阿尔茨海默病与轻度认知障碍弥散张量成像研究

目的:应用磁共振弥散张量成像技术(DTI)研究阿尔茨海默病(AD)与轻度认知障碍患者(MCI)脑白质损伤情况。方法:对21例AD患者、15例MCI患者和20名健康志愿者进行脑部DTI扫描后,测量双脑区感兴趣区的各向异性分数值(FA)且进行比较。结果:AD患者额叶、顶叶、颞叶和胼胝体的FA值与MCI组和对照组均存在显著性差异,MCI患者仅颞叶和胼胝体的FA值与对照组均存在显著性差异。结论:AD患者与MCI患者存在脑白质结构的差异,DTI技术能够在一定程度上提供MCI的早期诊断指标。     

弥散张量成像在轻度认知功能障碍中的应用

轻度认知功能障碍（MCI）目前已经成为严重影响老年人健康的疾病,早期具有可逆性。近年来弥散张量成像（DTI）以其定量显示脑白质纤维束的优势,越来越多的应用于临床,成为了研究的热点。目前研究表明,MCI患者海马、穹隆、扣带回和胼胝体的DTI指标变化明显,可用于MCI的早期识别和病情评估及预测,且多个指标联用可能增加其准确性。MCI患者DTI表现与认知功能的下降程度具有相关性,尤其与记忆功能的相关性较为确定。MCI亚型中,遗忘型MCI （aMCI）发展为阿尔茨海默病（AD）的风险更高,其部分各向异性（FA）值越低、平均弥散度（ADC）值越高预示着转化为AD的可能性越大;DTI技术对AD与MCI患者脑白质的差异较为灵敏,AD的脑白质病变范围更广、程度更重。但目前关于DTI在MCI中的应用尚存在诸多问题,尚需进一步研究。     

Diffusion tensor imaging based white matter changes and antioxidant enzymes status for early identification of mild cognitive impairment

Mild cognitive impairment (MCI) is an early stage of dementia. The changes in white matter integrity and antioxidant enzymes levels are crucial in onset and progression to Alzheimer’s disease (AD). To elucidate the changes in cognitive performance, white matter integrity, oxidative stress marker, for early detection of prodromal state of AD. Fifty cases of MCI and controls (55-75 years) were subjected to Mini Mental State Examination (MMSE), diffusion tensor imaging (DTI) followed by estimation of superoxide dismutase, glutathione peroxidase and lipid peroxidation in serum of MCI and control population. The MMSE scores of MCI subjects were (28±2 - 22.6±1) as compared with controls (28±1- 29±1). DTI metrics fractional anisotropy (FA) values in right and left frontal lobe, fornix, corpus callosum, while apparent diffusion coefficient (ADC) values in right temporal lobe, hippocampus head, corpus callosum right, and forcep major were significantly altered in MCI as compared with controls. Superoxide dismutase, glutathione peroxidase level were lower while lipid peroxidation marker malondialdehyde (MDA) was increased in patients with MCI as compared with controls. The study emphasized that changes in neuro-psychological performance, white matter integrity and antioxidant enzymes level provide early signature for diagnosis of MCI.     

弥散张量成像技术预测遗忘型轻度认知障碍患者向老年性痴呆转化的随访研究

目的:探讨弥散张量成像技术(diffusion tensor imaging,DTI)对遗忘型轻度认知功能障碍(aMCI)向老年性痴呆(AD)转化的预测作用。方法:41例aMCI患者(aMCI组)常规予核磁共振(MRI)和DTI扫描,测定感兴趣区的各向异性分数(fractional anisotropy,FA)和表观扩散系数(apparent diffusion coefficient,ADC),以20名老年健康志愿者作为对照(正常对照组)并随访1~3年。结果:与正常对照组比较,aMCI组41例患者中有22例扣带束FA基线值偏低(P0.05),随访1~3年后,其中有19例转化为AD;另外19例扣带束FA值正常的aMCI患者只有2例转化为AD。与非转化AD者比较,AD转化者前额叶、颞叶、海马、下额枕束、胼胝体膝部和扣带束等部位FA值降低(P均0.01),颞叶、海马等部位ADC值升高(P均0.05)。结论:DTI技术具有预测aMCI向AD转化的作用,aMCI患者扣带束FA值低可能是aMCI向AD转化的敏感指标。     

