脑白质病变与轻度认知功能障碍的关系

目的 探讨脑白质病变(WML)与轻度认知功能障碍(MCI)的关系.方法 71例WML患者根据头颅MRI检查分为轻度组(27例)、中度组(21例)、重度组(23例),39例无WML的对照者为对照组.对入组者进行神经心理学量表检查;比较各组MCI的患病率,分析WML与MCI的相关性.结果 WML轻、中、重度组的MCI患病率明显高于对照组(均P＜0.01);WML中、重度组简易精神状态检查(MMSE)及蒙特利尔认知评估量表(MoCA)评分显著低于WML轻度组和对照组(均P＜0.01);随着WML程度的加重,除了抽象能力评分,MoCA其他各认知领域的评分均显著降低(均P＜0.05).多元线性相关分析显示,WML程度与MMSE、MoCA总分及除抽象思维能力的各认知域评分呈负相关(r=-0.252 ～-0.782,均P＜0.01).结论 WML可导致MCI,其对认知功能障碍的影响与WML的程度有关.     

Differences in grey and white matter atrophy in amnestic mild cognitive impairment and mild Alzheimer's disease

Background:  Grey matter (GM) atrophy has been demonstrated in amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD), but the role of white matter (WM) atrophy has not been well characterized. Despite these findings, the validity of aMCI concept as prodromal AD has been questioned.
Methods:  We performed brain MRI with voxel-based morphometry analysis in 48 subjects, aiming to evaluate the patterns of GM and WM atrophy amongst mild AD, aMCI and age-matched normal controls.
Results:  Amnestic mild cognitive impairment GM atrophy was similarly distributed but less intense than that of mild AD group, mainly in thalami and parahippocampal gyri. There were no difference between aMCI and controls concerning WM atrophy. In the mild AD group, we found WM atrophy in periventricular areas, corpus callosum and WM adjacent to associative cortices.
Discussion:  We demonstrated that aMCI might be considered a valid concept to detect very early AD pathology, since we found a close proximity in the pattern of atrophy. Also, we showed the involvement of WM in mild AD, but not in aMCI, suggesting a combination of Wallerian degeneration and microvascular ischaemic disease as a plausible additional pathological mechanism for the discrimination between MCI and AD.     

轻度认知功能障碍与脑白质弥散张量成像的相关性研究

目的通过磁共振弥散张量成像研究不同区域脑白质损害与轻度认知功能(MCI)的关系。方法纳入2015年7月至2016年2月我院的住院患者56例为研究对象,其中MCI组34例,认知功能正常组22例。所有研究对象进行一般情况检查,完成神经心理学量表检测。通过头颅磁共振弥散张量成像(DTI)检查对不同脑区白质纤维进行部分各向异性(FA)值测量。结果 MCI组患者与认知功能正常组相比,右侧额叶FA值(0.335±0.068)、左侧颞叶白质FA值(0.391±0.032)及胼胝体膝部FA值(0.658±0.053)降低,差异具有统计学意义(P0.05)。将上述FA值和MMSE、Mo CA量表中各认知域进行典型相关分析,结果显示右侧额叶白质FA值与注意与计算力呈正相关,左侧颞叶白质和胼胝体膝部FA值与记忆力呈正相关(P0.05)。结论 MCI患者注意与计算力的障碍可能与右侧额叶白质损害有关,而左侧颞叶白质及胼胝体膝部白质的损害可能导致早期的记忆障碍。DTI可能成为超早期识别与诊断MCI的新方法。     

轻度认知障碍患者视空间功能的fMRI研究

目的 :探索早期诊断Alzheimer病的方法。 方法 :对轻度认知障碍 (MCI)患者和正常对照各 9名在fMRI下进行指针位置辨别的视空间功能测试。结果 :MCI患者比正常对照的反应时间延长 ,正确率降低 ,脑激活图显示MCI患者比正常对照在双侧顶叶 ,颞枕交界处和视觉皮层的激活强度显著减弱 (P <0 .0 5 ) ,范围减小 ,而在右侧额中回的激活代偿性增强。结论 :MCI患者视空间功能受损 ,这可通过fMRI来加以检测。     

Clinical significance of subcortical vascular disease in patients with mild cognitive impairment

