2型糖尿病与认知障碍相关性磁共振研究现状及进展

2型糖尿病(T2DM)与认知障碍相关,且使得罹患痴呆的风险增加。尽管研究表明T2DM是认知障碍的危险因素和阿尔茨海默病(AD)的潜在危险因素,但大家熟知的只有早期的受影响的神经生物学通路。随着过去几十年神经影像学的飞速发展,相关学者对T2DM如何影响脑部结构和功能改变以及可能导致AD有了深入了解。因此,基于结构磁共振成像、脑血流量、静息态功能磁共振成像来综述T2DM、认知障碍和AD的机制及其相互关联,重点是关于磁共振神经影像学如何为临床提供更为丰富的诊断信息,为T2DM干预方案的制订提供帮助。     

2型糖尿病患者认知障碍静息态脑功能连接分析

目的利用静息态脑功能磁共振成像的f ALFF值及功能连接方法分析T2DM患者脑功能改变,探讨病情严重程度和认知障碍对于T2DM患者脑功能连接改变的影响。方法本研究基于静息态f MRI的方法,对31例T2DM患者及27例健康对照者基于比率低频振幅技术进行脑功能连接分析研究。得到病例组和对照组的所有被试者的f ALFF值并进行组间比较,获取f ALFF值有差异的脑区;以这些脑区为种子点进一步进行基于全脑体素水平的功能连接分析,最后将患者的MMSE评分与异常功能连接的脑区进行相关分析。结果结果显示多个脑区功能连接异常,T2DM患者与健康对照者相比共有7个脑区的f ALFF值出现异常增加或减低;基于这些脑区进行全脑体素水平的功能连接分析,有多个脑区出现功能连接的异常增强或减弱;患者的MMSE评分与异常功能连接的脑区存在一定的相关性。结论 T2DM患者存在多个脑区f ALFF值异常及多个功能连接异常的脑区,其中部分脑区可能是其产生认知功能及视觉功能障碍的神经病理机制,同时部分脑区存在认知及运动功能异常及代偿的神经调控机制;患者临床认知障碍与多个不同脑区的功能连接强度均有不同程度的相关。     

2型糖尿病患者认知功能障碍影响因素研究进展

随着生活水平的提高、人口老龄化、生活方式的改变,2型糖尿病(T2DM)患病人数迅速增加[1].由糖尿病引起的中枢神经系统损害日益受到人们的重视,许多资料显示,T2DM患者存在认知功能障碍[2,3].目前对T2DM 引起的认知功能障碍的发病原因及发病机制尚不清楚.本文就近年来对T2DM 患者认知功能障碍影响研究进展综述如下.     

不伴认知功能障碍早期2型糖尿病脑结构改变

目的研究不伴认知功能障碍的早期2型糖尿病(T2DM)患者脑皮层厚度及不同皮下核团体积结构改变。方法本研究选取27例不伴认知功能障碍的早期2型糖尿病患者及与之年龄、性别、受教育程度匹配的21例正常对照组,通过3.0T MR扫描仪获取3D-T₁WI图像,使用Freesurfer软件对两组间结构图像进行分析处理,评估糖尿病患者大脑皮层厚度及19个不同皮下核团体积结构改变。结果皮层厚度指标T2DM组与正常对照组相比差异无统计学意义,但额顶叶部分脑区皮层厚度有减低趋势;皮下核团T2DM组与正常对照组相比左侧苍白球、丘脑体积减小,差异有统计学意义(P<0.05),余皮下核团体积差异无统计学意义。结论 本研究对早期不伴认知功能障碍T2DM患者皮层厚度及皮下核团体积的结构探索,对评估糖尿病早期其脑损害具有一定临床价值。     

