轻度认知功能障碍及阿尔茨海默病脑白质的MR扩散张量成像研究

目的 应用MR DTI方法评价轻度认知功能障碍(MCI)及阿尔茨海默病(AD)脑白质微观结构完格性,进一步探讨脑白质异常与认知功能损害之间的关系.方法 选取9例遗忘型MCI(MCI组)、15例可能AD(AD组)和11名年龄匹配的正常老年人(NC组),对常规腩部MRI脑白质表现正常的部位进行DTI扫描,测量不同脑区的各向异性指数(FA)及平均扩散率(MD),应用单因素方差分析对3组相应区域进行组间比较,并对所有被试DTI指数与临床认知评价量表积分进行相关性检验.结果 MCI患者顶叶、半卵圆中心、后扣带回、海马旁回、颞叶、额叶FA值分别为0.31±0.03、0.39±0.03、0.62±0.05、0.59±0.05、0.47±0.08、0.32±0.04,MD值分别为(899±30)×10-6、(782±53)×10-6、(732±45)×10-6、(806±38)×10-6、(772±55)×10-6、(792±35)×10-6mm2/s.AD患者相应部位FA值分别为0.28±0.04、0.37±0.03、0.55±0.06、0.52±0.05、0.40±0.05、0.27±0.04,MD值分别为(912±37)×10-6、(800±67)×10-6、(762±46)×10-6、(874±57)×10-6、(822±55)×10-6、(822±39)×10-6mm2/s.NC组FA值分别为0.36±0.03、0.43±0.05、0.64±0.05、0.60±0.05、0.52±0.05、0.33±0.03,MD值分别为(866±37)×10-6、(754±54)×10-6、(718±32)×10-6、(810±39)×10-6、(755±48)×10-6、(785±23)×10-6mm2/s.与NC组对比,MCI组的顶叶FA值明显下降(P<0.01),AD组顶叶、半卵圆中心FA值亦明显减低(P<0.01),且后扣带回、海马旁回及颞叶、额叶脑白质FA值及相应MD值差异有统计学意义(P<0.05),同时这些区域DTI指数与临床认知评价量表积分具有相关性(P<0.05).结论 MR DTI能够探测AD及MCI患者脑白质微观结构异常,顶叶脑白质FA值的异常在认知功能损害的早期即已发生,该脑区白质异常改变及区域性失联络在痴呆进程中可能起到重要作用.     

基于体素的遗忘型轻度认知障碍和轻度阿尔茨海默病全脑白质MR扩散张量成像分析

目的 采用基于体素的分析(VBA)方法研究遗忘型轻度认知障碍(aMCI)患者和轻度阿尔茨海默病(AD)患者全脑白质微观结构改变的特点及其与灰质萎缩模式的关系.方法 选取33例aMCI患者(aMCI组)、32例轻度AD患者(轻度AD组)和31名正常老年人(健康对照组),对全脑进行3.0 T DTI及三维快速扰相梯度反转回波(3DFSPGR)脉冲序列扫描.采用统计参数图(SPM)5软件对被试者的结构图像及各向异性(FA)图进行预处理,然后采用t检验对aMCI组、轻度AD组和正常对照组的全脑灰质体积及FA值进行基于体素的统计学比较,计算出有统计学意义的脑区.结果 与正常对照组比较,aMCI组的双侧额颞叶和左侧枕叶白质、左侧扣带前部、左侧顶下小叶、右侧脑室三角区外上方白质的FA值减低;轻度AD组的双侧额颞枕叶、海马旁白质、扣带前部、胼胝体、侧脑室三角区旁白质、顶下小叶、左侧颞于、左侧丘脑、右侧楔前叶FA值减低.基于体素的形态测量学(VBM),分析发现,aMCI患者组左侧海马、海马旁回、舌回、颞上回,双侧岛叶、颞中回出现了灰质萎缩;轻度AD患者组双侧海马、海马旁回、杏仁核、丘脑、额叶、颞叶、顶叶、枕叶皮质出现了灰质萎缩.aMCI与轻度AD患者组全脑白质FA值减低的模式与灰质萎缩模式不同.aMCI组与轻度AD组比较未发现具有统计学意义的FA值减低脑区.aMCI、轻度AD患者组全脑白质FA值与简易智能精神状态检查量表(MMSE)评分没有相关性.结论 基于体素的MR DTI全脑白质分析能够较全面、客观地揭示aMCI、轻度AD的脑白质损害的模式.aMCI、轻度AD患者白质损害的模式与灰质不同,提示脑白质病变是多种病理机制导致的.aMCI患者向轻度AD进展过程中,脑白质各向异性改变不显著,脑白质FA值的改变可能无法反映患者认知功能障碍的严重程度.

