轻度认知损害患者氢质子磁共振波谱随访研究

目的回顾分析并总结轻度认知损害(MCI)患者认知功能转归及脑组织代谢物氢质子磁共振波谱(~1H-MRS)特点。方法采用简易智能状态检查量表(MMSE)和蒙特利尔认知评价量表(Mo CA)评价75例轻度认知损害患者和17例性别、年龄、受教育程度相匹配的正常对照者的认知功能,1H-MRS检测左侧海马和左侧额叶代谢物[包括N-乙酰天冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)、肌醇(m I)、谷氨酸复合物(Glx)]表达变化。结果与正常对照者相比,轻度认知损害患者左侧海马和左侧额叶Glx/Cr比值均降低(P=0.030,0.030)。至随访结束时,MCI组7例(9.33%)进展为阿尔茨海默病、55例(73.33%)认知功能无变化、13例(17.33%)逆转为认知功能正常;正常对照组13例(13/17)认知功能功能无变化,2例(2/17)进展为轻度认知损害,无一例进展为阿尔茨海默病。不同认知功能转化亚组中仅MCI-MCI组患者Glx/Cr比值高于MCI-AD组(P=0.040)。结论左侧海马和左侧额叶Glx/Cr比值降低可能是轻度认知损害患者认知功能恶化较敏感的生物学指标,尚待扩大样本量、延长随访时间深入研究。     

轻度阿尔茨海默病患者磁共振成像及磁共振氢质子波谱研究

目的　探讨磁共振成像 (magneticresonanceimaging,MR)及磁共振氢质子波谱 (1H magneticresonancespectroscopy ,1H MRS)对轻度阿尔茨海默病 (Alzheimerdisease ,AD)患者的早期诊断。方法　对 18例临床确诊轻度AD患者和 2 0名正常对照者的MR及1H MRS进行分析 :MR上观察两组的海马回钩间距 (AB)及同层颅腔左右径 (CD)并计算两者间 (AB/CD)的比值 ;对两组额、颞叶区行1H MRS检测 ,得到N 乙酰天门冬氨酸 (N acetylaspartate ,NAA)峰、肌酸 (creatine ,Cr)峰、胆碱 (choline ,Cho)峰的积分值及计算NAA/Cr、NAA/ (Cr Cho)。对 2组检测值 ( x±s)行t检验。结果　AD组的AB =(2 7 5 3± 2 1)mm ,AB/CD =(0 2 2± 0 0 5 )mm及额、颞叶的NAA分别是 32 74± 4 72和35 38± 3 5 2 ,颞叶的NAA/Cr=2 4 6± 0 4 3,与正常对照组比较均有统计学差异 (P <0 0 5 )。用ROC法找出诊断阈值并联合应用诊断早期AD ,敏感性为 87% ,特异性为 94 %。结论　海马回钩间距及其与同层颅腔左右径比值的增大 ;额、颞叶NAA的减少 ,尤其是颞叶NAA的减少有助于对轻度AD患者的早期诊断。     