Patients with mild cognitive impairment (MCI) typically present with memory complaints. Some of these patients have subcortical vascular disease on computed tomography (CT) scan, namely white matter changes and lacunar infarcts, however it is not known whether these findings are associated with more pronounced cognitive deficits. In the present study we compare demographic, clinical and neuropsychological characteristics of MCI patients according to the presence or the absence of subcortical vascular disease. Forty consecutive patients with memory complaints, at least one neuropsychological memory test below 1 SD the normal for age and education, and maintained activities of daily living, were included. Patients with dementia, history of stroke or transient ischemic attack, or other brain disorders, were excluded. Twenty-five (62.5%) patients with MCI had no ischemic lesions on CT scan, and 15 (37.5%) were found to have subcortical vascular changes. MCI patients with subcortical vascular changes were older (77.1 +/- 6.8 vs. 70.8 +/- 7.5 years old), and more often males. The number of vascular risk factors, the frequency of neurological signs, the Hachinski score and the neuropsychological tests scores were not significantly different. The presence of subcortical vascular disease on CT scan is frequent in older patients with MCI, but does not appear to be associated with the severity of cognitive deficits.     

Executive dysfunction and periventricular diffusion tensor changes in amnesic mild cognitive impairment and early Alzheimer's disease

Our aim in this study was to explore the neural substrates of executive function in frontal and nonfrontal white matter using diffusion tensor imaging (DTI). We studied the relationship between executive dysfunction and DTI measurements on 13 subjects with amnesic mild cognitive impairment (aMCI), 11 subjects with early Alzheimer's disease (AD), and 16 control subjects. All participants underwent an examination of their intelligence, memory, and executive function and were subjected to DTI. Both aMCI and early AD subjects showed executive function impairment with differential performance in frontal‐related behaviors. Both aMCI and early AD subjects showed increased mean diffusivity in the genu of the corpus callosum and left frontal periventricular white matter (PVWM), whereas subjects with early AD showed an additional decrease in the fractional anisotropy of bilateral frontal PVWM and in the genu of the corpus callosum. The frontal PVWM was associated with performance on the Verbal Fluency Test, the Wisconsin Card Sorting Test (WCST), and Part B of the Trail Making Test. The parietal PVWM was associated with perseverative errors on the WCST and Part A of the Trail Making Test. In summary, executive function was impaired in subjects with aMCI and early AD and was associated with frontal and parietal PVWM changes. These changes may be due to early AD degeneration of the lateral cholinergic projections or to early change of the superior longitudinal fasciculus. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Orientational changes of white matter fibers in Alzheimer's disease and amnestic mild cognitive impairment

White matter abnormalities represent early neuropathological events in neurodegenerative diseases such as Alzheimer''s disease (AD), investigating these white matter alterations would likely provide valuable insights into pathological changes over the course of AD. Using a novel mathematical framework called “Director Field Analysis” (DFA), we investigated the geometric microstructural properties (i.e., splay, bend, twist, and total distortion) in the orientation of white matter fibers in AD, amnestic mild cognitive impairment (aMCI), and cognitively normal (CN) individuals from the Alzheimer''s Disease Neuroimaging Initiative 2 database. Results revealed that AD patients had extensive orientational changes in the bilateral anterior thalamic radiation, corticospinal tract, inferior and superior longitudinal fasciculus, inferior fronto‐occipital fasciculus, and uncinate fasciculus in comparison with CN. We postulate that these orientational changes of white matter fibers may be partially caused by the expansion of lateral ventricle, white matter atrophy, and gray matter atrophy in AD. In contrast, aMCI individuals showed subtle orientational changes in the left inferior longitudinal fasciculus and right uncinate fasciculus, which showed a significant association with the cognitive performance, suggesting that these regions may be preferential vulnerable to breakdown by neurodegenerative brain disorders, thereby resulting in the patients'' cognitive impairment. To our knowledge, this article is the first to examine geometric microstructural changes in the orientation of white matter fibers in AD and aMCI. Our findings demonstrate that the orientational information of white matter fibers could provide novel insight into the underlying biological and pathological changes in AD and aMCI.     

Progression to vascular dementia of patients with mild cognitive impairment: relevance of mild parkinsonian signs

Mild parkinsonian signs (MPS) may be found among patients presenting with mild cognitive impairment (MCI), but few data are available about the relation of these signs with the prospective risk for dementia. Our retrospective investigation considered a case-series of 119 MCI subjects followed over a three-year period: their baseline clinical picture has been analyzed in search of correlation between the cognito-motor profile and the final diagnosis. The population included 66 patients with amnesic MCI and 53 with an involvement of other cognitive areas (nonamnesic MCI). MPS were detected in 22 subjects (18.5%). At the first observation, MPS cases showed an higher frequency of nonamnesic MCI and more pronounced deficits at the Trail Making Test (p < 0.05). After a three-year follow-up, 48 patients had converted to dementia. The presence of MPS at the baseline evaluation was significantly related to the development of a vascular-type dementia. The study investigates the association between MPS and MCI and might indicate for these cases a greater risk for an involvement of executive functions and the subsequent development of vascular dementia.     