Educational level and cognitive impairment in patients with Parkinson disease

Background and purposeParkinson disease (PD) is a risk factor for dementia. In addition, specific cognitive deficits can occur in PD patients without dementia. A patient's level of education could have an influence on the development of cognitive impairment in PD. The aim of this study was to examine the relationship between the level of education and cognitive performance in non-demented patients with PD.Material and methodsThirty-seven consecutive, nondemented PD patients and 40 healthy controls fulfilled the inclusion criteria and were enrolled in the case-control study. Each of the controls and PD patients were classified, for the purpose of this study, into one of three groups (low, intermediate, higher), categorized by the number of years of education. There were no differences in education and age between the controls and PD patients. All of the subjects were evaluated with a battery of neuropsychological tests: Mini-Mental State Examination, Trail Making Tests, Stroop Test, Mental Rotation Test, and Verbal Fluency Test.ResultsLess (low and intermediate) education was correlated with poor results from tests. The comparison of all groups of PD patients and controls demonstrated that PD subjects received lower test scores, especially for the low and intermediate groups. However, no statistically significant difference was reached between educationally advanced PD patients and the appropriate control subjects.ConclusionsAs compared to the controls, most non-demented PD patients presented executive-type cognitive dysfunction. The higher educational level, however, was associated with a lower risk of cognitive deterioration. We conclude that higher education might have protective effects in cognitive decline in PD.     

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。     

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.     

Cerebral small vessel disease affects white matter microstructure in mild cognitive impairment

Microstructural white matter deterioration is a frequent finding in mild cognitive impairment (MCI), potentially underlying default mode network (DMN) dysfunctioning. Thus far, microstructural damage in MCI has been attributed to Alzheimer's disease pathophysiology. A cerebrovascular role, in particular the role of cerebral small vessel disease (CSVD), received less interest. Here, we used diffusion tensor imaging (DTI) to examine the role of CSVD in microstructural deterioration within the normal appearing white matter (NAWM) in MCI. MCI patients were subdivided into those with (n = 20) and without (n = 31) macrostructural CSVD evidence on MRI. Using TBSS we performed microstructural integrity comparisons within the whole brain NAWM. Secondly, we segmented white matter tracts interconnecting DMN brain regions by means of automated tractography segmentation. We used NAWM DTI measures from these tracts as dependent variables in a stepwise‐linear regression analysis, with structural and demographical predictors. Our results indicated microstructural deterioration within the anterior corpus callosum, internal and external capsule and periventricular white matter in MCI patients with CSVD, while in MCI patients without CSVD, deterioration was restricted to the right perforant path, a tract along the hippocampus. Within the full cohort of MCI patients, microstructure within the NAWM of the DMN fiber tracts was affected by the presence of CSVD. Within the cingulum along the hippocampal cortex we found a relationship between microstructural integrity and ipsilateral hippocampal volume and the extent of white matter hyperintensity. In conclusion, we found evidence of CSVD‐related microstructural damage in fiber tracts subserving the DMN in MCI. Hum Brain Mapp 35:2836–2851, 2014. © 2013 Wiley Periodicals, Inc .     

老年认知功能损害的脑诱发电位研究

目的：探讨阿尔茨海默病（AD）和老年轻度认知功能损害（MCI）的脑诱发电位（BEPs）变化。方法：用美国Nicolet Spirit脑电生理仪记录24例AD病人（AD组）和23例MCI患者（MCI组）的脑干听觉反应（ABR）、关联性负变（CNV）、P300和视觉诱发电位（VEP），并与29名认知功能正常的老年人（NC组）进行比较。结果：（1）3组间大部分的BEPs检测指标的差异有显著性，AD组与NC组之间差异有显著性的指标比AD组与MCI组之间要多；（2）MCI与NC组相比，MCI组的ABR波V绝对波幅和P300的P3靶波幅显著降低；（3）多元逐步判别分析，ABR波Ⅲ绝对潜伏期及绝对波幅、波V对波幅及绝对潜伏期、CNV的反应时间和P300的P3靶波幅具有显著性判别意义，3组的判别总正确率为84.2%。结论：多项BEPs检测有助于AD的诊断，ABR的波V绝对波幅和P300的P3靶波幅显著降低具有早期诊断价值。     

