本文選題：血管危險因素 + 弗明漢卒中風險　； 參考：《武漢大學》2014年博士論文

【摘要】：第一部分弗明漢卒中風險與認知損害 目的：高血壓、糖尿病等血管危險因素可以不依賴卒中事件及明顯的腦結(jié)構(gòu)性損害而增加認知損害的風險,但是多種共存的血管危險因素對認知功能的累積效應(yīng)尚不明確。本研究探討了弗明漢血管危險因素與認知損害之間的關(guān)系及其認知域損害特點。 方法：這是一項基于社區(qū)人群的橫斷面研究。共有184名年齡在50—80歲的非卒中自愿者納入研究,按照弗明漢10年卒中風險評估方法,將受試者分為低危組(10年卒中風險10%),中危組(10年卒中風險為10%--20%)及高危組(10年卒中風險20%)。使用一系列的認知量表測試受試者的認知功能,其中包括全腦認知功能、執(zhí)行功能、注意力、延遲回憶及瞬時回憶能力。為了控制可能的混雜因素,所有受試者均完成了頭顱磁共振掃描,計算了腦白質(zhì)高信號體積及腔隙性腦梗死個數(shù),并在回歸模型中調(diào)整了這兩個可能損害認知功能的混雜因素。采用線性回歸方法分析了弗明漢卒中風險與各個認知域之間的相關(guān)性。為了探索弗明漢血管危險因素中各個變量對認知功能的歸因權(quán)重,進一步行貝葉斯逐步判別分析法。 結(jié)果：隨著弗明漢10年卒中風險增加,受試者的總體認知功能、執(zhí)行能力、記憶能力均有不同程度的損害。與低危組相比,高危組的Moca評分(P0.001)、數(shù)字符號轉(zhuǎn)換測試(P0.001)、倒背(P=0.044)、延遲回憶評分(P0.001)及言語流暢性測試(P=0.041)均顯著下降。與低危組相比,中危組的數(shù)字符號轉(zhuǎn)換測試(P=0.034)和延遲回憶(P=0.014)顯著下降。在調(diào)整腦白質(zhì)高信號體積及腔梗后,弗明漢10年卒中風險仍與總體認知功能(r=-0.451,P=0.001)、延遲回憶(r=-0.352,P=0.010)和執(zhí)行功能(r=-0.311,P=0.025)之間存在顯著的線性相關(guān)性。貝葉斯逐步判別分析顯示收縮壓、年齡、糖尿病史及吸煙史是對認知功能狀態(tài)影響重要的四個因素,其中風險越高,對于這些因素的要求也是相對越高。 結(jié)論：基于結(jié)構(gòu)磁共振觀察,血管危險因素可以不依賴血管性腦損害途徑而導致認知損害,其中延遲回憶和執(zhí)行能力是兩個主要受累的認知域。 第二部分腦內(nèi)生化代謝異常介導了血管危險因素相關(guān)的認知損害 目的：在第一部分研究中,我們已經(jīng)證實血管危險因素可以獨立于卒中及明顯的結(jié)構(gòu)性腦損害而增加認知損害的風險,但是其病理生理基礎(chǔ)尚未闡明。本部分研究目的是探討腦內(nèi)生化代謝改變是否介導了與血管危險因素相關(guān)的認知功能損害。 方法：這是一項橫斷面病例對照研究,總共納入了54例具有不同程度血管危險因素的受試者。使用弗明漢10年卒中風險評分來量化血管危險因素負擔。所有受試者均完成了包括全腦認知功能、學習記憶功能和執(zhí)行功能在內(nèi)的完整的神經(jīng)心理評估。所有受試者均接受了3.0T單體素磁共振波譜掃描(PRESS序列),感興趣容積為左側(cè)前額葉皮層、左側(cè)海馬。使用LC-Model分析波譜數(shù)據(jù),計算出N乙酰天冬氨酸(NAA)、膽堿復合物(Cho)、肌醇(Ins)、谷氨酸復合物(Glx)和肌酸(Cr)濃度。按照弗明漢10年卒中風險大小,將受試者分為低危組(10%)、中危組(10—20%)和高危組(20%)。本研究注冊號ChiCTR-RNC-12002205。 結(jié)果：與低危組相比,高危組受試者的工作記憶能力(3.9±1.0vs4.8±1.1,P0.05)、延遲回憶能力(7.1±1.5vs9.1±1.5,P0.01)和執(zhí)行功能(27.8±6.2vs37.1±6.5,P0.01)顯著損害。高危組受試者左側(cè)海馬Glx/Cr值(1.21±0.25versus1.48±0.22,P0.01)和左側(cè)額葉NAA/Cr值(1.33±0.14versus1.66±0.33,P0.01)明顯低于低危組。就總體樣本而言,在調(diào)整了腔隙性腦梗死計數(shù)及腦白質(zhì)高信號體積后,FSRP評分與左側(cè)海馬Glx/Cr(r=-0.332,P=0.016)及左側(cè)額葉NAA/Cr(r=-0.287,P=0.039)也呈顯著的負性線性相關(guān)。左側(cè)額葉皮層NAA/Cr值與數(shù)字符號測試(執(zhí)行功能)之間呈顯著的正性相關(guān)(r=0.327,P=0.016),左側(cè)海馬Glx/Cr值與延遲回憶測試呈顯著的正向相關(guān)(r=0.419,P=0.002)。當逐步納入左側(cè)海馬Glx/Cr值和左側(cè)額葉NAA/Cr值后,FSRP與認知功能評估之間的相關(guān)性系數(shù)明顯降低,提示上述神經(jīng)生化代謝改變介導了弗明漢卒中風險與認知功能之間的關(guān)系。 結(jié)論：延遲回憶及執(zhí)行功能損害仍是血管危險因素相關(guān)性認知功能損害的兩個主要的認知域損害。腦內(nèi)生化物質(zhì)代謝及谷氨酸遞質(zhì)水平的改變可能介導了血管危險因素相關(guān)的認知功能損害。 第三部分血腦屏障通透性異常介導了血管危險因素相關(guān)的認知損害 目的：血腦屏障功能損害在血管性癡呆及阿爾茨海默爾病中均起到了重要作用,但是在更為早期的血管危險因素相關(guān)性認知損害中的作用尚不明確。本部分研究目的是探討左側(cè)海馬和左側(cè)額葉皮層下白質(zhì)血腦屏障通透性指數(shù)改變是否介導了血管危險因素相關(guān)的認知功能損害。 方法：這是一項橫斷面小樣本的初步研究,本部分研究的納入對象來源于第一部分中的低危組和高危組,總共納入了22例具有不同程度血管危險因素的受試者,我們使用弗明漢卒中風險評分來量化血管危險因素負擔,按照弗明漢10年卒中風險大小,將受試者分為低危組(10%)和高危組(20%)。所有受試者均完成了包括全腦認知功能、學習記憶功能和執(zhí)行功能在內(nèi)的完整的神經(jīng)心理評估。所有受試者均接受了3.0T動態(tài)對比增強磁共振(快速T1映像TAPIR序列),感興趣區(qū)域為左側(cè)額葉皮層下白質(zhì)和左側(cè)海馬。使用CINE圖像分析軟件,基于改良的Tofts模型計算感興趣區(qū)域血腦屏障通透性指數(shù)和血管容積指數(shù)。時間信號曲線對應(yīng)的峰值(30秒時的感興趣區(qū)域信號強度)定義為血管容積指數(shù),反映了由對比劑填充的局部組織血管容積大小,定義180秒時的信號強度與峰值的比值為血腦屏障通透性指數(shù)。本研究注冊號ChiCTR-RNC-12002205。 結(jié)果：與低危組相比,高危組患者的年齡更大(74.3±3.7vs56.7±6.9,P0.01),收縮壓更高(143.5±16.0vs129.0±13.0,P0.05),腦白質(zhì)高信號更明顯(1.5±2.2vs7.1±3.8,P0.01)。所有患者在注射對比劑后30秒時的信號強化達到高峰,此后隨著時間的推移,信號強度逐漸減弱。在左側(cè)海馬水平,高危組的強化信號峰值(0.238±0.17)顯著高于低危組(0.264±0.16),而兩組受試者左側(cè)額葉皮層下白質(zhì)的血管容積指數(shù)無顯著差異。在左側(cè)海馬水平,低危組受試者時間-信號曲線下降斜率顯著高于高危組,提示對比劑在高危組滯留的量和時間要多于低危組,反映了高危組受試者左側(cè)海馬的血腦屏障通透性指數(shù)顯著高于低危組,而在左側(cè)額葉皮層下白質(zhì)水平,兩組受試者的通透性指數(shù)無顯著差異。Pearson相關(guān)性分析結(jié)果顯示,在調(diào)整腦白質(zhì)病變體積和腔梗的情況下,FSRP與左側(cè)海馬血腦屏障通透性指數(shù)呈顯著的線性正相關(guān)(r=-0.576,P=0.006)。左側(cè)海馬血腦屏障通透性指數(shù)與延遲回憶測試之間呈顯著的負性相關(guān)(r=0.596,P=0.002)。 結(jié)論：血腦屏障通透性改變可能是血管危險因素導致腦損傷的一種形式,并且可能介導了早期的危險因素相關(guān)性認知損害。
