Using voxel-based morphometry to map the structural changes associated with rapid conversion in MCI: a longitudinal MRI study

Capturing the dynamics of gray matter (GM) atrophy in relation to the conversion from mild cognitive impairment (MCI) to clinically probable Alzheimer's disease (AD) would be of considerable interest. In this prospective study we have used a novel longitudinal voxel-based method to map the progression of GM loss in MCI patients over time and compared converters to non-converters. Eighteen amnestic MCI patients were followed-up for a predefined fixed period of 18 months and conversion was judged according to NINCDS-ADRDA criteria for probable AD. Each patient underwent a high-resolution T1-weighted volume MRI scan both at entry in the study and 18 months later. We used an optimal VBM protocol to compare baseline imaging data of converters to those of non-converters. Moreover, to map GM loss from baseline to follow-up assessment, we used a modified voxel-based morphometry (VBM) procedure specially designed for longitudinal studies. At the end of the follow-up period, seven patients had converted to probable AD. Areas of lower baseline GM value in converters mainly included the hippocampus, parahippocampal cortex, and lingual and fusiform gyri. Regions of significant GM loss over the 18-month follow-up period common to both converters and non-converters included the temporal neocortex, parahippocampal cortex, orbitofrontal and inferior parietal areas, and the left thalamus. However, there was significantly greater GM loss in converters relative to non-converters in the hippocampal area, inferior and middle temporal gyrus, posterior cingulate, and precuneus. This accelerated atrophy may result from both neurofibrillary tangles accumulation and parallel pathological processes such as functional alteration in the posterior cingulate. The ability to longitudinally assess GM changes in MCI offers new perspectives to better understand the pathological processes underlying AD and to monitor the effects of treatment on brain structure.     

阿尔茨海默病患者静息态下磁共振成像对小脑功能评估价值

【目的】应用静息态功能磁共振成像技术(fMRI)观察阿尔茨海默病(Alzheimer's disease,AD)患者,轻度认知功能障碍(mild cognition impairment,MCI)和正常人静息态下小脑齿状核功能连接改变的差异。【方法】对19例 AD 患者,16例 MCI 患者及19例正常对照者在静息态下行 fMRI 检查。以双侧齿状核为感兴趣区,对功能连接的相关系数进行双样本 t 检验,比较不同组别小脑功能连接改变的差异。【结果】AD 组小脑齿状核与左缘上回/顶下小叶、右豆状核、左顶下小叶、双侧前额叶功能连接低于正常对照组,而右颞下回、双侧枕下回、右小脑前叶、右颞中回、右中央前回、左中央后回功能连接高于正常对照组(P <0.05,AlphaSim校正)。【结论】静息态下 AD 及 MCI 患者小脑齿状核功能连接的改变提示小脑在 AD 及 MCI 发病过程中起重要作用。     

99Tcm-ECD SPECT局部脑血流显像乙酰唑胺试验对抑郁症的研究

目的观察乙酰唑胺负荷试验前后抑郁症患者局部脑血流(rCBF)的变化,评价其局部脑血管储备功能.方法以18例未经抗抑郁治疗的成年抑郁症患者为研究对象,18名年龄、性别匹配的正常志愿者作为对照组,进行99Tcm-双半胱乙酯(99Tcm-ECD)SPECT脑血流灌注断层显像,用半定量分析方法测定受检者的rCBF.在第一次检查后48 h,患者口服乙酰唑胺片2克,再行SPECT脑血流显像.结果抑郁症组患者双侧上、下部额叶,双侧前、后部颞叶,双侧顶叶、左侧基底节rCBF明显降低(P＜0.01);同时,左侧顶叶rCBF灌注比对侧更低(P＜0.01).服用乙酰唑胺后,原脑内低灌注区部位的rCBF均明显增高(P＜0.01),但没能恢复到正常水平(P＞0.05).结论抑郁症患者存在着不同部位和程度的rCBF灌注减低区,乙酰唑胺脑试验可使原来呈低灌注状态的rCBF明显提高.     

轻度认知障碍进展为阿尔茨海默病过程中脑灰质体积特征改变的MRI研究

目的 探讨轻度认知障碍(MCI)患者进展为阿尔茨海默病(AD)过程中,脑灰质(包括皮层和灰质核团)萎缩发生的部位及其进展趋势。方法 自ADNI数据网站下载15例2年内进展为AD的MCI患者和14名健康老年人的MR结构图像和MMSE评分结果。15例进展为AD的MCI患者基线时间(随访开始时间)为MCI组,进展为AD时作为AD组。14名健康老年人为对照组(基线时间为NC0组,2年后为NC1组)。利用SPM 8对MCI组、AD组和对照组的全脑灰质体积进行基于体素的统计学比较。结果 与NC0组比较,MCI组和AD组双侧内侧颞叶灰质体积萎缩,且AD组左侧尾状核头部、左侧丘脑前部体积萎缩;NC1组左侧海马头部、左侧中央后回灰质体积萎缩。结论 MCI进展为AD过程中,脑灰质萎缩主要发生在与记忆相关的内侧颞叶,全脑灰质萎缩存在左侧半球严重于右侧半球的发展趋势,在边缘系统内部呈现自海马向杏仁核、丘脑的蔓延趋势。     