多模态功能磁共振成像技术在2型糖尿病脑认知功能损害的研究进展

糖尿病脑损害是2型糖尿病中枢系统并发症之一,其损害包括脑血流灌注、神经及功能损害等,能使认知下降的风险概率增加,甚至可发展为痴呆。在过去的十几年中,随着磁共振成像技术的进步,功能磁共振成像已被当作为一个重要工具,用来研究2型糖尿病脑损伤,特别是基于血氧水平依赖功能磁共振成像技术揭示了2型糖尿病大脑神经功能及网络的改变,已逐渐被应用于诊断2型糖尿病脑损害的研究中。近来年来发现2型糖尿病患者大脑结构、神经功能网络、血流灌注及铁含量较正常健康患者发生了变化。本文就2型糖尿病相关的神经功能影像学改变的研究进展进行系统性综述,探讨2型糖尿病患者早期脑微结构、神经功能、血流灌等改变,与认知功能、糖尿病病程及血糖、糖化血红蛋白水平关联,有助于进一步阐述2型糖尿病患者认知损伤及其结构功能改变的机制,从而达到早期诊断、提前预防的目的,为2型糖尿病脑早期损害的胰岛素治疗提供建议,帮助指导并改善患者生活水平和质量。     

二甲双胍对2型糖尿病患者认知功能的影响

2型糖尿病(T2DM)与认知功能障碍之间存在一定的联系,T2DM患者发生认知功能障碍的风险明显增加。二甲双胍是双胍类口服降糖药物,是T2DM尤其是合并肥胖患者的一线药物,但其可能加重T2DM患者的认知功能障碍,也可能对T2DM患者的认知功能有保护作用,目前尚无一致意见。探讨二甲双胍对糖尿病患者认知功能的影响及作用机制在当前医学领域中占据重要的地位,而如何改善糖尿病脑病以及提高糖尿病患者的生活质量在目前研究中具有重要意义。     

2型糖尿病患者认知功能障碍及痴呆研究进展

<正>随着生活水平的提高、人口老龄化及生活方式的改变,2型糖尿病(T2DM)认知功能障碍的发病率越来越高,其中认知功能障碍最严重的程度是痴呆。迄今为止,美国10%以上的老年人患T2DM,我国糖尿病患者数已超过4 000万人,其中T2DM占90%以上。既往研究显示,糖尿病可引起中枢神经系统损害,并认为T2DM与认知功能障碍及痴呆密切相关,数据表明T2DM患者发生痴呆的风险是普通人群的1.5².5     

大脑结构及功能磁共振成像(MRI)在糖尿病患者认知功能改变中的应用

 糖尿病与认知功能障碍存在联系，并可能增加痴呆的风险。磁共振成像（magnetic resonance imaging，MRI）技术提供多种组织量化信息，包括脑结构体积、脑微出血灶、脑损伤病变、大脑灌注、脑功能连接、白质微结构完整性等。大脑结构MRI发现糖尿病患者的认知功能障碍与脑萎缩相关；大脑功能MRI发现神经元活动信息改变，并与早期认知障碍有关。检测大脑MRI的细微改变能为糖尿病患者早期认知功能障碍提供诊断依据，具有潜在的预测价值。本文对大脑MRI多种影像标记在糖尿病患者认知功能改变中的发现及应用进行综述。     

神经丝轻链蛋白与2型糖尿病认知功能障碍关系的研究进展

2型糖尿病(T2DM)代谢异常可造成中枢神经系统的损害,从而导致认知功能下降。神经丝轻链蛋白(NFL)作为神经元轴突损伤的血液标志物,与认知功能障碍发病显著相关,并受肾功能的影响,可通过炎症反应、血脑屏障的破坏、小胶质细胞和神经元的交互作用、Tau蛋白磷酸化等参与T2DM认知功能障碍的发生发展。本文将对NFL参与T2DM认知障碍发生发展的病理生理机制和NFL与T2DM肾功能的相关性进行综述,为早期诊断和治疗T2DM患者认知功能障碍提供依据。     

