血清BDNF与尿AD7c-NTP联合检测在MCI进展为AD中的预测价值

目的探讨血清BDNF与尿AD7c-NTP联合检测对轻度认知功能障碍(MCI)进展为阿尔茨海默病的预测价值。方法收集172例MCI患者(MCI组)及90例健康者(正常对照组)基线、12 m、24 m的血清BDNF和尿AD7c-NTP的表达水平。结果 MCI患者血清BDNF水平在基线、12 m、24 m显著低于同期对照组(P0.05),而尿AD7c-NTP水平在基线、12 m、24 m显著高于同期对照组(P0.01)。此外,32例MCI患者于随访的2y中进展为AD(MCI-AD组),其血清BDNF水平在基线、12 m、24 m显著低于稳定型MCI患者(MCI-ST组),而尿AD7c-NTP水平在基线、12 m、24 m显著高于稳定型MCI患者。结论血清BDNF与尿AD7c-NTP联合检测是鉴别及诊断MCI进展为AD的较好指标,提升二者单独应用时的预测价值。     

尿AD7c-NTP水平与载脂蛋白E ε4等位基因联合检测对轻度认知功能障碍的诊断价值

目的探讨尿AD7c-NTP水平与载脂蛋白Eε4等位基因(ApoEε4)联合检测在轻度认知功能障碍(MCI)的诊断价值。方法检测54例MCI患者(MCI组)及60例健康者(正常对照组)的尿AD7c-NTP水平和ApoEε4表达。结果 MCI组尿AD7c-NTP水平及阳性率显著高于正常对照组(均P0.01)。MCI组ApoEε4阳性率显著高于对照组(P0.05)。联合检测的灵敏度、特异度、阳性预测值、阴性预测值及约登指数均高于尿AD7c-NTP检测和ApoEε4检测。结论尿AD7c-NTP水平与ApoEε4联合检测是鉴别及诊断MCI早期病变的较好指标,提升二者单独应用时的预测价值。     

尿AD7c-NTP、血浆Hcy与老年性痴呆患者关系的研究

目的研究尿AD7c-NTP和血浆Hcy与老年性痴呆患者(AD)的关系。方法筛选轻度AD患者67例、中重度AD患者53例、健康老年人120例,分别采用双抗体夹心法(ELISA法)和循环酶法检测患者尿液AD7c-NTP和血浆Hcy的含量。结果 3组尿AD7c-NTP含量差异具有统计学意义(P<0.05),且轻度AD组和中重度AD组比较、轻度AD组和健康对照组比较,差异均具有统计学意义(P<0.05);轻度AD组和中重度AD组尿AD7c-NTP含量与MMSE呈负相关。根据ROC曲线,确定尿AD7c-NTP的值大于1.75ng/ml为诊断AD的切点。3组血浆Hcy含量差异具有统计学意义(P<0.05),且轻度AD组和健康对照组比较,差异具有统计学意义(P<0.05),但轻度AD组和中重度AD组比较差异不具有统计学意义(P>0.05);轻度AD组和中重度AD组血浆Hcy含量与MMSE无明显相关性。根据ROC曲线,确定血浆Hcy的值大15.55μmol/L作为诊断AD的切点。结论尿AD7c-NTP和血浆Hcy与老年性痴呆密切相关,临床中可将二者联合的检测结果用作诊断AD的辅助指标。     

尿液AD7c-NTP检测在阿尔茨海默病早期诊断中的价值

目的 探讨尿液阿尔茨海默病(AD)相关神经丝蛋白(AD7c-NTP)表达水平在AD及遗忘型轻度认知障碍(aMCI)中的诊断价值.方法 采用酶联免疫吸附试验检测尿液AD7c-NTP表达水平,比较54例AD组、68例aMCI组及46例对照组患者的尿液AD7c-NTP表达水平的差异,并分析尿液AD7c-NTP检测在AD及aM...     