Abstract：

Objective To evaluate the microstructural integrity of white matter (WM) in patients with amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD) using voxel-based analysis (VBA), and investigate the relationship between WM abnormalities and gray matter(GM) atrophy.Methods Thirty-three cases with aMCI, 32 cases with mild AD and 31 normal aging volunteers as control subjects were scanned on a 3.0 T MR system using diffusion tensor imaging (DTI) and three-dimensional spoiled gradient-recalled(3DSPGR) sequences. Fractional anisotropy (FA) maps and morphological images were preprocessed by SPM5 and voxel-based comparisons between the 2 patient groups and the control group were performed by t test. Results Relative to the control group, patients with aMCI showed significantly reduced FA value in bilateral frontal, temporal and left occipital WM, left anterior part of cingulum, left inferior parietal lobule, and the W M adjacent to the triangular part of the right lateral ventricle(k≥20 voxels).In mild AD,significantly reduced FA value was found in bilateral hippocampal,inferior parietal lobular,frontal,temporal,and occipital WM,bilateral corpus callosum,anterior part of cingulums,the WM adjacent to the triaangular part of the bilateral lateral ventricles,left temporal stem,left thalamus,right precuneus(k≥20 voxels).Significantly reduced GM volume was found in left hippocampus,parahippocampal gyrus,lingual gyrus and superior temporal gyrus,bilateral insulae and middle temporal gyri in aMCl group whencompared with control group(k≥50 voxels).In mild AD,significantly reduced GM volume was found in bilateral hippoeampi,parahippocampal gyri,amygdalae,thalami,temporal,parietal,frontal,occipital cortex(k≥50 voxels).The pattern of areas with reduced FA differs;from that of the GM volumetric reduction.No areas with significantlv reduced FA was detected in aMCl compared with mild AD. There was no significant correlation between FA value of WM in patient groups and Mini-Mental State Examination(MMSE)scores.Conclusions Voxel-based MRI DTI analysis of whole brain white matter can objectively reveal widespread white matter abnormalities in early-stage AD.The difierence between WM FA reduction pattern and GM volumetric reduction pattern indicates that the pathological WM changes in earlyslage AD were caused by multiple mechanisms. FA did not vary significantly in patients pr0gressing from aMCI to mild AD and can hardly reflect the severitv of cognitive function damage in these patients.     