脑白质疏松轻度认知功能障碍静息态默认网络研究

目的通过静息态功能磁共振成像(rs-fMRI)技术对脑白质疏松(LA)轻度认知障碍(MCI)患者脑默认网络进行分析。方法LA 患者31 例,临床痴呆评分(CDR) 0.5;年龄、性别和受教育程度匹配的正常对照组27 人,CDR 为0。对入组人群进行rs-fMRI 数据采集。使用SPM5 软件进行分析处理,使用fMRI 工具盒对预处理后的数据进行独立成分分析(ICA),组间差异进行双样本t 检验。结果静息状态下,对照组默认网络包括扣带回后部/楔前叶,双侧额叶内侧,双侧颞中回,双侧顶下回、角回,双侧海马。MCI组默认网络激活区域同对照组一致;同对照组相比,MCI患者扣带回前部/左侧额叶内侧、右侧海马旁回/钩回、右侧颞下回、左侧额叶深部白质/尾状核头部激活减低,左侧尾状核/扣带回前部、左侧额叶、左侧颞上回/顶下回的激活升高。结论LA患者静息状态默认网络活动异常,可能与认知障碍的发生有关。     

Voxel- and VOI-based analysis of SPECT CBF in relation to clinical and psychological heterogeneity of mild cognitive impairment

This study aimed to explore the heterogeneity of mild cognitive impairment (MCI) and detect differences in regional cerebral blood flow (rCBF) and cognitive function between progressive mild cognitive impairment (PMCI) and stable mild cognitive impairment (SMCI) in order to identify specific changes useful for early diagnosis of dementia. SPECT was performed in 82 MCI subjects and 20 controls using Tc-99m hexamethylpropyleneamine oxime. Cognitive functions were tested in five domains which included episodic memory, semantic memory, visuospatial function, attention, and general cognitive function. After the initial examination, MCI subjects were clinically followed for an average of 2 years. Twenty-eight subjects progressed to dementia and were defined as PMCI at baseline and 54 subjects remained stable and were defined as SMCI at baseline. The baseline rCBF and cognitive function of PMCI, SMCI, and controls were compared. PMCI had decreased relative rCBF in the parietal lobes and increased relative rCBF in prefrontal cortex compared to SMCI and controls at baseline. The cognitive function of PMCI was more severely impaired compared to SMCI with respect to episodic memory and visuospatial and general cognitive function. Both SPECT and neuropsychological tests had moderate discriminant function between PMCI and SMCI at baseline with the area under the receiver operating characteristic (ROC) curve at 75-77%. The combination of these two methods improved the diagnostic accuracy with the area under the ROC curve at 82-84%. Semantic memory and attention were negatively correlated with left prefrontal relative rCBF among the study population. The results show that the clinical heterogeneity of MCI is reflected in different patterns of psychological and CBF changes. Combined SPECT investigation and neuropsychological testing might predict the future development of dementia in patients with MCI.     

Automated hippocampal shape analysis predicts the onset of dementia in mild cognitive impairment

The hippocampus is involved at the onset of the neuropathological pathways leading to Alzheimer's disease (AD). Individuals with mild cognitive impairment (MCI) are at increased risk of AD. Hippocampal volume has been shown to predict which MCI subjects will convert to AD. Our aim in the present study was to produce a fully automated prognostic procedure, scalable to high throughput clinical and research applications, for the prediction of MCI conversion to AD using 3D hippocampal morphology. We used an automated analysis for the extraction and mapping of the hippocampus from structural magnetic resonance scans to extract 3D hippocampal shape morphology, and we then applied machine learning classification to predict conversion from MCI to AD. We investigated the accuracy of prediction in 103 MCI subjects (mean age 74.1 years) from the longitudinal AddNeuroMed study. Our model correctly predicted MCI conversion to dementia within a year at an accuracy of 80% (sensitivity 77%, specificity 80%), a performance which is competitive with previous predictive models dependent on manual measurements. Categorization of MCI subjects based on hippocampal morphology revealed more rapid cognitive deterioration in MMSE scores (p<0.01) and CERAD verbal memory (p<0.01) in those subjects who were predicted to develop dementia relative to those predicted to remain stable. The pattern of atrophy associated with increased risk of conversion demonstrated initial degeneration in the anterior part of the cornus ammonis 1 (CA1) hippocampal subregion. We conclude that automated shape analysis generates sensitive measurements of early neurodegeneration which predates the onset of dementia and thus provides a prognostic biomarker for conversion of MCI to AD.     