Illustration of dynamic changes in Alzheimer pathology: From mild cognitive impairment to terminal stage

It is quite important to examine the neuropathology of large numbers of brains from non‐demented as well as demented subjects to elucidate the pathogenesis of dementia. Such a study, “power neuropathology” reveals the temporal profile of the disease, and results in the development of the treatment and the prevention of dementia.     

Impact of perceived stress on cognitive performance: Moderating effect of mild cognitive impairment and Alzheimer’s disease

Introduction: Stress is a well-known determinant of cognitive performance in both younger and older adults. However, the moderating effect of pathological aging on this relationship remains insufficiently documented. We hypothesize that mild cognitive impairment (MCI) and Alzheimer’s disease (AD) patients will report higher perceived stress than control older adults, when asked to complete an effortful cognitive task. We also hypothesize that the deleterious effect of perceived stress on cognitive performance is more evident in MCI and AD patients.

Method: The 131 participants consisted of: 25 functional older adults, 35 nonamnestic-MCI patients, 35 amnestic-MCI patients, and 36 AD patients. They were asked to complete the Victoria Stroop test and report their level of perceived stress at four times: before the test (i.e., baseline) and after each part of the test (three, increasingly effortful levels of cognitive requirement).

Results: Overall, perceived stress increased in the most effortful condition—except for AD patients, who reported a decline. A positive main effect of perceived stress on response latency was confirmed. However, this effect became negative in all participants when the model accounted for the difficulty of the task.

Discussion: The results suggest that the ability to perceive the stress levels generated by an effortful cognitive task may be altered in AD. They also suggest that the Stroop task may generate a form of perceived stress favoring engagement, and AD patients may not benefit from its positive effects on performance. They put into questions the usual clinical interpretations.     

Semantic knowledge in mild cognitive impairment and mild Alzheimer's disease

The aim of this study was to investigate memory in patients with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Ten patients with MCI, 11 with AD and a group of age and education matched healthy control participants were assessed on a comprehensive battery of semantic memory tests, including traditional semantic memory measures and a non-verbal test of knowledge of object use. The MCI group was impaired on tests of category fluency and all three conditions of an object knowledge test (matching to recipient, function and action), plus a difficult object-naming test. The mild AD group showed additional impairments on traditional measures of semantic memory, including naming high frequency items, comprehension and semantic association. Together these findings suggest that semantic memory impairments occur early in the course of AD, more specifically in patients with "amnesic" MCI, and provide further evidence that impaired category fluency reflects semantic breakdown.     

Defining mild cognitive impairment in Parkinson's disease

Our purpose was to characterize a state of mild cognitive impairment (MCI) in Parkinson's disease (PD) (PD‐MCI) that would be analogous to the MCI that is posited as a precursor of Alzheimer's disease (AD). We categorized 86 PD subjects in a brain bank population as either cognitively normal (PD‐CogNL), PD‐MCI using criteria that included a 1.5 standard deviation or greater deficit upon neuropsychological testing consistently across at least one cognitive domain without dementia, and PD dementia (PD‐D) using DSM‐IV criteria. Twenty‐one percent of our PD sample met criteria for PD‐MCI, 62% were PD‐CogNL, and 17% had PD‐D. The mean duration of PD and MMSE scores of the PD‐MCI group were intermediate and significantly different from both PD‐CogNL and PD‐D. The cognitive domain most frequently abnormal in PD‐MCI was frontal/executive dysfunction followed by amnestic deficit. Single domain PD‐MCI was more common than PD‐MCI involving multiple domains. We conclude that a stage of clinical cognitive impairment in PD exists between PD‐CogNL and PD‐D, and it may be defined by applying criteria similar to the MCI that is posited as a precursor of AD. Defining PD‐MCI offers an opportunity for further study of cognitive impairment in PD and targets for earlier therapeutic intervention. © 2007 Movement Disorder Society     

