Fibre-specific white matter reductions in Alzheimer's disease and mild cognitive impairment
Fibre-specific white matter reductions in Alzheimer's disease and mild cognitive impairment
复制标题
阿尔茨海默病和轻度认知障碍的纤维特异性白质减少
DOI：
10.1093/brain/awx355
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发表时间：
2018-03-01
期刊：
影响因子：
14.5
通讯作者：
Connelly, Alan
中科院分区：
文献类型：
--
作者：
Mito, Remika;Raffelt, David;Connelly, Alan
阿尔茨海默病越来越被认为是一种大规模网络断开综合征，与病理蛋白质的进行性聚集、皮质萎缩和脑区域之间的功能断开有关。这些病理变化被认为是以一种刻板的时空方式出现的，目标是大脑中的内在网络，最明显的是默认模式网络。虽然这种网络特定的中断已被彻底研究与功能神经成像，大脑的结构网络内的特定的白色物质纤维通路的变化还没有密切调查，主要是由于复杂的白色物质结构建模的挑战。在这里，我们应用了一种称为“基于固定的分析”的新技术，在体素内水平（称为“固定”）全面研究纤维束特异性差异，以评估阿尔茨海默病和轻度认知障碍受试者的潜在轴突损失。我们假设，阿尔茨海默病患者将在连接默认网络节点的关键纤维通路上表现出广泛的变性，而轻度认知障碍患者将在连接先前被确定为在阿尔茨海默病早期功能上涉及的区域的纤维通路内表现出选择性变性。阿尔茨海默病（n = 49），轻度认知障碍（n = 33），和健康的老年对照组（n = 95）的扩散MRI数据来自澳大利亚成像，生物标志物和生活方式的老化研究。我们评估了纤维密度的微观结构差异，和纤维束形态的宏观结构差异，使用fixelbased分析。进行全脑分析以比较所有白色物质固定的组。随后，我们进行了一个感兴趣的束分析，比较了11个选定的白色束的纤维密度和横截面，以研究轻度认知障碍中纤维通路内潜在的微妙变性，最初仅通过临床诊断，然后通过包括淀粉样蛋白状态（即，e.阳性或阴性淀粉样蛋白PET扫描）。我们的全脑分析揭示了显着的白色物质损失表现在阿尔茨海默病患者的微观结构和宏观结构，明显的特定纤维通路与默认模式网络节点。当统计分析仅限于感兴趣的神经束时，轻度认知障碍患者的纤维密度和横截面减少仅在后扣带回内表现出。有趣的是，这些退行性变化似乎与高淀粉样蛋白积聚无关，因为淀粉样蛋白阴性而非阳性的轻度认知障碍受试者表现出轻微的局灶性左后扣带缺陷。这项研究的结果表明，阿尔茨海默病患者的白色变性的刻板分布，这与其他成像方式的典型结果一致，并与基于网络的疾病概念化。
Alzheimer's disease is increasingly considered a large-scale network disconnection syndrome, associated with progressive aggregation of pathological proteins, cortical atrophy, and functional disconnections between brain regions. These pathological changes are posited to arise in a stereotypical spatiotemporal manner, targeting intrinsic networks in the brain, most notably the default mode network. While this network-specific disruption has been thoroughly studied with functional neuroimaging, changes to specific white matter fibre pathways within the brain's structural networks have not been closely investigated, largely due to the challenges of modelling complex white matter structure. Here, we applied a novel technique known as ` fixel-based analysis' to comprehensively investigate fibre tract-specific differences at a within-voxel level (called ` fixels') to assess potential axonal loss in subjects with Alzheimer's disease and mild cognitive impairment. We hypothesized that patients with Alzheimer's disease would exhibit extensive degeneration across key fibre pathways connecting default network nodes, while patients with mild cognitive impairment would exhibit selective degeneration within fibre pathways connecting regions previously identified as functionally implicated early in Alzheimer's disease. Diffusion MRI data from Alzheimer's disease (n = 49), mild cognitive impairment (n = 33), and healthy elderly control subjects (n = 95) were obtained from the Australian Imaging, Biomarkers and Lifestyle study of ageing. We assessed microstructural differences in fibre density, and macrostructural differences in fibre bundle morphology using fixelbased analysis. Whole-brain analysis was performed to compare groups across all white matter fixels. Subsequently, we performed a tract of interest analysis comparing fibre density and cross-section across 11 selected white matter tracts, to investigate potentially subtle degeneration within fibre pathways in mild cognitive impairment, initially by clinical diagnosis alone, and then by including amyloid status (i. e. a positive or negative amyloid PET scan). Our whole-brain analysis revealed significant white matter loss manifesting both microstructurally and macrostructurally in Alzheimer's disease patients, evident in specific fibre pathways associated with default mode network nodes. Reductions in fibre density and cross-section in mild cognitive impairment patients were only exhibited within the posterior cingulum when statistical analyses were limited to tracts of interest. Interestingly, these degenerative changes did not appear to be associated with high amyloid accumulation, given that amyloid-negative, but not positive, mild cognitive impairment subjects exhibited subtle focal left posterior cingulum deficits. The findings of this study demonstrated a stereotypical distribution of white matter degeneration in patients with Alzheimer's disease, which was in line with canonical findings from other imaging modalities, and with a network-based conceptualization of the disease.