本文選題：2型糖尿病 + 認(rèn)知功能��； 參考：《東南大學(xué)》2017年博士論文

【摘要】：第一部分:2型糖尿病患者靜息態(tài)神經(jīng)元活動(dòng)的低頻振幅和局部一致性異常目的:既往研究顯示,2型糖尿病(type 2 diabetes mellitus,T2DM)患者發(fā)生認(rèn)知障礙的風(fēng)險(xiǎn)升高。在認(rèn)知功能損傷的人群中,其腦部自發(fā)性神經(jīng)活動(dòng)通常發(fā)生異常改變。本研究擬采用靜息態(tài)磁共振成像技術(shù),研究2型糖尿病患者自發(fā)神經(jīng)活動(dòng)的變化情況及其與認(rèn)知障礙的關(guān)系。方法:本研究共納入29例2型糖尿病患者和27例健康志愿者,兩組在年齡、性別和教育程度匹配良好。所有被試均行靜息態(tài)磁共振掃描后,計(jì)算得到反映自發(fā)性神經(jīng)活動(dòng)的兩個(gè)定量指標(biāo),即低頻幅度(amplitude of low frequency fluctuation, ALFF)和局部一致性(regional homogeneity, ReHo),同時(shí)將這些指標(biāo)與臨床參數(shù)進(jìn)行相關(guān)性分析。結(jié)果:通過(guò)組間比較,我們發(fā)現(xiàn)T2DM患者的ALFF明顯下降,主要在枕葉腦區(qū)和中央后回區(qū)域;而ReHo也在同樣腦區(qū)較對(duì)照組下降。更為重要的是,下降的ALFF和ReHo與認(rèn)知水平的下降具有顯著相關(guān)性。結(jié)論:利用靜息態(tài)磁共振技術(shù),我們發(fā)現(xiàn)T2DM患者腦部自發(fā)性神經(jīng)活動(dòng)異常,且這種異常改變與神經(jīng)認(rèn)知功能水平的下降密切相關(guān)。我們的結(jié)果可能為T(mén)2DM患者發(fā)生認(rèn)知功能障礙的提供了一定的客觀依據(jù)。第二部分:2型糖尿病患者靜息態(tài)默認(rèn)網(wǎng)絡(luò)功能連接強(qiáng)度的改變目的:靜息態(tài)默認(rèn)網(wǎng)絡(luò)(default mode network,DMN)是維持正常認(rèn)知功能的重要腦網(wǎng)絡(luò),在普通人群中,認(rèn)知障礙往往伴隨DMN完整性的破壞。本研究擬利用獨(dú)立成分分析的方法,探索T2DM患者默認(rèn)網(wǎng)絡(luò)的異常改變及其與認(rèn)知功能損傷和糖尿病相關(guān)臨床指標(biāo)的關(guān)系。方法:本研究納入T2DM患者及健康志愿者各42人。所有被試均行靜息態(tài)功能磁共振掃描。獨(dú)立成分分析用于提取靜息態(tài)默認(rèn)網(wǎng)絡(luò),包括前部(anterior DMN,aDMN)和后部默認(rèn)網(wǎng)絡(luò)(posterior DMN,pDMN)兩個(gè)部分。對(duì)兩個(gè)子網(wǎng)絡(luò)的功能連接強(qiáng)度進(jìn)行組間比較,同時(shí)也對(duì)其與臨床指標(biāo)的關(guān)系進(jìn)行相關(guān)分析。結(jié)果:與正常組相比,T2DM患者aDMN的功能連接強(qiáng)度升高,尤其是內(nèi)側(cè)額葉部位,但pDMN功能連接卻較正常人顯著下降,尤其是后扣帶回周圍腦區(qū)。其中,后扣帶回下降的功能連接與復(fù)雜圖形記憶得分顯著相關(guān)(r=0.359, p=0.020),與連線測(cè)試B耗費(fèi)時(shí)間(r=-0.346,p= 0.025)及胰島素抵抗水平呈負(fù)相關(guān)(r=-0.404, p=0.024)。結(jié)論:本研究發(fā)現(xiàn),DMN在T2DM患者中呈現(xiàn)出前后部分不一致的改變,這與前期衰老及癡呆相關(guān)研究的結(jié)果較為一致。這種腦部神經(jīng)功能連接強(qiáng)度的改變可能為T(mén)2DM相關(guān)認(rèn)知功能損傷的發(fā)生機(jī)制提供一定客觀依據(jù)。第三部分:2型糖尿病患者全腦功能連接模式的異常改變目的:在第一部分的結(jié)果中,我們發(fā)現(xiàn)2型糖尿病(type 2 diabetes, T2DM)患者在某些特定腦區(qū)的自發(fā)性神經(jīng)元活動(dòng)發(fā)生異常改變,但腦區(qū)之間的相互連接是否受到疾病的影響尚未明確。