Brain imaging of mild cognitive impairment and Alzheimer’s disease

The rapidly increasing prevalence of cognitive impairment and Alzheimer’s disease has the potential to create a major worldwide healthcare crisis. Structural MRI studies in patients with Alzheimer’s disease and mild cognitive impairment are currently attracting considerable interest. It is extremely important to study early structural and metabolic changes, such as those in the hippocampus, entorhinal cortex, and gray matter structures in the medial temporal lobe, to allow the early detection of mild cognitive impairment and Alzheimer’s disease. The microstructural integrity of white matter can be studied with diffusion tensor imaging. Increased mean diffusivity and decreased fractional anisotropy are found in subjects with white matter damage. Functional imaging studies with positron emission tomography tracer compounds enable detection of amyloid plaques in the living brain in patients with Alzheimer’s disease. In this review, we will focus on key findings from brain imaging studies in mild cognitive impairment and Alzheimer’s disease, including structural brain changes studied with MRI and white matter changes seen with diffusion tensor imaging, and other specific imaging methodologies will also be discussed.     

弥散张量成像与老年人认知功能的相关性

目的：研究老年人认知功能与MRI弥散张量成像（DTI）参数的相关性。方法：年龄〉60岁的老年人43例,按其认知功能量表评分[简易智能状态量表（MMSE）、临床痴呆量表（CDR）、总体衰退量表（GDS）和日常生活活动能力量表（ADL）]分为认知功能正常组、轻度认知功能障碍组和阿尔茨海默病3组,比较各组间头颅MRI部分各向异性（FA）和表观弥散系数（ADC）值是否具有差异,寻找与认知功能相关的颅内结构。结果：左侧颞叶、胼胝体膝部、压部的FA和ADC值,以及右侧额叶、双侧半卵圆中心的ADC值组间差异有统计学意义（P〈0.05）。FA值随认知功能减退而降低;而ADC值随认知功能减退而增高。额叶、颞叶、半卵圆中心和胼胝体等部位的DTI参数与常用的MMSE、CDR、GDS、ADL评分显著相关（P〈0.05）。结论：MRIDTI参数与老年人认知功能水平显著相关。     

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。     

CERAD test performances in amnestic mild cognitive impairment and Alzheimer's disease

OBJECTIVES: The aim of the study was to examine the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test performances cross-sectionally in patients suffering from amnestic mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Moreover, we wanted to determine the sensitivity to amnestic MCI and mild AD, as well as the specificity of different CERAD subtests in our study groups. MATERIAL AND METHODS: Fifteen healthy elderly individuals, 15 amnestic MCI patients and 15 probable AD patients suffering from mild dementia were tested with the CERAD neurocognitive dementia screening test. RESULTS: Significant differences were found in all CERAD tests except Constructional praxis (copy) and Clock drawing between the controls and the AD group. The MCI group was differentiated from the controls only in the Wordlist learning test. In the language tests the sensitivity to MCI and AD was quite low and the specificity very high. In the savings scores the sensitivity to AD was high, but the specificity rather low. The Wordlist recognition test screened no false positives using the current cut-off score and the sensitivity to AD was 0.6, but only one MCI patient was detected using the current cut-off score. Raising the cut-off score also raised the sensitivity to MCI without dramatic loss of specificity. Cut-off scores for the Wordlist learning test and Wordlist delayed recall, which have been found to differentiate normal aging from dementia, are lacking in the Finnish CERAD. The current data indicates that the Wordlist learning test might be relatively sensitive to MCI. CONCLUSIONS: The results indicate that the Finnish CERAD test battery with its current cut-off scores has low sensitivity to MCI, and using it as a sole cognitive screening instrument for MCI and preclinical dementia might result in false negatives.