中老年2型糖尿病患者尿白蛋白/肌酐与认知功能障碍相关性研究

目的:观察中老年2型糖尿病(T2DM)患者尿白蛋白/肌酐比值(UACR)对认知功能的影响,探讨二者的相关性。方法:选取中老年T2DM患者136例,根据神经认知功能测定,分为正常组66例,认知功能障碍组70例。对所有对象进行问卷调查及实验室检查,比较两组之间差异,并采用单因素分析和多因素Logistic回归分析筛选中老年T2DM患者认知功能障碍相关影响因素。结果:单因素分析:认知功能障碍组患者与正常组在空腹血糖(FBG)、糖化血红蛋白(HbA1c)、UACR、文化程度、合并抑郁状态等方面比较差异有统计学意义(P<0.05)。多因素Logistic回归分析显示,T2DM患者认知功能障碍与高FBG、HbA1c和UACR、受教育年限低、高龄相关(P<0.05)。结论:T2DM患者UACR与认知功能损害关系密切,临床上通过对其检测可早期诊断及预防中老年T2DM合并认知功能损害。     

利用弥散张量成像技术观察小血管病所致非痴呆型血管性认知障碍患者白质结构损害与认知下降的关系

目的 非痴呆型血管性认知障碍(vascular cognitive impairment, no dementia, VCIND)是血管性认知障碍最常见亚型,早期诊断是改善预后的关键。神经影像为VCIND早期诊断、严重程度及疗效评价提供依据,但传统结构磁共振(magnetic resonance imaging, MRI)不能较好阐明结构改变与认知损害的关系。本项目利用弥散张量成像技术(diffusion tensor imaging, DTI)探讨VCIND患者脑白质结构改变及其和认知障碍的关系。方法 利用DTI对31名VCIND患者和22名正常对照者进行全脑246个脑区的白质连接完整性检测,并对所有受试者进行认知评估。然后分析患者各脑区DTI各向异性程度值(fractional anisotropy, FA)和平均弥散率(mean diffusivity, MD),并与认知评分进行相关性分析及中介分析。结果 VCIND患者全脑246个脑区中的部分关键区域发生了显著的白质连接改变,尤其额叶脑区显著。FA值与总体认知评估及记忆、执行功能评分正相关,MD值与总体认知评估及记忆、执行功能评分负相关。中介分析发现VCIND患者白质结构连接的改变介导了神经心理量表评分的改变。结论 本研究显示DTI可以为VCIND的早期诊断及认知严重程度的评估提供客观影像学指标。     

Changes in functional connectivity of ventral anterior cingulate cortex in heroin abusers

Background Previous studies with animal experiments, autopsy, structural magnetic resonance imaging （MRI） and task-related functional MRI （fMRI） have confirmed that brain functional connectivity in addicts has become impaired. The goal of this study was to investigate the alteration of resting-state functional connectivity of the ventral anterior cingulate cortex （vACC） in the heroin abusers＇ brain. Methods Fifteen heroin abusers and fifteen matched healthy volunteers were studied using vACC as the region-of interest （ROI） seed. A 3.0 T scanner with a standard head coil was the imagining apparatus. T2＊-weighted gradient-echo planar imaging （GRE-EPI） was the scanning protocol. A ROI seed based correlation analysis used a SPM5 software package as the tool for all images processing. Results This study showed a functional connection to the insula vACC in heroin abusers. Compared with controls, heroin users showed decreased functional connectivity between the nucleus accumbens （NAc） and vACC, between the parahippocampala gyrus/amgdala （PHC/amygdala） and vACC, between the thalamus and vACC, and between the posterior cingulated cortex/precuneus （PCC/pC） and vACC. Conclusion The altered resting-state functional connectivity to the vACC suggests the neural circuitry on which the addictive drug has an affect and reflects the dysfunction of the addictive brain.     