[Abstract]:The first part of fiminghan stroke risk and cognitive impairment
Objective: vascular risk factors such as hypertension and diabetes can increase the risk of cognitive impairment without dependence on stroke events and obvious brain structural damage, but the cumulative effect of various coexisting vascular risk factors on cognitive function is not clear. The characteristics of its cognitive domain damage.
Methods: This is a cross-sectional study based on community population. A total of 184 non stroke volunteers aged 50 to 80 years of age were enrolled in the study. The subjects were divided into low risk group (10 year stroke risk 10%), middle risk group (10 year apoplexy 10%--20%) and high-risk group (10 year stroke risk 20%). A series of cognitive scales were used to test the cognitive function of the subjects, including the whole brain cognitive function, executive function, attention, delayed recall, and instantaneous memory. In order to control possible confounding factors, all subjects completed the skull magnetic resonance scan, calculated the high signal volume of white matter and the number of lacunar cerebral infarction, and were regressive. This model adjusts the two confounding factors that may damage cognitive function. The linear regression method is used to analyze the correlation between the risk of fingham stroke and the different cognitive domains. In order to explore the attribution weight of each variable to cognitive function in the viminghan vascular risk factors, the Bayesian stepwise discriminant analysis is further carried out.
Results: with the increased risk of stroke in fingham 10 years, the subjects' overall cognitive function, executive ability and memory ability were impaired in varying degrees. Compared with the low risk group, the Moca score (P0.001), the digital symbol conversion test (P0.001), the reverse (P=0.044), the delayed recall score (P0.001) and the verbal fluency test (P=0.041) were all significant compared with the low risk group. Decline. Compared with the low risk group, the digital symbol conversion test (P=0.034) and the delayed memory (P=0.014) decreased significantly in the middle risk group. The 10 year stroke risk in fingham was still associated with the overall cognitive function (r=-0.451, P=0.001), delayed memory (r=-0.352, P=0.010) and executive function (r=-0.311, P=0.025) after adjusting the high signal volume and infarction of the brain white matter. A significant linear correlation. Bayes stepwise discriminant analysis showed that systolic pressure, age, diabetes history and smoking history were four important factors affecting cognitive function, and the higher the risk, the higher the requirements for these factors.
Conclusion: Based on structural MRI observation, vascular risk factors can lead to cognitive impairment without dependent on the vascular brain damage pathway, in which delayed recall and execution are two major cognitive domains.
The second part of brain metabolic abnormalities mediate cognitive impairment associated with vascular risk factors.
Objective: in the first part of the study, we have confirmed that vascular risk factors can increase the risk of cognitive impairment independently of stroke and obvious structural brain damage, but its pathophysiological basis has not been elucidated. The purpose of this study is to explore whether changes in biochemical metabolism in the brain mediate the knowledge related to vascular risk factors. Functional damage.
