基于功能磁共振成像的2型糖尿病患者脑部改变及其与认知功能损害相关性的研究

发布时间：2018-05-31 17:53

本文选题：2型糖尿病 + 认知功能　；参考：《东南大学》2017年博士论文

【摘要】：第一部分:2型糖尿病患者静息态神经元活动的低频振幅和局部一致性异常目的:既往研究显示,2型糖尿病(type 2 diabetes mellitus,T2DM)患者发生认知障碍的风险升高。在认知功能损伤的人群中,其脑部自发性神经活动通常发生异常改变。本研究拟采用静息态磁共振成像技术,研究2型糖尿病患者自发神经活动的变化情况及其与认知障碍的关系。方法:本研究共纳入29例2型糖尿病患者和27例健康志愿者,两组在年龄、性别和教育程度匹配良好。所有被试均行静息态磁共振扫描后,计算得到反映自发性神经活动的两个定量指标,即低频幅度(amplitude of low frequency fluctuation, ALFF)和局部一致性(regional homogeneity, ReHo),同时将这些指标与临床参数进行相关性分析。结果:通过组间比较,我们发现T2DM患者的ALFF明显下降,主要在枕叶脑区和中央后回区域;而ReHo也在同样脑区较对照组下降。更为重要的是,下降的ALFF和ReHo与认知水平的下降具有显著相关性。结论:利用静息态磁共振技术,我们发现T2DM患者脑部自发性神经活动异常,且这种异常改变与神经认知功能水平的下降密切相关。我们的结果可能为T2DM患者发生认知功能障碍的提供了一定的客观依据。第二部分:2型糖尿病患者静息态默认网络功能连接强度的改变目的:静息态默认网络(default mode network,DMN)是维持正常认知功能的重要脑网络,在普通人群中,认知障碍往往伴随DMN完整性的破坏。本研究拟利用独立成分分析的方法,探索T2DM患者默认网络的异常改变及其与认知功能损伤和糖尿病相关临床指标的关系。方法:本研究纳入T2DM患者及健康志愿者各42人。所有被试均行静息态功能磁共振扫描。独立成分分析用于提取静息态默认网络,包括前部(anterior DMN,aDMN)和后部默认网络(posterior DMN,pDMN)两个部分。对两个子网络的功能连接强度进行组间比较,同时也对其与临床指标的关系进行相关分析。结果:与正常组相比,T2DM患者aDMN的功能连接强度升高,尤其是内侧额叶部位,但pDMN功能连接却较正常人显著下降,尤其是后扣带回周围脑区。其中,后扣带回下降的功能连接与复杂图形记忆得分显著相关(r=0.359, p=0.020),与连线测试B耗费时间(r=-0.346,p= 0.025)及胰岛素抵抗水平呈负相关(r=-0.404, p=0.024)。结论:本研究发现,DMN在T2DM患者中呈现出前后部分不一致的改变,这与前期衰老及痴呆相关研究的结果较为一致。这种脑部神经功能连接强度的改变可能为T2DM相关认知功能损伤的发生机制提供一定客观依据。第三部分:2型糖尿病患者全脑功能连接模式的异常改变目的:在第一部分的结果中,我们发现2型糖尿病(type 2 diabetes, T2DM)患者在某些特定脑区的自发性神经元活动发生异常改变,但脑区之间的相互连接是否受到疾病的影响尚未明确。本研究的主要目的是利用静息态功能磁共振成像技术,研究2型糖尿病对全脑功能连接网络结构的影响。方法:本研究包括40例T2DM患者和43例健康志愿者,所有被试行3T磁共振成像进行功能数据采集。对全脑每个体素的功能连接强度进行计算,得到功能连接强度(functional connectivity strength, FCS)指标,并行双样本t检验进行两组间比较。其次,将比较所得的差异脑区设置为种子点,再次进行功能连接计算及组建比较,即从网络层面研究功能连接的改变。最后,利用基于体素水平的相关分析,研究这些差异脑区功能连接变化与认知功能评分的关系。结果:T2DM患者在左侧舌回的功能连接下降,而在右侧岛叶及背侧前扣带回的功能连接升高(校正后P0.05)。进一步基于种子点的功能连接分析发现,左侧舌回与枕叶广泛脑区的功能连接均下降,而以岛叶及扣带回为种子点的网络功能连接(主要为凸显网络)则显著升高)(校正后P0.05)。相关分析发现,病人组在后扣带回的脑血流量在校正前后均与胰岛素抵抗水平呈负相关,且与画钟测试评分呈正相关。另一方面,枕叶的血流量在校正前后均与视觉记忆相关评分呈正相关。结论:T2DM患者全脑功能连接发生异常改变,这说明T2DM对于脑部的影响不仅仅局限于某个特定脑区,而是影响了整个大脑功能连接网络的结构模式。第四部分:2型糖尿病患者脑血流量异常及其与胰岛素抵抗的关系目的:脑血流灌注与认知功能密切相关,且能够更加直观、定量反映脑部生神经元活动的情况。本研究拟利用全脑磁共振动脉自选标记技术,探讨2型糖尿病患者脑血流灌注的改变及其与认知功能损伤的关系。方法:本研究包括40例T2DM患者和41例健康志愿者。所有被试签署知情同意书,并接受认知功能评估。磁共振扫描包括全脑磁共振动脉自选标记序列成像和3D高分辨率T1加权成像。为了去除脑皮质萎缩对灌注的潜在影响,我们引入了部分体积效应校正算法,同时计算校正前和校正后的脑血流灌注值,行双样本t检验两组间比较,并在全脑范围内寻找与认知行为评分和糖尿病指标密切相关的脑灌注区。结果:与对照组相比,T2DM患者的脑血流量在后扣带回、楔前叶及双侧枕叶皮层明显降低(校正后P值0.05)。进行部分体积校正后,这些结果未发生明显改变。相关分析发现,患者后扣带回的脑血流量在校正前后均与胰岛素抵抗水平呈负相关,且与画钟测试评分呈正相关。另一方面,枕叶的血流量在校正前后均与视觉记忆相关评分呈正相关。结论:T2DM患者在认知功能障碍的早期即出现脑血流灌注减低,且减低的形式较痴呆早期相似。更为重要的是,胰岛素抵抗水平增高与这些区域的血流灌注下降相关,预示着胰岛素抵抗可能是T2DM认知障碍发生的重要危险因素和治疗靶点。
[Abstract]:The first part: the low frequency amplitude and local consistency abnormality of resting neuron activity in type 2 diabetic patients: Previous studies have shown that patients with type 2 diabetes (type 2 diabetes mellitus, T2DM) have a higher risk of cognitive impairment. The study was to use resting state magnetic resonance imaging to study the changes of spontaneous neural activity in type 2 diabetic patients and their relationship with cognitive impairment. Methods: This study included 29 patients with type 2 diabetes and 27 healthy volunteers. The two groups matched well with age, sex and education. All subjects performed resting state magnetic resonance scanning. After the tracing, two quantitative indexes reflecting the spontaneous neural activity, namely the amplitude of low frequency fluctuation, ALFF, and the local conformance (regional homogeneity, ReHo), were calculated. At the same time, the correlation between these indexes and the clinical parameters was analyzed. Descending, mainly in