基于体素的遗忘型轻度认知障碍和轻度阿尔茨海默病全脑白质MR扩散张量成像分析

Objective To evaluate the microstructural integrity of white matter (WM) in patients with amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD) using voxel-based analysis (VBA), and investigate the relationship between WM abnormalities and gray matter(GM) atrophy.Methods Thirty-three cases with aMCI, 32 cases with mild AD and 31 normal aging volunteers as control subjects were scanned on a 3.0 T MR system using diffusion tensor imaging (DTI) and three-dimensional spoiled gradient-recalled(3DSPGR) sequences. Fractional anisotropy (FA) maps and morphological images were preprocessed by SPM5 and voxel-based comparisons between the 2 patient groups and the control group were performed by t test. Results Relative to the control group, patients with aMCI showed significantly reduced FA value in bilateral frontal, temporal and left occipital WM, left anterior part of cingulum, left inferior parietal lobule, and the W M adjacent to the triangular part of the right lateral ventricle(k≥20 voxels).In mild AD,significantly reduced FA value was found in bilateral hippocampal,inferior parietal lobular,frontal,temporal,and occipital WM,bilateral corpus callosum,anterior part of cingulums,the WM adjacent to the triaangular part of the bilateral lateral ventricles,left temporal stem,left thalamus,right precuneus(k≥20 voxels).Significantly reduced GM volume was found in left hippocampus,parahippocampal gyrus,lingual gyrus and superior temporal gyrus,bilateral insulae and middle temporal gyri in aMCl group whencompared with control group(k≥50 voxels).In mild AD,significantly reduced GM volume was found in bilateral hippoeampi,parahippocampal gyri,amygdalae,thalami,temporal,parietal,frontal,occipital cortex(k≥50 voxels).The pattern of areas with reduced FA differs;from that of the GM volumetric reduction.No areas with significantlv reduced FA was detected in aMCl compared with mild AD. There was no significant correlation between FA value of WM in patient groups and Mini-Mental State Examination(MMSE)scores.Conclusions Voxel-based MRI DTI analysis of whole brain white matter can objectively reveal widespread white matter abnormalities in early-stage AD.The difierence between WM FA reduction pattern and GM volumetric reduction pattern indicates that the pathological WM changes in earlyslage AD were caused by multiple mechanisms. FA did not vary significantly in patients pr0gressing from aMCI to mild AD and can hardly reflect the severitv of cognitive function damage in these patients.     

基于体素的遗忘型轻度认知障碍和轻度阿尔茨海默病全脑白质MR扩散张量成像分析

Objective To evaluate the microstructural integrity of white matter (WM) in patients with amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD) using voxel-based analysis (VBA), and investigate the relationship between WM abnormalities and gray matter(GM) atrophy.Methods Thirty-three cases with aMCI, 32 cases with mild AD and 31 normal aging volunteers as control subjects were scanned on a 3.0 T MR system using diffusion tensor imaging (DTI) and three-dimensional spoiled gradient-recalled(3DSPGR) sequences. Fractional anisotropy (FA) maps and morphological images were preprocessed by SPM5 and voxel-based comparisons between the 2 patient groups and the control group were performed by t test. Results Relative to the control group, patients with aMCI showed significantly reduced FA value in bilateral frontal, temporal and left occipital WM, left anterior part of cingulum, left inferior parietal lobule, and the W M adjacent to the triangular part of the right lateral ventricle(k≥20 voxels).In mild AD,significantly reduced FA value was found in bilateral hippocampal,inferior parietal lobular,frontal,temporal,and occipital WM,bilateral corpus callosum,anterior part of cingulums,the WM adjacent to the triaangular part of the bilateral lateral ventricles,left temporal stem,left thalamus,right precuneus(k≥20 voxels).Significantly reduced GM volume was found in left hippocampus,parahippocampal gyrus,lingual gyrus and superior temporal gyrus,bilateral insulae and middle temporal gyri in aMCl group whencompared with control group(k≥50 voxels).In mild AD,significantly reduced GM volume was found in bilateral hippoeampi,parahippocampal gyri,amygdalae,thalami,temporal,parietal,frontal,occipital cortex(k≥50 voxels).The pattern of areas with reduced FA differs;from that of the GM volumetric reduction.No areas with significantlv reduced FA was detected in aMCl compared with mild AD. There was no significant correlation between FA value of WM in patient groups and Mini-Mental State Examination(MMSE)scores.Conclusions Voxel-based MRI DTI analysis of whole brain white matter can objectively reveal widespread white matter abnormalities in early-stage AD.The difierence between WM FA reduction pattern and GM volumetric reduction pattern indicates that the pathological WM changes in earlyslage AD were caused by multiple mechanisms. FA did not vary significantly in patients pr0gressing from aMCI to mild AD and can hardly reflect the severitv of cognitive function damage in these patients.     

