and Aβ to age differences in entorhinal and hippocampal subfield volume.
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DOI：
10.1212/wnl.0000000000010868
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发表时间：
2020-11-03
期刊：
影响因子：
9.9
通讯作者：
Rodrigue KM
中科院分区：
文献类型：
--
作者：
Foster CM;Kennedy KM;Daugherty AM;Rodrigue KM
为了验证这一假设，即整体β-淀粉样蛋白（Aβ）负荷升高和纹状体铁含量增加的组合与内嗅皮层（ERC）体积较小相关，但与海马子域体积无关，我们在70名认知正常的老年人的横断面样本中使用高分辨率MRI测量体积和铁含量，并使用PET成像测量Aβ。使用florbetapir 18F PET扫描参与者，以获得Aβ标准化摄取值比值。收集磁敏感加权MRI并处理以产生R2* 图像，并手动放置纹状体感兴趣区域（ROI）以获得纹状体铁负荷的测量值。对超高分辨率T2/PD加权MRI进行分段，以测量内侧颞叶（MTL）体积。使用混合效应模型进行分析，其中MTL ROI作为参与者内因素;年龄、铁含量和Aβ作为参与者间因素; MTL体积（ERC和3个海马子区）作为因变量。模型显示年龄、铁、Aβ和MTL区域之间存在显著的4向交互作用。事后分析表明，年龄、Aβ和铁含量之间的3向相互作用对ERC具有选择性（β = −3.34，标准误= 1.33，95%置信区间−5.95至−0.72），而年龄和ERC体积之间的显著负相关仅存在于铁含量和Aβ均升高的个体中。这些发现强调了在其他可能协同的年龄相关脑因素（如铁积累）的背景下研究Aβ的重要性，以及铁作为病理性衰老的最早临床前阶段的重要贡献者的潜在作用。
To test the hypothesis that the combination of elevated global β-AMYLOID (Aβ) burden and greater striatal iron content would be associated with smaller entorhinal cortex (ERC) volume, but not hippocampal subfield volumes, we measured volume and iron content using high-resolution MRI and Aβ using PET imaging in a cross-sectional sample of 70 cognitively normal older adults. Participants were scanned with florbetapir 18F PET to obtain Aβ standardized uptake value ratios. Susceptibility-weighted MRI was collected and processed to yield R2* images, and striatal regions of interest (ROIs) were manually placed to obtain a measure of striatal iron burden. Ultra-high resolution T2/PD-weighted MRIs were segmented to measure medial temporal lobe (MTL) volumes. Analyses were conducted using mixed-effects models with MTL ROI as a within-participant factor; age, iron content, and Aβ as between-participant factors; and MTL volumes (ERC and 3 hippocampal subfield regions) as the dependent variable. The model indicated a significant 4-way interaction among age, iron, Aβ, and MTL region. Post hoc analyses indicated that the 3-way interaction among age, Aβ, and iron content was selective to the ERC (β = −3.34, standard error = 1.33, 95% confidence interval −5.95 to −0.72), whereas a significant negative association between age and ERC volume was present only in individuals with both elevated iron content and Aβ. These findings highlight the importance of studying Aβ in the context of other, potentially synergistic age-related brain factors such as iron accumulation and the potential role for iron as an important contributor to the earliest, preclinical stages of pathologic aging.