the occipital lobe and the central posterior region; and ReHo also decreased in the same brain area than the control group. More importantly, the decrease of ALFF and ReHo had a significant correlation with the decrease of cognitive level. Conclusion: we found the abnormal brain activity in the brain of T2DM patients with resting state magnetic resonance technique, and this abnormal change is with the God. The decline in cognitive function is closely related. Our results may provide a certain objective basis for cognitive impairment in T2DM patients. The second part: the change of the resting state function connection intensity of the resting state of type 2 diabetic patients: the resting state default network (default mode network, DMN) is the maintenance of normal cognitive function. In the general population, cognitive impairment is often associated with the failure of DMN integrity in the general population. This study intends to use the method of independent component analysis to explore the abnormal changes in the default network of T2DM patients and their relationship with cognitive impairment and diabetes related clinical indicators. Methods: This study included 42 people in T2DM and healthy volunteers. The subjects all performed resting state functional magnetic resonance scanning. Independent component analysis was used to extract the resting state default network, including the two parts of the anterior DMN (aDMN) and the default network (posterior DMN, pDMN). The functional connection intensity of the two sub networks was compared between groups, and the relationship between them and clinical indexes was also analyzed. Results: compared with the normal group, the functional connection intensity of aDMN in T2DM patients was higher, especially in the medial frontal lobe, but the functional connection of the pDMN was significantly lower than that of the normal person, especially in the posterior cingulate gyrus. The function connection of the posterior cingulate gyrus was significantly correlated with the complex graphical memory (r=0.359, p=0.020), and the B consumption was tested with the connection. Time (r=-0.346, p= 0.025) and insulin resistance were negatively correlated (r=-0.404, p=0.024). Conclusion: This study found that DMN was partially inconsistent in the patients with T2DM, which was consistent with the results of the early aging and dementia related studies. The changes in the intensity of the brain function connection may be the cognitive work associated with T2DM. The third part: abnormal changes in the whole brain function connection pattern in type 2 diabetic patients: in the first part, we found abnormal changes in spontaneous neuronal activity in some specific brain regions of type 2 diabetes (type 2 diabetes, T2DM), but the phase between the brain regions The main purpose of this study is to study the effect of type 2 diabetes on the structure of the whole brain function connection network using resting state functional magnetic resonance imaging (fMRI). Methods: This study included 40 T2DM patients and 43 healthy volunteers, all of which were tested by 3T magnetic resonance imaging for functional data acquisition. The function connection strength of each voxel in the whole brain is calculated, the function connection strength (functional connectivity strength, FCS) is obtained, and the parallel double sample t test is used to compare the two groups. Secondly, the difference brain regions are set to the seed points, and the work energy