Abnormal Alterations of Cortical Thickness in 16 Patients with Type 2 Diabetes Mellitus: A Pilot MRI Study

Objective The aim of this study is to investigate the cerebral cortical thickness changes in type 2 diabetes mellitus (T2DM) using a whole brain cortical thickness mapping system based on brain magnetic resonance imaging (MRI). Methods High resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MR images were obtained from 16 patients with T2DM, as well as from 16 normal controls. The whole brain cortical thickness maps were generated, and the cortical thickness of each brain region was calculated according to gyral based regions of interest (ROI) using an automated labeling system by the Freesurfer software. We compared mean cortical thickness at each brain region by the analysis of covariance with age and sex as covariates. The regional difference of the cortical thickness over the whole brain was compared by the analysis of surface-based cortical thickness. Results Mean cortical thicknesses analysis showed bilateral cerebrum in the patients with T2DM (left: 2.52±0.07 mm; right: 2.51±0.08 mm) were significant thinner than those in the normal controls (left: 2.56±0.09 mm; right: 2.56±0.09 mm) (bothP<0.05). Regional cortical thinning in T2DM was demonstrated in the paracentral lobule, postcentral gyrus, lateral occipital gyrus, lingual gyrus, precuneus, superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus and posterior cingulate gyrus, compared to the normal controls. The cortical thickness of left middle cingulate and right inferior temporal gyrus were negatively correlated with the disease course. Conclusion A widespread cortical thinning was revealed in patients with T2DM by the analysis of brain cortical thickness on MR. Our finding supports the idea that T2DM could lead to subtle diabetic brain structural changes.     

2型糖尿病脑病的多模态MRI成像

随着老龄化进程的加速,糖尿病（diabetes mellitus,DM）已成为继心脑血管疾病、恶性肿瘤之后,影响人类健康的第三大类慢性疾病。近年来,越来越多的研究发现2型糖尿病（type 2 diabetes mellitus,T2DM）可导致中枢神经系统改变,即糖尿病脑病（diabetic encephalopathy,DE）。T2DM患者进展为DE是一个隐匿性的慢性过程,早期临床症状常不典型,脑微结构、代谢、血流灌注及神经活动改变常常出现于脑部结构损害的早期阶段,甚至早于临床症状。基于多模态MRI技术,我们可以在体、定量评估T2DM的器质性脑损害,为临床评估疾病的发生、发展提供重要的影像学依据。     

Abnormal Alterations of Cortical Thickness in 16 Patients with Type 2 Diabetes Mellitus: A Pilot MRI Study△

Objective The aim of this study is to investigate the cerebral cortical thickness changes in type 2 diabetes mellitus (T2DM) using a whole brain cortical thickness mapping system based on brain magnetic resonance imaging (MRI).Methods High resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MR images were obtained from 16 patients with T2DM, as well as from 16 normal controls. The whole brain cortical thickness maps were generated, and the cortical thickness of each brain region was calculated according to gyral based regions of interest (ROI) using an automated labeling system by the Freesurfer software. We compared mean cortical thickness at each brain region by the analysis of covariance with age and sex as covariates. The regional difference of the cortical thickness over the whole brain was compared by the analysis of surface-based cortical thickness.Results Mean cortical thicknesses analysis showed bilateral cerebrum in the patients with T2DM (left: 2.52±0.07 mm; right: 2.51±0.08 mm) were significant thinner than those in the normal controls (left: 2.56±0.09 mm; right: 2.56±0.09 mm) (both P<0.05). Regional cortical thinning in T2DM was demonstrated in the paracentral lobule, postcentral gyrus, lateral occipital gyrus, lingual gyrus, precuneus, superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus and posterior cingulate gyrus, compared to the normal controls. The cortical thickness of left middle cingulate and right inferior temporal gyrus were negatively correlated with the disease course.Conclusion A widespread cortical thinning was revealed in patients with T2DM by the analysis of brain cortical thickness on MR. Our finding supports the idea that T2DM could lead to subtle diabetic brain structural changes.     