DTI评价轻度认知障碍及轻中度阿尔茨海默病脑白质微细结构损害的研究

目的应用磁共振弥散张量成像(DTI)技术研究轻度认知障碍(MCI)及轻中度阿尔茨海默病(AD)患者脑白质微细结构的改变。方法对MCI患者、轻中度AD患者各12例及健康老年人12名(对照组)行常规MRI及DTI检查,测量其胼胝体压部、额叶、顶叶、颞叶、枕叶、内囊前肢及内囊后肢白质区部分各向异性分数(FA)和平均弥散率(MD)。将3组的FA、MD值进行比较,并与MMSE评分、单词回忆及单词再认评分进行相关性分析。结果 (1)MCI患者顶叶白质FA值为0.489±0.079,与对照组(0.558±0.079)相比下降(P0.05)。(2)AD患者额叶、顶叶及颞叶FA值分别为0.405±0.072、0.454±0.069和0.363±0.056,与对照组(分别为0.499±0.081、0.558±0.079和0.440±0.061)比较差异均有统计学意义(P0.05)。AD患者胼胝体压部、额叶及顶叶MD值分别为0.978±0.082、0.920±0.054和0.81 7±0.045,均高于对照组(分别为0.801±0.093、0.820±0.084、0.712±0.096)(P0.05)。AD、MCI两组内囊前、后肢及枕叶FA及MD值分别与健康对照组比较均无统计学差异(P0.05)。(3)3组顶叶、颞叶FA值与MMSE、单词回忆及单词再认评分均有相关性(分别r=0.869、-0.621、-0.759,均P0.01;r=0.446、-0.486、-0.361,均P0.05),胼胝体压部FA值与单词再认评分有相关性(r=-0.343,P0.05);3组胼胝体压部及顶叶MD值与MMSE、单词回忆及单词再认评分均有相关性(分别r=-0.612、0.547、0.586,均P0.01;r=-0.576、0.499、0.519,均P0.01),内囊前肢MD值与MMSE评分相关(r=-0.340,P0.05)。结论 MCI及轻中度AD患者存在脑白质选择性微细结构损害,且该损害出现在与高级皮层功能相关的脑区,而与初级功能相关的区域未见明显受损。     

轻度认知障碍和轻度Alzeimer病的磁共振波谱分析

目的探讨氢质子磁共振波谱（1H—MRs）在轻度认知障碍（MCI）、轻度Alzheimer病（AD）诊断与鉴别诊断中的作用。方法对20例MCI患者、20例AD患者、20例正常对照者行。H—MRS检查,采用点分辨自旋回波波谱序列（PRESS）,测定双侧内侧颞叶的N-乙酰天门冬氨酸（NAA）、胆碱（Cho）和肌醇（mI）与肌酸（Cr）的比值,并比较各组闻NAA／Cr、mI／Cr、Cho／Cr比值的差别。结果轻度AD组及MCI组与正常对照组间双侧NAA／Cr有显著性差异（P〈0．05）,MCI组、轻度AD组、正常对照组三组间双侧mI／Cr有显著性差异（P〈0．05）,三组间Cho／Cr比值差异无统计学意义。结论1H—MRs能无创性提供MCI、AD患者脑部的代谢情况,NAA／Cr降低和mI／Cr升高有助于MCI、轻度AD的早期诊断。     

轻度认知障碍和Alzheimer病的磁共振质子波谱(1H-MRS)研究

随着人口老龄化，伴随记忆力减退老年人越来越受到普遍的关注。轻度认知障碍（mild cognitive impairment，MCI）是介于正常老化和早期痴呆之间的一种过渡状态，反映一种有记忆主诉和客观认知损伤证据但又不能诊断为痴呆的临床状况，MCI患者为老年性痴呆的高危人群，特别是以记忆损害为主的遗忘型MCI常常转化为阿尔茨海默病（Alzheimer，AD），因此加强MCI的临床及基础研究有望对老年痴呆的早期诊断，早期干预有着重要的意义。     

麻痹性痴呆与阿尔茨海默病患者海马区氢质子磁共振波谱特点

目的 应用氢质子磁共振波谱(1 H-MRS)技术,探索麻痹性痴呆(GPI)患者、阿尔茨海默病(AD)患者和健康中老年人海马区代谢物水平特点.方法 纳入GPI患者35例,AD患者27例,健康中老年对照38名进行双侧海马区1 H-MRS检查,比较N-乙酰天门冬氨酸(N-acetylaspartate,NAA)/肌酸、胆碱/肌酸,NAA/胆碱,胆碱/NAA和肌醇/肌酸的水平;并同日进行简易精神状态检查(MMSE)、蒙特利尔认知检查量表(MoCA)评定,探索GPI、AD患者海马区代谢物水平与病程严重程度的相关性.结果 GPI、AD组双侧海马区的NAA/肌酸均显著低于健康对照组(左侧1.48 ±0.25、1.52±0.28和1.71 ±0.36,F=5.928,P=0.004;右侧 1.47±0.38、1.62±0.36和1.82±0.42,F=7.309,P=0.001),GPI组右侧海马区的胆碱/NAA (0.68±0.48)显著高于AD组(0.49 ±0.15)和健康对照组(0.53±0.14),差异有统计学意义(P =0.024,P=0.045).GPI组和AD组海马区各代谢物水平与MMSE、MoCA评分均无显著相关.结论 GH和AD患者均存在双侧海马区神经元损伤.     