Amnestic mild cognitive impairment: structural MR imaging findings predictive of conversion to Alzheimer disease

BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) is considered by many to be a prodromal phase of Alzheimer disease (AD). We used voxel-based morphometry (VBM) to find out whether structural differences on MR imaging could offer insight into the development of clinical AD in patients with amnestic MCI at 3-year follow-up.MATERIALS AND METHODS: Twenty-four amnestic patients with MCI were included. After 3 years, 46% had progressed to AD (n = 11; age, 72.7 ± 4.8 years; women/men, 8/3). For 13 patients (age, 72.4 ± 8.6 years; women/men, 10/3), the diagnosis remained MCI. Baseline MR imaging at 1.5T included a coronal heavily T1-weighted 3D gradient-echo sequence. Localized gray matter differences were assessed with VBM.RESULTS: The converters had less gray matter volume in medial (including the hippocampus) and lateral temporal lobe, parietal lobe, and lateral temporal lobe structures. After correction for age, sex, total gray matter volume, and neuropsychological evaluation, left-sided atrophy remained statistically significant. Specifically, converters had more left parietal atrophy (angular gyrus and inferior parietal lobule) and left lateral temporal lobe atrophy (superior and middle temporal gyrus) than stable patients with MCI.CONCLUSION: By studying 2 MCI populations, converters versus nonconverters, we found atrophy beyond the medial temporal lobe to be characteristic of patients with MCI who will progress to dementia. Atrophy of structures such as the left lateral temporal lobe and left parietal cortex may independently predict conversion.

The term “mild cognitive impairment” (MCI) was coined to describe individuals not yet fulfilling the criteria of Alzheimer disease (AD) but who evidently do not have a normal cognitive profile compared with their contemporaries.¹ The annual conversion rate of patients with MCI is generally believed to be around 15%–20%, meaning that in 3 years, half of the patients with MCI will probably develop clinical AD.² If drugs become available that could influence the course of the disease, it is evident that these should be administered at the earliest stage at which a diagnosis can be made with certainty. Hence, clinical, biologic, and imaging markers are needed to detect that earliest stage of underlying pathology.Previous MR imaging studies assessing the predictive value of structural brain changes for AD focused on medial temporal lobe atrophy (MTA).^3,4 Brains of patients with AD exhibit more atrophy in the medial temporal lobe, thalamus, superior temporal gyrus, parietal association cortex, and cingulate gyrus than brains in patients with MCI.^5-8 Some of these brain atrophy locations might provide additional independent information about risk of conversion⁹; conversion from MCI to AD has already been associated with hippocampal and entorhinal volume loss¹⁰ and with hippocampal shape changes.¹¹ We adopted a longitudinal approach in which we followed up a study group for 3 years and then compared the baseline MR imaging scans. Voxel-based morphometry (VBM) was chosen as the postprocessing method to avoid a priori hypotheses.     

Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging: initial experience

PURPOSE: To prospectively determine if pulsed arterial spin-labeling perfusion magnetic resonance (MR) imaging depicts regional cerebral hypoperfusion in subjects with Alzheimer disease (AD) and mild cognitive impairment (MCI), compared with perfusion in cognitively normal (CN) subjects, that is consistent with results of fluorodeoxyglucose (FDG) positron emission tomography (PET) and hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) studies of similar populations. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Twenty subjects with AD (13 men, seven women; mean age, 72.9 years), 18 with MCI (nine men, nine women; mean age, 73.3 years), and 23 CN subjects (10 men, 13 women; mean age, 72.9 years) underwent arterial spin-labeling and volumetric T1-weighted structural MR imaging. Perfusion images were coregistered to structural images, corrected for partial volume effects (PVEs) with information from the structural image to determine tissue content of perfusion voxels, and normalized to a study-specific template. Analyses of perfusion differences between groups, with and without corrections for PVEs, were performed on a voxel-by-voxel basis with a one-tailed fixed-effects analysis of covariance model adjusted for age. In addition, tests were performed with and without accounting for global perfusion. RESULTS: The AD group showed significant regional hypoperfusion, compared with the CN group, in the right inferior parietal cortex extending into the bilateral posterior cingulate gyri (P <.001), bilateral superior and middle frontal gyri (P <.001), and left inferior parietal lobe (P=.007). When PVEs from underlying cortical gray matter atrophy were accounted for, the AD group still showed hypoperfusion in the right inferior parietal lobe extending into the bilateral posterior cingulate gyri (P <.001) and left (P=.003) and right (P=.012) middle frontal gyri. With a more liberal voxel-level threshold of P <.01, the MCI group showed significant regional hypoperfusion relative to the CN group in the inferior right parietal lobe (P=.046), similar to the region of greatest significance in the AD group. CONCLUSION: Arterial spin-labeling MR imaging showed regional hypoperfusion with AD, in brain regions similar to those seen in FDG PET and HMPAO SPECT studies of similar populations; this hypoperfusion persists after accounting for underlying cortical gray matter atrophy.     

阿尔茨海默病与轻度认知功能障碍的磁共振成像研究进展

本文综述了近些年阿尔茨海默病与轻度认知功能损害在磁共振成像脑结构测量、弥散成像、波谱成像及功能成像等方面的研究,旨在对其早期临床诊断及治疗提供参考。     

MR磁敏感加权成像评价轻度认知障碍者的脑内微出血和铁沉积

目的探讨MR磁敏感加权成像是否有助于在基线水平预测认知的下降。材料与方法本项前瞻性研究得到学术审查委员会批准,所有病人均签署知情同意书。本研究包     

扩散张量成像在遗忘型轻度认知障碍和Alzheimer病中的应用

目的：探讨磁共振扩散张量成像（DTI）在遗忘型轻度认知障碍（AMCI）、Alzheimer病（AD）诊断中的作用。方法：对20名aMCI患者、20名AD患者、20名正常对照者（NC）行DTI检查,分别在颞叶白质、顶叶白质、海马、胼胝体膝部及压部、上纵束Ⅱ、扣带束测ROI的FA值和ADC值。结果：NC组与aMCI组、aMCI组与AD组比较扣带束FA值均有显著性差异（P〈0．05）;NC组与AD组比较颞叶、海马、胼胝体膝部、扣带束FA值,颞叶、海马ADC值有显著性差异（P〈0．05）。结论：aMCI患者扣带束FA值异常降低;AD患者颞叶、海马、胼胝体膝部、扣带束FA值降低和颞叶、海马ADC值增高,提示DTI检查有助于aMCI、AD患者的早期诊断。     

Proton MR spectroscopy in mild cognitive impairment and Alzheimer disease: comparison of 1.5 and 3 T

BACKGROUND AND PURPOSE: Theoretically, proton ((1)H) MR spectroscopy at a higher field strength has the advantages of higher signal-to-noise ratio and improved spectral resolution. We therefore compared the ability of single-voxel (1)H MR spectroscopy at 1.5 and 3 T to diagnostically discriminate among cognitively normal elderly subjects, patients with mild cognitive impairment (MCI), and patients with Alzheimer disease (AD). METHODS: At both 1.5 and 3 T, we studied 41 cognitively normal elderly subjects, 20 patients with MCI, and 20 patients with AD. In each subject, (1)H MR spectroscopy was performed at TEs of 30 and 135 ms and from voxels placed over the posterior cingulate gyri. RESULTS: Average line widths and interexamination variability of metabolite ratios were higher at 3 T than at 1.5 T. Consistent quantification of glutamine (Gln) + glutamate/creatine (Cr) and Gln/Cr peak ratios occurred at 3 T but not at 1.5 T. Choline (Cho)/Cr (at TE = 135 ms) and myo-inositol (MI)/Cr were higher and N-acetylaspartate (NAA)/Cr (at TE = 135 ms) and NAA/MI were lower in patients with MCI than in cognitively normal subjects only at 1.5 T. MI/Cr and Cho/Cr were higher and NAA/Cr and NAA/MI were lower in patients with AD than in cognitively normal subjects at both 1.5 and 3 T. Differentiation of patients with AD from cognitively normal subjects by using the NAA/MI data was similar at both field strengths (P >.05). CONCLUSION: With currently available technology, the diagnostic performance of (1)H MR spectroscopy in patients with MCI and those with AD was not better at 3 T than at 1.5 T.     

