【作者】 陈海峰；

【导师】 柏峰；

【作者基本信息】 东南大学 ， 临床医学（专业学位）， 2017， 硕士

【摘要】 背景阿尔茨海默病(Alzheimer’s disease,AD)是一种起病隐匿的渐进性发展的神经功能退行性疾病,是老年期痴呆的最常见类型;轻度认知功能障碍(mild cognitive impairment,MCI)是正常老化与老年期痴呆的过渡阶段,同时已被证实为AD的高危人群。AD受遗传与环境因素影响,研究发现血管性危险因素(vascular risk factor,VRF)与认知功能减退以及AD的发病机制相关,认为VRF促进AD的发生发展。静息态功能磁共振成像(resting-stating functional magnetic resonance imaging,rs-fMRI)以其独特优势在AD相关研究中应用广泛;默认网络(default mode network,DMN)作为静息态网络的核心组成部分,在AD相关疾病的早期诊断、监测病程、观察疗效中具有不可替代的作用。目前关于VRF对MCI患者DMN影响的研究较少。因此,探索VRF对MCI患者神经网络机制的影响可为早期诊断、及时干预、延缓AD的进展提供新的思路。目的本文利用rs-fMRI基于种子点相关性分析方法探索探讨VRF对MCI患者DMN的影响。方法使用3.0T磁共振采集MCI 67例以及认知正常组(healthy control,HC)61例影像学数据。根据常见VRF(高血压、高血脂、糖尿病、吸烟、饮酒),按参与者携带危险因素个数进行分组,包括NVRF组(无血管危险因素)、VRF1组(一个血管危险因素)、VRF>1组(两个及以上血管危险因素),即MCI亚组(NVRF 组 24 例,VRF1 组 21 例,VRF>1 组 22 组),HC 亚组(NVRF 组16 例,VRF1 组 20 例,VRF>1 组 25 例)。以后扣带回(posterior cingulate cortex,PCC)为种子点进行功能连接分析,构建各个亚组DMN以及通过双因素方差分析方法探讨疾病主效应、VRF主效应以及交互效应脑区网络。进一步分析交互效应脑区功能连接与多维度认知评分的相关性。结果疾病主效应提示:MCI组较HC组双侧颞中回、双侧中扣带回、右侧海马旁回功能连接增强;血管危险因素主效应提示:伴有血管危险因素组较无血管危险组左侧楔前叶以及右侧额上回功能连接增强;疾病与血管危险因素的交互效应主要作用于双侧额中回。其中左侧额中回功能连接与执行功能评分相关分析示:HC-VRF>1组呈负相关(r=-0.512,p=0.018),MCI-NVRF组呈负相关(r=-0.539,p=0.014),MCI-VRF1 组呈正相关(r=0.537,p=0.026),MCI-VRF>1组呈负相关(r=-0.482,p=0.043)。结论异常的背外侧前额叶皮质功能连接可能是VRF影响AD病程的重要影像学标记物。MCI的代偿能力存在VRF剂量依赖效应:伴有一个危险因素时其脑功能代偿能力受到抑制,而在无危险因素及多个危险因素状态下代偿机制被激活,其中病理生理学机制有待进一步研究。更多还原

【Abstract】 BackgroundAlzheimer’s disease(AD)is a progressive,degenerative disease with an insidious onset,and AD is the most common type of dementia in the elderly.Mild cognitive impairment(MCI)is considered as a transitional stage of normal aging and senile dementia,and has been confirmed as a high risk group of AD.The cause is not known,but it is thought to be the result of a combination of genetic and environmental factors.The studies have found that vascular risk factors(VRFs)were associated with cognitive decline and AD pathogenesis,promoting the occurrence and development of AD.Resting-state functional magnetic resonance imaging(rs-fMRI),with its unique advantages,have wide application in AD research.The default mode network(DMN)as a core part of the resting-state networks,plays an irreplaceable role in early diagnosis,monitoring,therapeutic observation in AD-related diseases.Little is known about the potential impacts of VRFs on the DMN and their underlying neural substrates in MCI patients.Therefore,to explore how VRF influence the neural network mechanism of MCI patients,can provide a new idea for early diagnosis,timely intervention and delay the progress of AD.ObjectivesTo explore the potential effect of VRF on DMN in MCI patients by rs-fMRI based on the seed point.Methods128 elderly Han Chinese participants(67 MCI subjects and 61 matched normal elderly or healthy control(HC))with or without VRFs(hypertension,diabetes mellitus,hypercholesterolemia,smoking and alcohol drinking)underwent the rs-fMRI and neuropsychological tests.According to the VRF burden,the subgroups were as follows:MCI(NVRF= 24,VRF1=21,VRF>1=22),HC(NVRF=16,VRF1=20,VRF>1=25).We obtained the default mode network(DMN)to identify alterations in MCI with the varying number of the VRF and analysed the significant correlation with behavioral performance.ResultsRegions related to the main effect of disease were observed in right parahippocampal gyrus and bilateral middle temporal gyrus and middle cingulate gyrus,while the main effect of VRF was detected in right superior frontal gyrus and left precuneus.Additionally,effects of diseasexVRF interaction was primarily in bilateral dorsolateral prefrontal cortex(DLPFC)(i.e.,middle frontal gyrus).We found an intriguing pattern about the relation between executive function(subdomain:Similarity)and altered function connectivity of posterior cingulate cortex(PCC)within the left DLPFC.Firstly,in HC-VRF>1 subgroup,the left DLPFC was significantly negatively correlated with performance on the Similarity(r=-0.512,p=0.018).And then,the left DLPFC displayed significantly negative relation to the performance of the Similarity(r=-0.539,p= 0.014)in MCI-NVRF subgroup.When MCI with VRF1,the alteration of PCC with the left DLPFC was positively correlated with the changes in Similarity scores(r= 0,537,p= 0.026).Furthermore,significantly negative correlation between Similarity scores and increased functional connectivity was found in MCI subgroup with VRF>1(r=-0.482,p= 0.043).ConclusionThese findings suggested that the dose-dependent effects of VRF on DLPFC were highlighted in MCI,and the dynamic compensatory neural processes fluctuated with variation of VRF loading may be a key role in the progression of MCI.更多还原