Methods: This is a cross-sectional case control study. A total of 54 subjects with a different degree of vascular risk were included. The 10 year stroke risk score was used to quantify the burden of vascular risk factors. All subjects completed a complete nerve including whole brain cognitive function, memorizing function, and performing function. Psychological assessment. All subjects received 3.0T monosin magnetic resonance spectroscopy (PRESS sequence). The interest volume was the left prefrontal cortex and the left hippocampus. Using LC-Model analysis, the N acetylaspartic acid (NAA), the choline complex (Cho), the muscle alcohol (Ins), the glutamic acid complex (Glx) and the creatine (Cr) concentration were calculated. 10 year risk of stroke, the subjects were divided into low risk group (10%), middle risk group (10 - 20%) and high-risk group (20%). Registration number ChiCTR-RNC-12002205.
Results: compared with the low risk group, the working memory ability of the subjects at high risk group (3.9 + 1.0vs4.8 + 1.1, P0.05), delayed recollection (7.1 + 1.5vs9.1 + 1.5, P0.01) and executive function (27.8 + 6.2vs37.1 6.5, P0.01) were significantly impaired. The left hippocampus Glx/Cr value (1.21 + 0.25versus1.48 + 0.22, P0.01) and the left frontal lobe NAA/Cr value (1.33 + 0) in the high risk group were (1.33 + 0). .14versus1.66 + 0.33, P0.01) was significantly lower than that in the low risk group. As to the overall sample, the FSRP score was also negatively correlated with the left hippocampus Glx/Cr (r=-0.332, P=0.016) and the left frontal lobe NAA/Cr (r=-0.287, P=0.039) after adjusting the lacunar cerebral infarction count and the high signal volume of the white matter. The NAA/Cr value and the digital character of the left frontal cortex There was a significant positive correlation between the number test (r=0.327, P=0.016). The left hippocampal Glx/Cr value was significantly positively correlated with the delayed memory test (r=0.419, P=0.002). The correlation coefficient between FSRP and cognitive energy assessment was significantly reduced when the left hippocampal Glx/Cr value and the left frontal lobe NAA/Cr value were gradually incorporated. Biochemical metabolic changes mediate the relationship between Framingham stroke risk and cognitive function.
Conclusion: delayed recall and executive functional impairment are still two major cognitive impairments of cognitive impairment associated with vascular risk factors. The changes in metabolism of biochemical substances and glutamate levels in the brain may mediate the impairment of cognitive function related to vascular risk factors.
The third part is the abnormal permeability of blood brain barrier, which mediates the cognitive impairment associated with vascular risk factors.
Objective: the impairment of blood brain barrier function plays an important role in both vascular dementia and Alzheimer's disease, but the role in the more early vascular risk factors related cognitive impairment is not clear. The purpose of this study is to explore the changes in the permeability index of the white matter blood brain barrier under the left hippocampus and left frontal cortex. Whether or not mediated the cognitive impairment of vascular risk factors.