不同类型认知障碍患者的尿液AD7c-NTP与头部MRI、MRS的相关性研究

目的研究对不同类型认知障碍患者的尿液AD相关神经丝蛋白(AD7c-NTP)水平与头颅MRI中海马萎缩程度、MRS中N-乙酰天门冬氨酸(NAA)峰值水平的相互关系。方法选取阿尔兹海默病(AD)、血管性痴呆(VD)、轻度认知障碍(MCI)患者各30例,分别设为AD组、VD组、MCI组,另选取同期体检健康者30例作对照组。取所有受检者晨起时尿液,以酶联免疫吸附法测定AD7c-NTP水平,行头颅MRI及MRS检查。对比四组尿液AD7c-NTP水平、海马萎缩MTA评分、NAA峰值水平,分析尿液AD7c-NTP与海马萎缩MTA评分、NAA峰值水平相关性。结果 MCI组尿液AD7c-NTP水平高于对照组,VD组尿液AD7c-NTP水平高于MCI组,AD组尿液AD7c-NTP水平高于Va D组,差异有统计学意义(P0.05);MCI组海马萎缩MTA评分与对照组比较,差异无统计学意义(P0.05),VD组海马萎缩MTA评分高于MCI组,AD组海马萎缩MTA评分高于VD组,差异有统计学意义(P0.05);MCI组NAA峰值水平与对照组比较,差异无统计学意义(P0.05),VD组NAA峰值水平低于MCI组,AD组NAA峰值水平低于VD组,差异有统计学意义(P0.05);尿液AD7c-NTP水平变化与海马萎缩MTA评分呈正相关关系(P0.05);与NAA峰值水平呈负相关关系(P0.05)。结论 AD、Va D、MCI患者尿液AD7c-NTP水平较高,且不同类型认知障碍患者尿液AD7c-NTP、海马萎缩MTA评分、NAA峰值水平存在明显差异,尿液AD7c-NTP水平变化与MRI改变呈正相关性,与MRS改变呈负相关性。     

老年阿尔茨海默病患者尿液中神经丝蛋白含量的研究

目的探讨尿液中阿尔茨海默病(AD)相关神经丝蛋白(AD7c-NTP)含量在老年AD诊断中的意义。方法选择老年AD患者67例(AD组)和认知功能正常老年人(对照组)85名,应用简易精神状态检查(MMSE)量表、日常生活活动(ADL)量表和临床痴呆评定(CDR)量表进行精神状态评价,采用酶联免疫吸附测定(ELISA)法检测尿AD7c-NTP含量。结果尿AD7c-NTP含量AD组为(2.34±1.59)μg·L-1,对照组为(1.04±0.39)μg·L-1,两组间差异有统计学意义(t=-6.59,P=0.000)。经相关性分析表明AD7c-NTP水平与MMSE、FT4值呈负相关(R=-0.689,P=0.000;R=-0.211,P=0.009);与ADL、CDR值呈正相关(R=0.267,P=0.001;R=0.52,P=0.001)。根据ROC曲线,确定1.492μg·L-1为界定值,其对应的敏感度和特异度分别为82.1%和95.3%,ROC曲线下面积为0.924,95%CI:0.88~0.97。结论尿AD7c-NTP含量检测可作为老年AD患者辅助诊断的生物学指标。     

阿尔茨海默病患者血清脑源性神经营养因子水平的改变及意义

目的研究阿尔茨海默病(AD)患者血清脑源性神经营养因子(BDNF)水平的改变及意义。方法对40例AD患者(AD组)用酶联免疫吸附法检测血清BDNF水平、聚合酶链反应-限制性片段长度多态性对APOE基因进行分型及神经心理评估,并与遗忘型轻度认知障碍(a MCI组)患者和正常对照者(正常对照组)进行比较,分析AD患者血清BDNF水平及与临床指标的相关性。结果与正常对照组相比,AD和a MCI血清BDNF水平差异无统计学意义(F=1.21,P=0.33);a MCI、轻度AD、中重度AD组间BDNF水平差异无统计学意义(F=2.31,P=0.08);相关分析发现是否携带APOEε4等位基因和简易精神状态检查(MMSE)评分不能影响血清BDNF水平(P>0.05)。结论血清BDNF水平既不能作为AD早期诊断的外周标志物,也不能反映AD病情的严重程度。     

阿尔茨海默病患者尿中AD7c-NTP含量的研究

目的探讨尿中阿尔茨海默病相关神经丝蛋白(AD7c-NTP)含量在阿尔茨海默病(AD)诊断中的意义。方法采用直接竞争性酶联免疫吸附测定法(ELISA),检测218例老年人,其中AD组46例、血管性痴呆组(VD组)50例、智能正常老年对照组122例尿液中AD7c-NTP含量,所有数据均经过SPSS软件进行统计学处理。结果AD组、VD组及智能正常老年对照组尿液中AD7c-NTP含量分别为33.35±1.61、18.19±1.41、18.30±1.45μg/ml,AD组明显高于其他两组,而VD组与智能正常老年对照组差异无统计学意义(P>0.05);91.4%的AD病例AD7c-NTP含量升高((22μg/ml),非AD病例中90.7%均为正常(?22μg/ml)。结论尿液中AD7c-NTP含量检测作为无创性检查,在AD诊断中具有重要的临床参考价值。     