镜像同伦功能连接在轻度认知障碍脑功能检查中的应用

目的：利用静息态功能磁共振成像（rs-fMRI）基于体素的镜像同伦连接（VMHC）及基于种子的功能连接（FC）的方法探讨轻度认知障碍（MCI）患者脑网络异常改变。方法：收集MCI患者29 例纳入MCI组，收集性别、年龄和文化程度匹配的健康对照者29 例纳入HC组。两组受试对象均接受相关精神量表分析及3.0T磁共振扫描。利用VMHC方法分析两组受试对象全脑镜像同伦连接差异，采用独立样本t 检验比较两组VMHC值差异，然后以VMHC差异脑区作为种子分析其与全脑功能连接差异。结果：MCI组双侧颞上回VMHC值较HC组增加（差异体素41个，t =4.264，P ＜0.05），MCI组左侧颞上回与右侧梭状回、左侧额中回、右侧额中回的功能连接较HC组增强（P ＜0.05），右侧颞上回与左侧梭状回、左侧颞中回、右侧额下回、左侧楔叶、左侧枕中回的功能连接增强（P ＜0.05）。结论：MCI患者静息状态下双侧颞上回镜像同伦功能连接增强，提示MCI可能存在感觉语言中枢损害并伴有对侧中枢代偿性功能增强。     

Memory Dysfunction in Type 2 Diabetes Mellitus Correlates with Reduced Hippocampal CA1 and Subiculum Volumes

Background:

Little attention has been paid to the role of subcortical deep gray matter (SDGM) structures in type 2 diabetes mellitus (T2DM)-induced cognitive impairment, especially hippocampal subfields. Our aims were to assess the in vivo volumes of SDGM structures and hippocampal subfields using magnetic resonance imaging (MRI) and to test their associations with cognitive performance in T2DM.

Methods:

A total of 80 T2DM patients and 80 neurologically unimpaired healthy controls matched by age, sex and education level was enrolled in this study. We assessed the volumes of the SDGM structures and seven hippocampal subfields on MRI using a novel technique that enabled automated volumetry. We used Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA) scores as measures of cognitive performance. The association of glycosylated hemoglobin (HbA1c) with SDGM structures and neuropsychological tests and correlations between hippocampal subfields and neuropsychological tests were assessed by partial correlation analysis in T2DM.

Results:

Bilaterally, the hippocampal volumes were smaller in T2DM patients, mainly in the CA1 and subiculum subfields. Partial correlation analysis showed that the MoCA scores, particularly those regarding delayed memory, were significantly positively correlated with reduced hippocampal CA1 and subiculum volumes in T2DM patients. Additionally, higher HbA1c levels were significantly associated with poor memory performance and hippocampal atrophy among T2DM patients.

Conclusions:

These data indicate that the hippocampus might be the main affected region among the SDGM structures in T2DM. These structural changes in the hippocampal CA1 and subiculum areas might be at the core of underlying neurobiological mechanisms of hippocampal dysfunction, suggesting that degeneration in these regions could be responsible for memory impairments in T2DM patients.     

早发性精神分裂症脑功能连接的功能磁共振

目的：探讨早发性精神分裂症患者在静息状态下是否存在脑功能连接异常以及异常区域的定位。方法：采用第4版美国精神障碍诊断与统计手册（diagnostic and statistical manual, fourth edition,DSM-IV）诊断标准诊断早发性精神分裂症患者19例。对19例早发性精神分裂症患者及19例正常对照分别进行静息状态下的功能磁共振(fMRI)检查。选取扣带回为感兴趣区,对早发性精神分裂症患者和正常对照进行静息状态下全脑的磁共振脑功能扫描。比较两组的脑区与扣带回之间的功能连接的差异,对处理后的两组功能连接的图像,以体素为基础,进行两样本t检验。 结果：早发性精神分裂症在静息状态下存在功能连接的异常,包括功能连接减低和功能连接增强。功能连接减低的脑区包括双侧小脑后叶、额上回、额中回、直回、海马、楔回、梭状回、枕中回、枕下回、右侧颞下回、右侧颞中回、右侧角回。而功能连接增强的区域为左侧颞中回和左侧颞下回。 结论：早发性精神分裂症在静息状态下存在脑区与扣带回的功能连接异常。静息状态下的fMRI将在精神分裂症的研究中发挥重要作用。