本研究的主要目的是利用靜息態(tài)功能磁共振成像技術(shù),研究2型糖尿病對(duì)全腦功能連接網(wǎng)絡(luò)結(jié)構(gòu)的影響。方法:本研究包括40例T2DM患者和43例健康志愿者,所有被試行3T磁共振成像進(jìn)行功能數(shù)據(jù)采集。對(duì)全腦每個(gè)體素的功能連接強(qiáng)度進(jìn)行計(jì)算,得到功能連接強(qiáng)度(functional connectivity strength, FCS)指標(biāo),并行雙樣本t檢驗(yàn)進(jìn)行兩組間比較。其次,將比較所得的差異腦區(qū)設(shè)置為種子點(diǎn),再次進(jìn)行功能連接計(jì)算及組建比較,即從網(wǎng)絡(luò)層面研究功能連接的改變。最后,利用基于體素水平的相關(guān)分析,研究這些差異腦區(qū)功能連接變化與認(rèn)知功能評(píng)分的關(guān)系。結(jié)果:T2DM患者在左側(cè)舌回的功能連接下降,而在右側(cè)島葉及背側(cè)前扣帶回的功能連接升高(校正后P0.05)。進(jìn)一步基于種子點(diǎn)的功能連接分析發(fā)現(xiàn),左側(cè)舌回與枕葉廣泛腦區(qū)的功能連接均下降,而以島葉及扣帶回為種子點(diǎn)的網(wǎng)絡(luò)功能連接(主要為凸顯網(wǎng)絡(luò))則顯著升高)(校正后P0.05)。相關(guān)分析發(fā)現(xiàn),病人組在后扣帶回的腦血流量在校正前后均與胰島素抵抗水平呈負(fù)相關(guān),且與畫(huà)鐘測(cè)試評(píng)分呈正相關(guān)。另一方面,枕葉的血流量在校正前后均與視覺(jué)記憶相關(guān)評(píng)分呈正相關(guān)。結(jié)論:T2DM患者全腦功能連接發(fā)生異常改變,這說(shuō)明T2DM對(duì)于腦部的影響不僅僅局限于某個(gè)特定腦區(qū),而是影響了整個(gè)大腦功能連接網(wǎng)絡(luò)的結(jié)構(gòu)模式。第四部分:2型糖尿病患者腦血流量異常及其與胰島素抵抗的關(guān)系目的:腦血流灌注與認(rèn)知功能密切相關(guān),且能夠更加直觀、定量反映腦部生神經(jīng)元活動(dòng)的情況。本研究擬利用全腦磁共振動(dòng)脈自選標(biāo)記技術(shù),探討2型糖尿病患者腦血流灌注的改變及其與認(rèn)知功能損傷的關(guān)系。方法:本研究包括40例T2DM患者和41例健康志愿者。所有被試簽署知情同意書(shū),并接受認(rèn)知功能評(píng)估。磁共振掃描包括全腦磁共振動(dòng)脈自選標(biāo)記序列成像和3D高分辨率T1加權(quán)成像。為了去除腦皮質(zhì)萎縮對(duì)灌注的潛在影響,我們引入了部分體積效應(yīng)校正算法,同時(shí)計(jì)算校正前和校正后的腦血流灌注值,行雙樣本t檢驗(yàn)兩組間比較,并在全腦范圍內(nèi)尋找與認(rèn)知行為評(píng)分和糖尿病指標(biāo)密切相關(guān)的腦灌注區(qū)。結(jié)果:與對(duì)照組相比,T2DM患者的腦血流量在后扣帶回、楔前葉及雙側(cè)枕葉皮層明顯降低(校正后P值0.05)。進(jìn)行部分體積校正后,這些結(jié)果未發(fā)生明顯改變。相關(guān)分析發(fā)現(xiàn),患者后扣帶回的腦血流量在校正前后均與胰島素抵抗水平呈負(fù)相關(guān),且與畫(huà)鐘測(cè)試評(píng)分呈正相關(guān)。另一方面,枕葉的血流量在校正前后均與視覺(jué)記憶相關(guān)評(píng)分呈正相關(guān)。結(jié)論:T2DM患者在認(rèn)知功能障礙的早期即出現(xiàn)腦血流灌注減低,且減低的形式較癡呆早期相似。更為重要的是,胰島素抵抗水平增高與這些區(qū)域的血流灌注下降相關(guān),預(yù)示著胰島素抵抗可能是T2DM認(rèn)知障礙發(fā)生的重要危險(xiǎn)因素和治療靶點(diǎn)。
[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.
【學(xué)位授予單位】：東南大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R445.2;R587.2;R747.9

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