Brain perfusion correlates of medial temporal lobe atrophy and white matter hyperintensities in mild cognitive impairment

Abstract Objective To assess the association of Medial Temporal lobe Atrophy (MTA) and White Matter Hyperintensities (WMHs) with gray matter perfusion in Mild Cognitive Impairment (MCI). Methods 56 MCI patients (age = 69.3 ± 7.0, 32 females) underwent brain MR scan and ^99mTc ECD SPECT. We evaluated MTA according to Scheltens' fivepoint scale on T1 MR images, and assessed WMHs using the rating scale for age-related white matter changes on T2-weighted and FLAIR MR images. We divided MCI into age-matched subgroups with high and low MTA and high and low WMHs load. We processed SPECT images with SPM2 following an optimized protocol and performed a voxel-based statistical analysis comparing high vs. low MTA and high vs. low WMHs, setting p-value at 0.001 uncorrected, thresholding cluster extent at 100 voxels, using proportional scaling and entering age and WMHs or MTA respectively as nuisance covariates. Results MCI with high compared with low MTA showed hypoperfusion in the left hippocampus and in the left parahippocampal gyrus. MCI with high compared with low WMHs showed a hypoperfusion area in the left insular region and superior temporal gyrus. Conclusions MTA in MCI is associated with hippocampal gray matter hypoperfusion while WMHs is associated with gray matter hypoperfusion in areas of the insula and temporal neocortex. These results confirm that MTA is associated with local functional changes and suggest that WMHs may be associated with remote brain cortical dysfunction.     

White matter vascular lesions are related to parietal-to-frontal coupling of EEG rhythms in mild cognitive impairment

Do cerebrovascular and Alzheimer's disease (AD) lesions represent additive factors in the development of mild cognitive impairment (MCI) as a putative preclinical stage of AD? Here we tested the hypothesis that directionality of fronto‐parietal functional coupling of electroencephalographic (EEG) rhythms is relatively preserved in amnesic MCI subjects in whom the cognitive decline is mainly explained by white‐matter vascular load. Resting EEG was recorded in 40 healthy elderly (Nold) and 78 amnesic MCI. In the MCI subjects, white‐matter vascular load was quantified based on magnetic resonance images (0–30 visual rating scale). EEG rhythms of interest were δ (2–4 Hz), θ (4–8 Hz), α1 (8–10.5 Hz), α2 (10.5–13 Hz), β1 (13–20 Hz), and β2 (20–30 Hz). Directionality of fronto‐parietal functional coupling of EEG rhythms was estimated by directed transfer function software. As main results, (i) fronto‐parietal functional coupling of EEG rhythms was higher in magnitude in the Nold than in the MCI subjects; (ii) more interestingly, that coupling was higher at θ, α1, α2, and β1 in MCI V+ (high vascular load; N = 42; MMSE = 26) than in MCI V? group (low vascular load; N = 36; MMSE= 26.7). These results are interpreted as supporting the additive model according to which MCI state would result from the combination of cerebrovascular and neurodegenerative lesions. Hum Brain Mapp 2008. © 2007 Wiley‐Liss, Inc.     

半自动MRI定量方法测定脑白质高信号体积与病变定性评分的相关性

背景：在磁共振T2加权像和液体衰减反转恢复像中脑白质病变表现为白质高信号,目前对脑白质高信号体积、部位与认知功能损害的关系仍存在争议。 目的：以头颅磁共振对皮质下缺血性脑血管病患者白质高信号进行定量和定性测定,分析高信号体积和部位与认知损害的关系。 设计、时间及地点：于2007-12/2008-09在河北省人民医院神经内科完成。 对象：依据影像学诊断标准确定皮质下缺血性脑血管病53例,记录症状和体征,并进行神经心理学评估。 方法：采用美国GE公司生产的半自动1.5T MRI机对患者行头MRI扫描,定量测定脑白质高信号体积,并结合脑白质病变定性评分。 主要观察指标：分析皮质下缺血性脑血管病患者脑白质高信号体积与评分的相关性,以及白质病变与认知损害的关系。 结果：脑白质高信号体积和评分高度相关（rs=0.989, P < 0.001）,两者呈曲线关系。分层多元线性回归分析显示,白质高信号体积、白质高信号总评分的变化可以分别解释简明精神状态检查评分改变的10.5%和6.8%,前者较后者能更敏感地预测简明精神状态检查评分变化。不同区域脑白质病变中,仅基底核区白质高信号评分与简明精神状态检查评分有关（t=-2.126, P=0.039）,其他各区域白质高信号评分均非简明精神状态检查评分独立预测指标。 结论：脑白质高信号体积与评分均可应用于脑白质病变的测定,前者测定较脑白质高信号评分更敏感;皮质下缺血性脑血管病患者认知功能损害随着脑白质病变的增多,尤其是基底核区白质病变的增多而加重。     