静息状态下MR功能成像大型网络分析对阿尔茨海默病、轻度认知障碍和正常认知状态的分类

目的应用大型网络(LSN)分析对阿尔茨海默病(AD)、遗忘型轻度认知功能障碍(aMCI)和认知正常(CN)的受检者进行分类。材料与方法本研究遵守HIPAA并经机构伦理委员会认可,每名参与者均签署书面知情同意书。55例     

Cortical deactivation in mild cognitive impairment: high-field-strength functional MR imaging

PURPOSE: To prospectively identify brain regions in which task-related changes in activation during a memory encoding task, measured with functional magnetic resonance (MR) imaging, correlate with degree of memory impairment across Alzheimer disease (AD), mild cognitive impairment (MCI), and elderly control subjects. MATERIALS AND METHODS: The institutional review board approved this HIPAA-compliant study, and each patient gave written informed consent. Seventy-five subjects (mean age, 72.9 years+/-7.2 [standard deviation]; 37 men, 38 women)-13 patients with mild AD, 34 individuals with amnestic MCI, and 28 healthy elderly control subjects-were imaged at 4.0 T during novel encoding (NE) and familiar encoding (FE) of face-name pairs presented within a block design for later retrieval. Blood oxygen level-dependent (BOLD) changes were assessed across the entire brain for each group. Between-subject analysis identified brain regions demonstrating a monotonic increase or decrease in activation magnitude, from control subjects to patients with MCI to patients with mild AD. BOLD response was also correlated with score on the delayed portion of the California Verbal Learning Test (CVLT). RESULTS: In controls, the task elicited positive activation (NE>FE) in the dorsolateral prefrontal, lateral parietal, and medial temporal regions, and negative activation (FE>NE) in the midline frontal and parietal regions. Along the spectrum from control subjects to patients with AD, there was decreasing activation in the medial temporal lobe (MTL), including the hippocampus and parahippocampal and fusiform gyri, and increasing activation in the posteromedial cortices (PMCs), primarily in the precuneus and posterior cingulate gyrus. Activation magnitude in the PMCs significantly (P<.001, r=-0.502) correlated with CVLT score. CONCLUSION: Compared with activation in the MTL, deactivation in the PMCs could be a more sensitive marker of early AD at functional MR imaging.     

Alzheimer disease: measuring loss of cerebral gray matter with MR imaging

The distributions of the cerebral gray matter, the white matter, and the intracranial cerebrospinal fluid (CSF) were measured in 14 patients with Alzheimer disease (AD) and in 14 healthy control subjects. The measurements, derived from two specifically designed magnetic resonance inversion-recovery sequences, compensate for partial signal averaging. The percentage of the gray matter in the brains of AD patients (44.9% +/- 4.4) was significantly lower than in control subjects (50.2% +/- 3.2). The most significant reduction (P less than .001) occurred in the temporal lobes (13.8%) and a central region (12.8); the reduction in frontal lobe (11.2%) and occipital lobe (9.2%) was also statistically significant (P less than .01). There was an increase in the CSF volume in the temporal, occipital, and frontal regions; no region showed a significant difference in the white matter content. The findings of diffuse changes and temporal lobe involvement in AD are consistent with pathologic observations of cortical cell loss.