APOE ε4等位基因与尿AD7c-NTP联合检测在AD早期诊断中的初步研究

目的探讨APOEε4等位基因与尿AD7c-NTP联合检测在阿尔兹海默病(AD)早期诊断预防中的价值。方法根据中国精神障碍分类与诊断标准第三版(CCMD-3)有关精神分裂症及轻度阿尔兹海默病的诊断标准,选取76例临床诊断疑似AD患者(PAD组),另选90例健康者作为对照组。对比两组APOEε4等位基因频率和尿AD7c-NTP含量对AD的诊断价值。结果 (1)APOEε4等位基因表达频率在PAD组显著高于对照组(P≤0.05);(2)尿AD7c-NTP在PAD组中的含量较对照组显著升高(P≤0.01);(3)对APOEε4、AD7c-NTP及二者联合检测进行比较发现,APOEε4对AD诊断的灵敏度、特异度、阳性预测值、阴性预测值、约登指数分别为:44.64%、88.33%、78.13%、63.10%、0.33;尿AD7c-NTP诊断的灵敏度、特异度、阳性预测值、阴性预测值、约登指数分别为:78.57%、83.33%、81.48、80.65%、0.62;APOEε4与AD7c-NTP联合检测的诊断灵敏度、特异度、阳性预测值、阴性预测值、约登指数分别为:91.18%、91.55%、83.78%、95.58%、0.82。结论 APOEε4等位基因与尿AD7c-NTP联合检测是监测及诊断AD早期病变的较好指标,提升二者单独应用时的预测价值,宜作为AD易发人群鉴别和早期诊断的生物标记物。     

尿阿尔茨海默病相关神经丝蛋白联合血浆同型半胱氨酸测定在阿尔茨海默病诊断中的研究

目的 探讨尿阿尔茨海默病（AD）相关神经丝蛋白（AD7c-NTP）含量测定联合血浆同型半胱氨酸（Hcy）在AD诊断中的价值。方法 纳入轻度阿尔茨海默病（CDR=1分）及中重度阿尔茨海默病患（CDR ≥ 2分）者各40例,并选择健康体检志愿者40例为对照组,采用酶联免疫吸附测定法（ELISA）检测尿液中AD7c-NTP含量,采用循环酶法测定血浆Hcy的含量,通过绘制ROC曲线,分析二者联合检测对AD的诊断准确性。结果 3组受试者尿AD7c-NTP含量比较,差异有统计学意义（P<0.05）;组间比较差异均有统计学意义（P<0.05）。根据ROC曲线,当尿AD7c-NTP为1.745 ng/mL时,对应的灵敏度和特异度之和最大。3组受试者血浆Hcy的含量比较,差异有统计学意义（P<0.05）;组间比较差异均有统计学意义（P<0.01）。根据ROC曲线,当血浆HCY为15.05 μmol/L时,对应的灵敏度和特异度之和最大。当二者进行联合检测时,ROC曲线下面积为0.891,大于各项单独检测。结论 AD患者尿AD7c-NTP含量及血浆HCY含量均增高;尿液AD7c-NTP含量及血浆HCY含量可作为辅助AD诊断的生物标记物;二者联合检测可提高AD诊断的准确性。     

MCI患者血清中Tau蛋白 Aβ1-42P-tau的检测价值分析

目的 探讨血清磷酸化Tau（P-tau）、β淀粉样蛋白1-42（Aβ1-42）以及Tau蛋白在轻度认知障碍（MCI）患者中的临床应用价值.方法 采用酶联免疫法测定主诉健忘组（SMC）30例,MCI患者30例,阿尔茨海默病组（AD）68例（轻度AD 24例,中度AD 22例,重度AD 22例）以及健康对照组35例血清中P-tau、Aβ1-42、Tau蛋白水平,并分析三种标记物与疾病的相关性.结果 与对照组及MCI组相比,MCI组、AD组MMSE评分显著上升,差异有统计学意义（P〈0.05）,重度AD组MMSE评分显著高于轻度、中度AD组,两两比较差异有统计学意义（P〈0.05）.与对照组相比,MCI组、AD组P-tau、Tau蛋白水平显著上升,且AD组高于MCI组,而Aβ1-42水平显著下降,且AD组下降幅度大于MCI组,差异有统计学意义（P〈0.05）.其中重度AD组P-tau、Tau蛋白水平高于轻度、中度AD组,而Aβ1-42水平低于轻、中度组,差异有统计学意义（P〈0.05）.SMC 组与对照组相比,各标记物水平差异无统计学意义（P〉0.05）.与单纯Tau蛋白、Aβ1-42、P-tau诊断相比,Tau蛋白、Aβ1-42、P-tau联合诊断的灵敏性、特异性、准确性显著增加,差异有统计学意义（P〈0.05）.结论 MCI病情发生及发展过程可能与血清P-tau、Aβ1-42、Tau蛋白水平异常有关,通过测定这三种标记物可有效预测MCI患者病情进展情况.     