White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy

This study investigates relationships between white matter hyperintensity (WMH) volume, cerebrospinal fluid (CSF) Alzheimer's disease (AD) pathology markers, and brain and hippocampal volume loss. Subjects included 198 controls, 345 mild cognitive impairment (MCI), and 154 AD subjects with serial volumetric 1.5‐T MRI. CSF Aβ₄₂ and total tau were measured (n = 353). Brain and hippocampal loss were quantified from serial MRI using the boundary shift integral (BSI). Multiple linear regression models assessed the relationships between WMHs and hippocampal and brain atrophy rates. Models were refitted adjusting for (a) concurrent brain/hippocampal atrophy rates and (b) CSF Aβ₄₂ and tau in subjects with CSF data. WMH burden was positively associated with hippocampal atrophy rate in controls (P = 0.002) and MCI subjects (P = 0.03), and with brain atrophy rate in controls (P = 0.03). The associations with hippocampal atrophy rate remained following adjustment for concurrent brain atrophy rate in controls and MCIs, and for CSF biomarkers in controls (P = 0.007). These novel results suggest that vascular damage alongside AD pathology is associated with disproportionately greater hippocampal atrophy in nondemented older adults. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.     

Vascular risk factors and white matter hyperintensities in patients with amnestic mild cognitive impairment

BACKGROUND: Subjects affected by aMCI are considered at high risk for AD. Nevertheless, the role of both vascular risk factors and WMH is matter of debate. PATIENTS AND METHODS: We enrolled consecutively 21 aMCI subjects according to Petersen Criteria; the study included routine screening for dementia, neuropsychological evaluation and brain MRI. Six vascular risk factors were assessed and WMH was quantified by means of a semiautomatic lesion-detection program. RESULTS: Conversion to AD, according to NINCDS-ADRDA criteria, was 47.6%. Converters tended to be more affected by the most of vascular risk factors while no difference was noted in WMH. The best predictors of conversion to AD were scores obtained at several neuropsychological examination. CONCLUSION: Our results show that criteria for aMCI identify subjects with a high risk to develop AD. WMH doesn't seem to have a role in progression from aMCI to AD, while some vascular risk factors seem to promote it.     

White matter lesions on magnetic resonance imaging in late-life depression

Objectives: The aims of the present study were to identify the frequency and severity of white matter lesions on the magnetic resonance imaging (MRI) of major depressive disorders and depression caused by cerebrovascular diseases (CVD), to evaluate the relation with cerebrovascular risk factors, and finally to understand an important cause of late‐life depression. Methods: The MRI films of 32 patients over 50 years of age (15 men and 17 women) with major depressive disorders, 25 patients (17 men and eight women) with depression caused by CVD who had scores over 24 on the mini‐mental state examination, and 25 controls (six men and 19 women) were analyzed for white matter lesions according to the modified Fazekas criteria. The cerebrovascular risk factors including hypertension, arteriosclerosis, obesity, smoking, diabetes mellitus, thyroid function abnormalities, EKG abnormality and stroke were also assessed. Results: (i) The frequency of periventricular lesions or deep white matter lesions were significantly higher in patients with depression caused by CVD and major depressive disorders than in controls; (ii) the intracerebral hyperintensities or classical infarctions were prevalent in the frontal cortex (32.0%) and basal ganglia (40.0%); (iii) among cerebrovascular risk factors, stroke (P < 0.005), hypertension (P < 0.025), EKG abnormality (P < 0.005) and smoking (P < 0.05) were significantly prevalent in the patients with depression caused by CVD and major depressive disorders as compared with controls; and (iv) the severity of white matter lesions was significantly associated with the cerebrovascular risk factors (P < 0.005) in patients over 50 years of age with major depressive disorders. Conclusions: The white matter hyperintensities on brain MRI of patients with major depressive disorders over 50 years of age were significantly associated with cerebrovascular risk factors, which suggested a vascular origin of pathogenesis of late‐life depression.