Associations between white matter microstructure and amyloid burden in preclinical Alzheimer's disease: A multimodal imaging investigation.
Associations between white matter microstructure and amyloid burden in preclinical Alzheimer's disease: A multimodal imaging investigation.
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DOI：
10.1016/j.nicl.2014.02.001
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Johnson SC
中科院分区：
文献类型：
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作者：
Racine AM;Adluru N;Alexander AL;Christian BT;Okonkwo OC;Oh J;Cleary CA;Birdsill A;Hillmer AT;Murali D;Barnhart TE;Gallagher CL;Carlsson CM;Rowley HA;Dowling NM;Asthana S;Sager MA;Bendlin BB;Johnson SC
一些认知健康的个体出现脑淀粉样蛋白积聚，提示可能患有早期阿尔茨海默病（AD），但淀粉样蛋白对其他可能提供信息的成像方式（如弥散张量成像（DTI））在表征临床前AD的脑部变化方面的影响需要进一步探索。在这项研究中，从威斯康星州阿尔茨海默病预防登记处（WRAP）招募了一个样本（N = 139，平均年龄60.6岁，范围46 - 71岁），该队列富含AD风险因素，用于一项包括DTI和[C - 11]匹兹堡化合物B（PiB）正电子发射断层扫描（PET）的多模态成像研究。参与者根据淀粉样蛋白沉积的数量和模式分为淀粉样蛋白阳性（Aβ +）、淀粉样蛋白不确定（Aβi）或淀粉样蛋白阴性（Aβ -）组。对四个DTI指标，即分数各向异性（FA）、平均弥散率（MD）、轴向弥散率（Da）和径向弥散率（Dr）进行了基于淀粉样蛋白分组的区域体素分析。根据其在AD早期阶段的参与情况，选择了三个感兴趣区域（ROI），即紧邻胼胝体的扣带、海马扣带和外侧穹窿。体素分析显示，在所有三个ROI中，Aβ +组的FA高于Aβ -组，在紧邻胼胝体的扣带中，Aβi组的FA高于Aβ -组。后续的探索性全脑分析与ROI结果一致，揭示了多个FA较高与淀粉样蛋白较多相关的区域。较低的额颞叶灰质MD与较高的淀粉样蛋白负荷相关。进一步研究表明MD与PiB信号呈负相关，提示Aβ积聚损害弥散。有趣的是，在这个主要是无症状样本中的这些发现与文献中关于轻度认知障碍和AD有症状疾病阶段所报道的关系相反，后者通常显示MD较高而FA较低。结合分析表明这些参与者的认知功能与四个DTI指标中的任何一个都不相关，目前的结果提示PiB和DTI之间的早期关系，这可能是认知下降之前AD的起始或代偿机制的一个有意义的指标。
阿尔茨海默病临床前受试者研究队列（N = 139）
基于整体淀粉样蛋白负荷对三组的四个DTI指标进行检查
较高的淀粉样蛋白负荷与较高的分数各向异性相关。
额颞叶灰质的弥散率与淀粉样蛋白呈负相关。
在这个疾病早期阶段，DTI指标与认知无关。
Some cognitively healthy individuals develop brain amyloid accumulation, suggestive of incipient Alzheimer's disease (AD), but the effect of amyloid on other potentially informative imaging modalities, such as Diffusion Tensor Imaging (DTI), in characterizing brain changes in preclinical AD requires further exploration. In this study, a sample (N = 139, mean age 60.6, range 46 to 71) from the Wisconsin Registry for Alzheimer's Prevention (WRAP), a cohort enriched for AD risk factors, was recruited for a multimodal imaging investigation that included DTI and [C-11]Pittsburgh Compound B (PiB) positron emission tomography (PET). Participants were grouped as amyloid positive (Aβ+), amyloid indeterminate (Aβi), or amyloid negative (Aβ−) based on the amount and pattern of amyloid deposition. Regional voxel-wise analyses of four DTI metrics, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da), and radial diffusivity (Dr), were performed based on amyloid grouping. Three regions of interest (ROIs), the cingulum adjacent to the corpus callosum, hippocampal cingulum, and lateral fornix, were selected based on their involvement in the early stages of AD. Voxel-wise analysis revealed higher FA among Aβ+ compared to Aβ− in all three ROIs and in Aβi compared to Aβ− in the cingulum adjacent to the corpus callosum. Follow-up exploratory whole-brain analyses were consistent with the ROI findings, revealing multiple regions where higher FA was associated with greater amyloid. Lower fronto-lateral gray matter MD was associated with higher amyloid burden. Further investigation showed a negative correlation between MD and PiB signal, suggesting that Aβ accumulation impairs diffusion. Interestingly, these findings in a largely presymptomatic sample are in contradistinction to relationships reported in the literature in symptomatic disease stages of Mild Cognitive Impairment and AD, which usually show higher MD and lower FA. Together with analyses showing that cognitive function in these participants is not associated with any of the four DTI metrics, the present results suggest an early relationship between PiB and DTI, which may be a meaningful indicator of the initiating or compensatory mechanisms of AD prior to cognitive decline. Study cohort of preclinical subjects (N = 139) at risk for Alzheimer's disease Examination of four DTI metrics in three groups based on global amyloid load Greater amyloid load was associated with higher fractional anisotropy. Diffusivity was negatively associated with amyloid in fronto-lateral gray matter. DTI metrics were not correlated with cognition at this early disease stage.