Anosognosia in very mild Alzheimer's disease but not in mild cognitive impairment

OBJECTIVE: To study awareness of cognitive dysfunction in patients with very mild Alzheimer's disease (AD) and subjects with mild cognitive impairment (MCI). METHODS: A complaint interview covering 13 cognitive domains was administered to 82 AD and 79 MCI patients and their caregivers. The patient groups were comparable according to age and education, and Mini Mental State Examination (MMSE) scores were > or =24 in all cases. The discrepancy between the patients' and caregivers' estimations of impairments was taken as a measure of anosognosia. RESULTS: Self-reports of cognitive difficulties were comparable for AD and MCI patients. However, while in comparison to caregivers MCI patients reported significantly more cognitive impairment (p < 0.05), AD patients complained significantly less cognitive dysfunctions (p < 0.001). CONCLUSIONS: While most MCI patients tend to overestimate cognitive deficits when compared to their caregiver's assessment, AD patients in early stages of disease underestimate cognitive dysfunctions. Anosognosia can thus be regarded as a characteristic symptom at a stage of very mild AD (MMSE > or =24) but not MCI. Accordingly, medical history even in mildly affected patients should always include information from both patient and caregiver.     

Efficacy of rivastigmine in subjects with moderately severe Alzheimer's disease

BACKGROUND: Cholinesterase (ChE) inhibitors are primarily used in the treatment of mild to moderate Alzheimer's disease (AD), but may also be effective in more severe disease. OBJECTIVE: To evaluate the dual ChE inhibitor, rivastigmine, in more severe dementia. METHODS: We retrospectively analysed pooled data from three randomised, placebo-controlled, double-blind, 6-month trials, involving 2126 AD subjects. Subjects were selected according to baseline Mini-Mental State Examination (MMSE) score to identify subjects with more severe cognitive impairment (10-12 MMSE points). One-hundred-and-seventeen subjects were included who had been treated with rivastigmine 6-12 mg/day or placebo. The AD Assessment Scale-Cognitive Subscale (ADAS-Cog), the MMSE, a six-item subscore of the Progressive Deterioration Scale (PDS) and the BEHAVE-AD assessed efficacy. Tolerability was assessed by recording adverse events (AEs) and the relative risk (RR) of discontinuation. RESULTS: This group of subjects responded well to rivastigmine. After 6 months, the mean ADAS-Cog score declined by 6.3 points in the placebo group and increased by 0.2 points in the rivastigmine group (observed cases; p<0.001). Clinical benefits were also observed with the MMSE, the six-item PDS score and items of the BEHAVE-AD. Rivastigmine showed the same pattern of AEs as in other studies, but the RR of dropping out due to AEs was lower than in subjects with milder AD. CONCLUSION: Current treatment guidelines do not recommend treating individuals with severe AD with ChE inhibitors. However, this retrospective analysis suggests that rivastigmine 6-12 mg/day may benefit subjects with more severe disease, as well as subjects with mild to moderate impairment.     