阿尔茨海默病及轻度认知障碍所致脑灰质体积及脑功能改变

目的基于体素形态学分析(VBM)及静息态功能MRI(rs-fMRI)技术观察阿尔茨海默病(AD)及轻度认知障碍(MCI)患者全脑灰质体积及功能改变。方法对AD(AD组)、MCI患者(MCI组)各30例及正常老年人30名(HC组)采集rs-fMRI和三维磁化强度预备梯度回波序列T1加权像,比较3组全脑灰质体积、脑区分数低频振幅(fALFF)和功能连接(FC)差异。结果3组间左侧颞上回、双侧颞中回及海马旁回灰质体积差异有统计学意义;左侧距状皮层、左侧尾状核、左侧中央后回、右侧颞上回、右侧顶上回、左侧中央前回、右侧楔前叶、右侧额中回及右侧中央后回fALFF值差异有统计学意义(P均<0.05)。以左侧颞上回为种子点,AD及MCI患者同侧颞下回与对侧枕下回FC增强。结论联合运用VBM及rs-fMRI技术可为早期诊断MCI及AD提供参考依据。AD及MCI可致全脑广泛fALFF减低及同侧颞叶与对侧枕叶FC增强,AD可伴有颞叶体积减小,MCI脑灰质体积无显著改变。     

多探针PET成像观察轻度认知障碍

目的观察轻度认知障碍患者(MCI)β淀粉样蛋白(Aβ)斑块、tau蛋白沉积和FDG PET特征。方法自ADNI数据库下载半年内接受Aβ-PET、tau-PET和FDG-PET成像的40例MCI患者及30名健康人(NC组),基于视觉判断其有/无皮层Aβ滞留,并据此将MCI患者分为Aβ+MCI组和Aβ-MCI组。分别对Aβ+MCI组和Aβ-MCI组与NC组进行逐像素统计分析,提取Aβ+MCI组AD特征脑区的平均图像强度值,分析FDG与Aβ斑块和tau蛋白沉积的相关性。结果相比NC组,Aβ+MCI组Aβ斑块呈全脑弥漫升高,边缘系统和新皮层tau蛋白对称性沉积增加,双侧扣带回、顶叶及楔前叶FDG代谢降低;FDG摄取与Aβ斑块无明显相关(P均>0.05),在杏仁核(r=-0.56,P<0.01)、扣带回后部(r=-0.61,P<0.01)、海马(r=-0.45,P=0.04)、海马旁回(r=-0.51,P=0.02)、楔前叶(r=-0.49,P=0.02)和颞中回(r=-0.53,P=0.01)与tau蛋白沉积呈负相关,在顶叶亦无明显相关(r=0.01,P=0.97)。Aβ-MCI组Aβ斑块和tau蛋白沉积低于NC组。结论Aβ+MCI具有阿尔茨海默病(AD)的PET特征,可视为AD前驱阶段。     

早期相11C-PIB PET显像探讨阿尔茨海默病患者脑功能网络改变

目的 探讨阿尔茨海默病（AD）和轻度认知功能障碍（MCI）患者¹¹C-匹兹堡化合物（¹¹C-pPIB）脑灌注网络改变。方法 对14例AD（AD组）、12例MCI（MCI组）和14名认知功能正常志愿者（对照组）行¹⁸F-FDG及¹¹C-PIB双示踪剂PET显像,采用平行独立成分分析法（pICA）计算¹¹C-pPIB和¹⁸F-FDG数据中高度相关的脑网络,以双样本t检验比较AD组与对照组间和MCI组与对照组间¹⁸F-FDG低代谢与¹¹C-pPIB低灌注的差异,获得组间有差异的脑区。结果 ¹¹C-pPIB获得的脑灌注网络与¹⁸F-FDG代谢网络高度相关（r=0.92）,并与默认网络（DMN）存在空间重叠。与对照组比较,AD组¹⁸F-FDG低代谢区与¹¹C-pPIB低灌注区存在空间重叠,包括颞上回、边缘叶/海马旁回、顶上小叶、后扣带回和前扣带回;MCI组¹⁸F-FDG的低代谢脑区位于右侧直回/眶额回、左侧后扣带回、右侧颞下回和右侧顶下小叶/颞上回,¹¹C-pPIB低灌注脑区为右侧顶下小叶。结论 AD患者¹¹C-pPIB低灌注脑区与¹⁸F-FDG低代谢高度相关,并与DMN存在空间重叠。¹¹C-pPIB显像可为诊断AD提供与¹⁸F-FDG显像互补的信息。