Neuro-degeneration profile of Alzheimer's patients: A brain morphometry study.
Neuro-degeneration profile of Alzheimer's patients: A brain morphometry study.
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DOI：
10.1016/j.nicl.2017.04.001
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发表时间：
2017
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影响因子：
--
通讯作者：
Moriguti JC
中科院分区：
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作者：
Ramos Bernardes da Silva Filho S;Oliveira Barbosa JH;Rondinoni C;Dos Santos AC;Garrido Salmon CE;da Costa Lima NK;Ferriolli E;Moriguti JC
阿尔茨海默病（Alzheimer's disease，AD）是一种以认知功能减退和记忆障碍为特征的原发性、进行性神经退行性疾病。海马和其他基底脑区的萎缩是与AD相关的最主要的结构影像学表现之一。大多数研究通过使用磁共振成像的临床试验评估了AD的临床前和初始阶段。尚未对晚期AD阶段的结构生物标志物进行评估，仅假设性地考虑。评估AD患者在所有疾病阶段的脑形态测量学，确定与AD严重程度相关的结构性神经退行性变特征。入选60岁及以上不同AD分期的AD患者，根据临床痴呆评分（CDR）分为3组：CDR 1组（n = 16），CDR 2组（n = 15），CDR 3组（n = 13）。还招募了年龄配对的健康志愿者（n = 16）（对照组）。使用常规梯度eco 3D T1-w序列在3 T磁共振扫描仪上采集脑图像，无需注射造影剂。使用Freesurfer软件通过自动分割获得体积定量数据和皮质厚度。每个脑区的体积通过全脑体积进行标准化，以最小化年龄和身体尺寸的影响。比较各组间的体积和皮质厚度变化。AD患者海马、杏仁核、内嗅皮质、海马旁区、颞极、颞叶等部位均有萎缩。皮质厚度减少，只有在海马旁回在所有的疾病阶段。体积和皮质厚度与所有研究区域的简易精神状态检查（MMSE）评分相关，也与CDR和疾病持续时间相关。如前所述，在其初始阶段受AD影响的脑区域，如海马、杏仁核、内嗅皮层和海马旁区，被发现即使在患有严重AD的个体中也发生改变。此外，个体，特别是具有CDR 3的个体，具有比具有CDR 2的个体更低体积的多个区域。这些结果表明，萎缩率在CDR 2-3处尚未达到稳定，并且在严重患者中仍存在神经元损失和神经胶质增生。这些发现可以为文献中主要集中在早期阶段的更被接受的模型添加重要信息。我们的研究结果允许更好地了解AD的病理生理过程和药物治疗的后续过程，即使在晚期疾病阶段。在所有疾病阶段的阿尔茨海默氏症患者的脑形态测量进行了评估。自动分割和包裹用于量化萎缩。大多数受影响的大脑区域都会萎缩，直到AD晚期（CDR 2-3）才出现平台期。
Alzheimer's disease (AD) is a primary and progressive neurodegenerative disorder, which is marked by cognitive deterioration and memory impairment. Atrophy of hippocampus and other basal brain regions is one of the most predominant structural imaging findings related to AD. Most studies have evaluated the pre-clinical and initial stages of AD through clinical trials using Magnetic Resonance Imaging. Structural biomarkers for advanced AD stages have not been evaluated yet, being considered only hypothetically. To evaluate the brain morphometry of AD patients at all disease stages, identifying the structural neuro-degeneration profile associated with AD severity. AD patients aged 60 years or over at different AD stages were recruited and grouped into three groups following the Clinical Dementia Rating (CDR) score: CDR1 (n = 16), CDR2 (n = 15), CDR3 (n = 13). Age paired healthy volunteers (n = 16) were also recruited (control group). Brain images were acquired on a 3T magnetic resonance scanner using a conventional Gradient eco 3D T1-w sequence without contrast injection. Volumetric quantitative data and cortical thickness were obtained by automatic segmentation using the Freesurfer software. Volume of each brain region was normalized by the whole brain volume in order to minimize age and body size effects. Volume and cortical thickness variations among groups were compared. Atrophy was observed in the hippocampus, amygdala, entorhinal cortex, parahippocampal region, temporal pole and temporal lobe of patients suffering from AD at any stage. Cortical thickness was reduced only in the parahippocampal gyrus at all disease stages. Volume and cortical thickness were correlated with the Mini Mental State Examination (MMSE) score in all studied regions, as well as with CDR and disease duration. As previously reported, brain regions affected by AD during its initial stages, such as hippocampus, amygdala, entorhinal cortex, and parahippocampal region, were found to be altered even in individuals with severe AD. In addition, individuals, specifically, with CDR 3, have multiple regions with lower volumes than individuals with a CDR 2. These results indicate that rates of atrophy have not plateaued out at CDR 2–3, and in severe patients there are yet neuronal loss and gliosis. These findings can add important information to the more accepted model in the literature that focuses mainly on early stages. Our findings allow a better understanding on the AD pathophysiologic process and follow-up process of drug treatment even at advanced disease stages. Brain morphometry of Alzheimer's patients at all disease stages was evaluated. Automatic segmentation and parcellation were used to quantify atrophy. Most affected brain regions suffer atrophy without plateau phase until the later AD stages (CDR 2–3).