轻度认知功能损害的磁共振波谱研究进展

轻度认知功能损害(MCI)是一种介于正常老年人和轻度痴呆之间的临床过渡状态,随着社会人口老龄化,MCI引起了越来越多的学者的关注,磁共振波谱(MRS)作为目前唯一能够无创性检测活体组织能量代谢、生化改变及化合物定量分析的一种新技术,已越来越多地应用于MCI的早期诊断与防治的研究中。本文就国内外近年来的一些研究成果作一综述。     

轻度认知障碍和阿尔茨海默病静息态功能磁共振成像研究进展

随着功能磁共振研究的不断发展,大量的研究发现轻度认知障碍（MCI）和阿尔茨海默病（AD）患者的部分脑区自发活动发生改变.这种改变包括脑区相似性的改变和不同脑区之间功能连接的改变, 主要发生于大脑默认网络（DMN）的大部分区域中.本文将近年来在这方面的研究进展进行了综述.     

轻度认知障碍的转化及相关因素研究进展

轻度认知障碍（MCI）是介于正常衰老与痴呆之间的一种过渡状态,具有发展为痴呆的高度危险性。本文将对近年MCI的转化及转化率,转化的认知功能评估、生物学指标、神经影像学、危险因素及药物干预等研究进展进行全面综述。     

阿尔茨海默病和轻度认知障碍患者脑网络变化特点的研究进展

阿尔茨海默病(AD)是一种隐匿性进展的神经退行性疾病,而轻度认知障碍(MCI)是AD发病前一个重要的临床前阶段。静息态功能磁共振(rs-f MRI)能在疾病早期反映脑网络变化,可作为研究AD及MCI的有效手段。本文综述了以rs-f MRI研究为基础的AD及MCI患者默认网络,注意网络,执行控制网络等的变化特点,为AD的早期诊断及干预提供依据。     

1H-MRS asymmetry changes in the anterior and posterior cingulate gyrus in patients with mild cognitive impairment and mild Alzheimer's disease

Alzheimer's disease (AD) is the most common cause of dementia worldwide. Amnestic mild cognitive impairment (aMCI) is often the prodromal stage to AD. Most patients with aMCI harbor the pathologic changes of AD and demonstrate transition to AD at a rate of 10%–15% per year. Patients with AD and aMCI experience progressive brain metabolite changes. Accumulating evidence indicates that the asymmetry changes of left and right brain happen in the early stage of AD. However, the features of asymmetry changes in both anterior cingulate gyrus (ACG) and posterior cingulate gyrus (PCG) are still unclear. Here, we examine the left–right asymmetry changes of metabolites in ACG and PCG. Fifteen cases of mild AD patients meeting criteria for probable AD of NINDS-ADRDA, thirteen cases of aMCI according to the Mayo Clinic Alzheimer's Disease Research Center criteria, and sixteen cases of age-matched normal controls (NC) received Proton magnetic resonance spectroscopy (¹H-MRS) for measurement of NAA/mI, NAA/Cr, Cho/Cr, and mI/Cr ratios in the PCG and ACG bilaterally. We analyzed ¹H-MRS data by paired t-test to validate the left–right asymmetry of ¹H-MRS data in the PCG and ACG. In AD, there was a significant difference in mI/Cr between the left and right ACG (P < 0.001) and the left and right PCG (P = 0.007). In aMCI, there was a significant difference in mI/Cr between the left and right ACG (P < 0.001). In NC, there were no differences in the ratio value of metabolites NAA/mI, NAA/Cr, Cho/Cr, and mI/Cr between the left and right ACG and PCG. Thus, the left–right asymmetry of mI/Cr in the ACG and PCG may be an important biological indicator of mild AD.     