The AD7c-NTP neuronal thread protein biomarker for detecting Alzheimer's disease

Dementia in Alzheimer's disease (AD) is ultimately due to cell loss mediated by several mechanisms including, apoptosis, impaired mitochondrial function, and possibly necrosis. A second major neuroanatomic correlate of dementia is aberrant cortical neuritic sprouting with abundant proliferation of dystrophic neurites. Early in vivo detection of AD will require non-invasive assays of highly sensitive and relatively specific biomarkers that reflect these fundamental abnormalities in cellular function. The AD-associated neuronal thread protein (AD7c-NTP) gene encodes a approximately 41 kD membrane-spanning phosphoprotein that causes apoptosis and neuritic sprouting in transfected neuronal cells. The AD7c-NTP gene is over-expressed in AD beginning early in the course of disease. In the brain, increased AD7c-NTP immunoreactivity is associated with phospho-tau-immunoreactive cytoskeletal lesions, but not with amyloid-beta accumulations. The levels of AD7c-NTP in postmortem brain tissue correlate with the levels measured in paired ventricular fluid samples, suggesting that the protein is secreted or released by dying cells into cerebrospinal fluid (CSF). In this regard, elevated levels of AD7c-NTP can be detected in both CSF and urine of patients with early or moderately severe AD, and the CSF and urinary levels of AD7c-NTP correlate with the severity of dementia. The newest configuration of the AD7c-NTP assay, termed "7c Gold", has greater than 90% aggregate results from a number of studies suggest that AD7c-NTP is an excellent biomarker that could be helpful in the routine clinical evaluation of elderly patients at risk for AD.     

Alzheimer氏病患者的日常生活能力及其相关因素分析

目的 了解Ａｌｚｈｅｉｍｅｒ氏病（ＡＤ）患者的日常生活能力及其相关因素。方法 对６０例ＡＤ患者（轻度２３例、中度２３例、重度１４例）和２０例非痴呆老人进行日常生活能力量表评定,同时对ＡＤ患者进行了日常生活能力相关因素的调查。结果 与非痴呆老人相比较,轻度ＡＤ患者主要表现为工具性日常生活能力（ＬＡＤＬ）减退,中度ＡＤ患者出现明显的躯体生活自理能力（ＰＳＭ）的减退,重度ＡＤ患者ＬＡＤＬ和ＰＳＭ均严重减     

Cholinergic plasticity in hippocampus of individuals with mild cognitive impairment: correlation with Alzheimer's neuropathology

Several recent studies indicate that activity of cholinergic enzymes in the cortex of people with mild cognitive impairment (MCI) and early Alzheimer's disease (AD) are preserved. We correlated levels of hippocampal choline acetyltransferase (ChAT) activity with the extent of AD lesions in subjects from the Religious Order Study, including cases with no cognitive impairment (NCI), MCI, and with mild to moderate AD. Hippocampal ChAT activity levels were also determined in a group of end-stage AD patients who were enrolled in the University of Pittsburgh Alzheimer's Disease Research Center. MCI subjects were characterized with increased hippocampal ChAT activity. This elevation was no longer present in mild AD cases, which were not different from NCI subjects. Severe AD cases showed markedly depleted hippocampal ChAT levels. In NCI, MCI, and mild-moderate AD, there was a positive correlation between hippocampal ChAT activity levels and progression of neuritic plaque pathology in entorhinal cortex and hippocampus. A significant elevation of hippocampal ChAT in the MCI group was found selectively in the limbic (i.e., entorhinal-hippocampal, III/IV) Braak stages. We hypothesize that cholinergic changes in the hippocampus of MCI subjects reflect a compensatory response to the progressive denervation of the hippocampus by lost entorhinal cortex input. Moreover, the present findings suggest that the short-term memory loss observed in MCI is not caused by cholinergic deficits; it more likely relates to disrupted entorhinal-hippocampal connectivity.     

A preliminary study of the Six-Item Screener in detecting cognitive impairment

Objective

The present retrospective study was to explore the clinical value of Six-Item Screener (SIS), which is constituted by 6 items from mini-mental status examination (MMSE), to identify cognitive impairment.

Methods

A total number of 1976 patients aged over 50 years, from the Memory Clinic of Huashan Hospital were employed in a battery of neuropsychological tests including MMSE. Subjects with severe conditions, unable to cooperate, or having been previously enrolled, were excluded from this study. The employed subjects were divided into 3 groups: subjective memory complaints (SMCs) (475 cases), patients with mild cognitive impairment (MCI) (440 cases), and patients with Alzheimer’s disease (AD) (1061 cases, including 555 mild, 339 moderate, and 167 severe). A total score of MMSE and a score of SIS composed of date, month, year, three-word delayed recall from MMSE were calculated. Data were analyzed based on educational background.

Results

The cut-off of SIS score was ⩽ 2 for illiterate, ⩽ 3 for elementary, and ⩽ 4 for junior high school or above. The sensitivity and specificity of SIS for detecting mild AD were 88.5% and 78.3%, respectively, with an overall accuracy of 83.8%, while for detecting MCI, the sensitivity and specificity were 34.3% and 90.1%, respectively, with an overall accuracy of 63.2%.

Conclusion

SIS is an effective and reliable instrument for dementia detection in outpatient department. However, it has limited value for MCI identification.