Methods: This is a preliminary study of a small cross-sectional sample. This part of the study came from the low and high risk groups in the first part of the study. A total of 22 subjects with different degree of vascular risk were included. We used the famingham stroke risk score to quantify the burden of vascular risk factors, according to fingham's 10 years of death. The subjects were divided into low risk group (10%) and high risk group (20%). All subjects completed a complete neuropsychological assessment including whole brain cognitive function, learning memory function and executive function. All subjects received 3.0T dynamic contrast enhanced magnetic resonance (fast T1 image TAPIR sequence), and the region of interest was left to the left The subcortical white matter and the left hippocampus of the frontal cortex. Using the CINE image analysis software, the blood brain barrier permeability index and blood vessel volume index are calculated based on the improved Tofts model. The peak value of the time signal curve corresponding to the time signal (the intensity of the region of interest at 30 seconds) is defined as the volume index of the blood tube, reflecting the local area filled with the contrast agent. The ratio of signal intensity to peak value was defined as blood-brain barrier permeability index at 180 seconds. The registration number is ChiCTR-RNC-12002205.
Results: compared with the low risk group, the patients in the high risk group were older (74.3 + 3.7vs56.7 + 6.9, P0.01), the systolic pressure was higher (143.5 + 16.0vs129.0 + 13, P0.05), and the high signal of white matter was more obvious (1.5 + 2.2vs7.1 3.8, P0.01). The signal intensities reached the peak at 30 seconds after the injection of contrast agents. At the left hippocampal level, the peak value of the enhanced signal (0.238 + 0.17) in the high risk group was significantly higher than that in the low risk group (0.264 + 0.16), but there was no significant difference in the volume index of the blood vessel in the left frontal cortex of the two groups. The amount and time of retention in the high risk group were more than those in the low risk group. It showed that the blood brain barrier permeability index of the left hippocampus in the high risk group was significantly higher than that in the low risk group, while in the left frontal cortex, there was no significant difference in the permeability index between the two groups. The results of the.Pearson phase analysis showed that the brain white matter lesion was adjusted. There was a significant linear positive correlation between FSRP and the permeability index of the left hippocampal blood-brain barrier (r=-0.576, P=0.006). There was a significant negative correlation between the permeability index of the left hippocampal blood-brain barrier and the delayed memory test (r=0.596, P=0.002).
Conclusion: the change of blood brain barrier permeability may be a form of brain damage caused by vascular risk factors and may mediate early risk factors associated cognitive impairment.

【學位授予單位】：武漢大學
【學位級別】：博士
【學位授予年份】：2014
【分類號】：R743.3;R445.2

【參考文獻】

相關(guān)期刊論文 前2條

1 M.A.Binnewijzend;J.P.A.Kuijer;M.R.Benedictus;W.M.van der Flier;A.M.Wink;M.P.Wattjes;林江南;;應(yīng)用3D準連續(xù)性動脈自旋標記MR成像對阿爾茨海默病和輕度認知障礙病人的腦血流量測量:疾病嚴重程度的一種標志[J];國際醫(yī)學放射學雜志;2013年03期

2 舒敏;章軍建;董燕;張在鵬;;Significance of Increased CIMT with Coexisting Carotid Plaques in Cerebral White Matter Lesions in Elders[J];Journal of Huazhong University of Science and Technology(Medical Sciences);2013年01期

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