Discourse changes in early Alzheimer disease,mild cognitive impairment,and normal aging

The purpose of this study was to determine the sensitivity of discourse gist measures to the early cognitive-linguistic changes in Alzheimer disease (AD) and in the preclinical stages. Differences in discourse abilities were examined in 25 cognitively normal adults, 24 adults with mild probable AD, and 20 adults with mild cognitive impairment (MCI) at gist and detail levels of discourse processing. The authors found that gist and detail levels of discourse processing were significantly impaired in persons with AD and MCI as compared with normal control subjects. Gist-level discourse processing abilities showed minimal overlap between cognitively normal control subjects and those with mild AD. Moreover, the majority of the persons with MCI performed in the range of AD on gist measures. These findings indicate that discourse gist measures hold promise as a diagnostic complement to enhance early detection of AD. Further studies are needed to determine how early the discourse gist deficits arise in AD.     

Diffusion tensor imaging in Alzheimer disease and mild cognitive impairment

A wide range of imaging studies provides growing support for the potential role of diffusion tensor imaging (DTI) in evaluating microstructural white matter integrity in Alzheimer disease (AD) and mild cognitive impairment (MCI). Our review aims to present DTI principles, post-processing and analysis frameworks and to report the results of particular studies.The distribution of AD-related white matter abnormalities is widely discussed in the light of deteriorated connectivity within certain tracts due to secondary white matter degeneration; primary alterations are also assumed to contribute to the pattern. The question whether it is more effective to assess the whole-brain diffusion or to directly concentrate on specific regions remains an interesting issue. Assessing white matter microstructure alterations, as evaluated by group-level differences of tensor-derived parameters, may be a promising neuroimaging tool for differential diagnosis between AD, MCI and other cognitive disorders, as well as being particularly helpful in the interpretation of underlying pathological processes.     

Olfactory tau pathology in Alzheimer disease and mild cognitive impairment

OBJECTIVE: To examine the occurrence of tau pathology in the olfactory system in aged subjects and its relation to the severity of Alzheimer disease (AD) pathology. MATERIAL AND METHODS: 273 autopsy cases (167 female, 106 male, aged 61-102, mean 83.2+/-4.5 SD years) underwent a standard neuropathological assessment with immuno-histochemical study of tau and Abeta amyloid in the olfactory bulb and nerve, and diagnosis of AD using established consensus criteria including Braak staging of neuritic AD pathology. RESULTS: All cases of definite AD (Braak stages 5 and 6, n = 96) showed large numbers of neuropil threads and neurofibrillary tangles, with amyloid deposits in 50%, and neuritic plaques only in two cases. Braak stage 4 (n = 73) was associated with tau pathology in the olfactory system in 90.4 and amyloid deposits in 9%, Braak stage 3 (n = 56) with mainly mild to moderate olfactory tau lesions in 44.6 and Abeta deposits in 9%. Braak stage 2 (n = 22) showed olfactory tau pathology in 36.4% without amyloid deposits, whereas Braak stages 0 and 1 (n = 25) were all negative. Olfactory tau pathology showed highly significant correlation with neuritic Braak staging in the brain, while both scores showed significant but low correlation with age. CONCLUSIONS: These data confirm previous studies demonstrating considerable tau pathology in the olfactory system in all definite AD cases, in more than 2/3 of limbic AD and in more than 1/3 of elderly individuals with or without mild cognitive impairment associated with Braak stage 2. Clinical dementia correlated with both Braak and olfactory tau scores, indicating that both are associated with a high risk of cognitive decline.     

Plasma multianalyte profiling in mild cognitive impairment and Alzheimer disease

OBJECTIVES: While plasma biomarkers have been proposed to aid in the clinical diagnosis of Alzheimer disease (AD), few biomarkers have been validated in independent patient cohorts. Here we aim to determine plasma biomarkers associated with AD in 2 independent cohorts and validate the findings in the multicenter Alzheimer's Disease Neuroimaging Initiative (ADNI). METHODS: Using a targeted proteomic approach, we measured levels of 190 plasma proteins and peptides in 600 participants from 2 independent centers (University of Pennsylvania, Philadelphia; Washington University, St. Louis, MO), and identified 17 analytes associated with the diagnosis of very mild dementia/mild cognitive impairment (MCI) or AD. Four analytes (apoE, B-type natriuretic peptide, C-reactive protein, pancreatic polypeptide) were also found to be altered in clinical MCI/AD in the ADNI cohort (n = 566). Regression analysis showed CSF Aβ42 levels and t-tau/Aβ42 ratios to correlate with the number of APOE4 alleles and plasma levels of B-type natriuretic peptide and pancreatic polypeptide. CONCLUSION: Four plasma analytes were consistently associated with the diagnosis of very mild dementia/MCI/AD in 3 independent clinical cohorts. These plasma biomarkers may predict underlying AD through their association with CSF AD biomarkers, and the association between plasma and CSF amyloid biomarkers needs to be confirmed in a prospective study.     

Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease

BACKGROUND: Immunoreactivity for several chemokines and for their related receptors has been demonstrated in resident cells of the central nervous system, and the up-regulation of some of them is associated with pathological changes found in Alzheimer disease (AD). OBJECTIVE: To determine interferon-gamma-inducible protein 10 (IP-10), monocyte chemotactic protein 1 (MCP-1), and interleukin 8 (IL-8) levels in cerebrospinal fluid (CSF) from subjects with amnestic mild cognitive impairment (MCI) and patients with AD as compared with age-matched controls. PATIENTS: Thirty-eight subjects with amnestic MCI, 36 patients with AD, and 41 age-matched subjects with noninflammatory affections of the nervous system. DESIGN: Evaluation of CSF chemokine production at time of diagnosis of MCI and AD; correlation with clinical and personal data. Longitudinal evaluation of subjects with MCI until conversion to AD. RESULTS: Cerebrospinal fluid IP-10 concentration was significantly increased in patients with MCI and mild AD but not in patients with severe AD (Mini-Mental State Examination score <15), whereas MCP-1 and IL-8 levels were increased in patients with MCI and all patients with AD. A significant positive correlation between Mini-Mental State Examination score and CSF IP-10 or MCP-1 concentration was observed in patients with AD. No correlation between IP-10 levels and age was found, whereas MCP-1 and IL-8 levels correlated positively with age. Out of 38 subjects with MCI, 19 developed AD within a 1- to 3-year follow-up. CONCLUSIONS: The presence of inflammatory molecules is likely to be a very early event in AD pathogenesis, even preceding the clinical onset of the disease, as demonstrated by subjects with MCI who developed AD over time. Interferon-gamma-inducible protein 10 is specifically increased in MCI and seems to decrease with the progression of AD, whereas MCP-1 and IL-8 are up-regulated also in late stages of the disease, suggesting a role in phases in which neurodegeneration is prevalent.     

Three-dimensional gray matter atrophy mapping in mild cognitive impairment and mild Alzheimer disease

BACKGROUND: Alzheimer disease (AD) is the most common form of dementia worldwide. Mild cognitive impairment (MCI) is the recent terminology for patients with cognitive deficiencies in the absence of functional decline. Most patients with MCI harbor the pathologic changes of AD and demonstrate transition to dementia at a rate of 10% to 15% per year. Patients with AD and MCI experience progressive brain atrophy. OBJECTIVE: To analyze the structural magnetic resonance imaging data for 24 patients with amnestic MCI and 25 patients with mild AD using an advanced 3-dimensional cortical mapping technique. DESIGN: Cross-sectional cohort design. Patients/ METHODS: We analyzed the structural magnetic resonance imaging data of 24 amnestic MCI (mean MMSE, 28.1; SD, 1.7) and 25 mild AD patients (all MMSE scores, >18; mean MMSE, 23.7; SD, 2.9) using an advanced 3-dimensional cortical mapping technique. RESULTS: We observed significantly greater cortical atrophy in patients with mild AD. The entorhinal cortex, right more than left lateral temporal cortex, right parietal cortex, and bilateral precuneus showed 15% more atrophy and the remainder of the cortex primarily exhibited 10% to 15% more atrophy in patients with mild AD than in patients with amnestic MCI. CONCLUSION: There are striking cortical differences between mild AD and the immediately preceding cognitive state of amnestic MCI. Cortical areas affected earlier in the disease process are more severely affected than those that are affected late. Our method may prove to be a reliable in vivo disease-tracking technique that can also be used for evaluating disease-modifying therapies in the future.