connection calculation and formation comparison are carried out again, that is to study the work from the network level. Finally, the correlation analysis based on voxel level was used to study the relationship between functional connectivity changes and cognitive function scores in these differences. Results: functional connections in the left lingual gyrus of T2DM patients decreased and the functional connections in the right island and dorsal cingulate gyrus increased (corrected P0.05). Further based on seed points Functional connection analysis showed that the functional connection between the left lingual gyrus and the occipital lobe decreased, while the network functional connection (mainly the prominent network) in the insula and cingulate gyrus increased significantly (corrected P0.05). The correlation analysis found that the cerebral blood flow of the cingulate gyrus in the patients was all with insulin resistance before and after correction. On the other hand, the blood flow of the occipital lobe is positively correlated with the visual memory correlation score before and after correction. Conclusion: the whole brain function connection of T2DM patients is abnormal, which indicates that the effect of T2DM on the brain is not only limited to a particular brain area, but affects the whole brain function. The fourth part: the abnormal cerebral blood flow in type 2 diabetic patients and their relationship with insulin resistance: the cerebral blood flow is closely related to cognitive function, and it can be more intuitionistic and quantificationally reflect the activity of brain neurons. This study is to use the technique of total brain magnetic resonance angiography to explore type 2 sugar. The changes in cerebral blood flow and their relationship with cognitive impairment in patients with urinary disease. Methods: This study included 40 patients with T2DM and 41 healthy volunteers. All subjects signed informed consent and received cognitive function assessment. MRI scan included total brain magnetic resonance angiography and 3D high resolution T1 weighted imaging. In order to remove the potential effect of cerebral cortical atrophy on perfusion, we introduced a partial volume effect correction algorithm and calculated the pre corrected and corrected cerebral blood flow perfusion values. Double sample t test was used to compare the two groups, and the cerebral perfusion areas closely related to cognitive behavior score and diabetes index were found in the whole brain. Results: with the control group The cerebral blood flow of T2DM patients was significantly reduced in the posterior cingulate gyrus, the anterior cuniate leaf and the bilateral occipital cortex (corrected P value 0.05). After partial volume correction, these results were not significantly changed. On the other hand, the blood flow of the occipital lobe was positively correlated with the visual memory correlation score before and after correction. Conclusion: the decrease of cerebral blood flow in the early stage of cognitive dysfunction in T2DM patients is similar to that in the early stage of dementia. More importantly, the increase of insulin resistance and the blood flow irrigation in these areas are more important. Decreased correlation indicates that insulin resistance may be an important risk factor and therapeutic target for T2DM cognitive impairment.
【学位授予单位】：东南大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R445.2;R587.2;R747.9

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