阿尔茨海默病血液生物学标志物研究现状

<正>阿尔茨海默病(AD)是老年中最常见的痴呆类型,我国的发病率为3%~7%,且随着年龄的增长,AD患病率逐渐升高。临床上AD分为痴呆前阶段和痴呆阶段;痴呆前阶段分为轻度认知功能障碍前期(pre-MCI)和轻度认知功能障碍期(MCI);痴呆阶段又可分为轻度、中度、重度。大量临床研究发现AD患者脑脊液β1-42淀粉样蛋白(Aβ1-42)水平升高,总Tau蛋白     

阿尔茨海默病相关血液学标志物研究进展

阿尔茨海默病(AD)是一种中枢神经系统退行性疾病,主要临床表现为记忆、认知障碍以及后期的人格和行为改变等。有很多血液学指标和AD密切相关,如蛋白质、基因突变、微小RNA(miRNA)等,或可用于预测AD发生风险、反映疾病阶段及支持AD诊断。血液学标志物的检测简便、易行,因此,筛选理想的AD相关血液学标志物有利于AD的筛查与治疗。文章总结了AD相关血液学标志物的研究现状,并讨论其应用于临床的可能性和局限性。     

脑脊液生物标志物在阿尔茨海默病诊断中的价值

阿尔茨海默病（AD）是一种老年期的神经退行性疾病,早期干预是目前延缓该病进展的唯一可靠手段。该文汇总并分析近年来各类AD生物标志物研究的代表性文献,分类评述了各类脑脊液（GSF）标志物对AD诊断及鉴别诊断的效能。其中CSF Aβ42、Aβ42/Aβ40、tau蛋白、Aβ42/p-tau、生长相关蛋白43、突触相关蛋白2...     

阿尔茨海默病的诊断进展

阿尔茨海默病（AD）是以进行性认知功能障碍和记忆损害为特征的神经退行性疾病,是老年人中常见的一种痴呆症口]。在进行性认知功能障碍的老年人中,AD病人占有50％～60％。随着世界人口的老龄化加剧,AD患者与日俱增,AD已经成为医学研究的一个热点。全世界可能有数千万的人正在遭受着AD的折磨,在美国,估计有450万名AD患者,中国AD患者人数也已超过500万,占全世界所有患病人数的1／4。故对AD的诊断特别是早期诊断特别重要,现就AD的诊断进展综述如下。     

血清碳酸酐酶III作为新型生物学标志物在阿尔茨海默病临床诊断中的应用价值

目的：探讨血清碳酸酐酶III（CAIII）在轻中度阿尔茨海默病（AD）临床诊断中的应用价值及其相关影响因素。方法：纳入106名初诊为轻中度AD的老年患者作为病例组（AD组）,同期89名正常老年人作为对照组。检测两组老年患者肝肾功能、血脂、血糖、叶酸和同型半胱氨酸等主要血清生化指标;通过简易精神状态检查量表（MMSE）评估认知水平;采用患者健康调查问卷9（PHQ-9）及广泛性焦虑量表（GAD-7）评估心理状况;利用改良巴氏指数（BI）评估受试者日常生活活动能力（ADL）;通过酶联免疫吸附试验测定血清CAIII水平。结果：AD组MMSE评分显著低于对照组（P＜0.05）,PHQ-9、GAD-7评分均明显高于对照组（均P＜0.05）,但两组受试者年龄、性别构成、受教育年限、ADL评分并无明显差异（均P＞0.05）。AD组血清CAIII水平较对照组明显下降（P＜0.05）,但不同性别、年龄、受教育年限及ADL评分AD患者之间的血清CAIII水平无明显统计学差异（均P＞0.05）。病程＞3年的AD患者血清CAIII水平低于病程≤3年患者（P＜0.05）。伴有抑郁或焦虑的AD患者血清CAIII水平明显低于情绪正常的AD患者（P＜0.05）,但不同程度抑郁或焦虑AD患者之间的血清CAIII水平并无明显差异（P＞0.05）。中度AD患者血清CAIII水平明显低于轻度AD患者（P＜0.05）。血肌酐（Scr）升高的AD患者血清CAIII水平明显高于Scr在正常范围内的AD患者（P＜0.05）。AD组患者血清CAIII水平与病程、PHQ-9评分及GAD-7评分之间呈负相关,与MMSE和Scr评分之间呈正相关（均P＜0.05）。PHQ-9得分、病情严重程度、Scr水平是轻中度AD老年患者血清CAIII水平的重要影响因素（均P＜0.05）。ROC曲线分析显示,血清CAIII诊断AD的敏感度和特异度分别为88.79%和96.74%。结论：血清CAIII可能成为轻中度AD老年患者诊断的新型生物学标志物之一,并有望成为AD的新型潜在干预靶点之一,但其内在分子机制仍待进一步探究。     

血清中DNA聚合酶α在阿尔茨海默病中的表达和诊断价值分析

目的 探究血清中DNA聚合酶α(DNA pol α)在阿尔茨海默病(AD)中的表达水平,分析其在AD中的诊断价值。方法 选取2019年3月至2023年4月在首都医科大学宣武医院就诊的AD痴呆(DAT)期患者100例作为DAT组,轻度认知障碍(MCI)期患者43例作为MCI组;同期,选取68例同年龄组别的健康者作为HC组。检测各组血清样本中DNA pol α的表达水平,利用受试者工作特征(ROC)曲线分析DNA pol α在AD中的诊断价值。结果 DAT组血清DNA pol α表达水平高于MCI组(P<0.05)和HC组(P<0.001),随着AD病程发展,DNA pol α表达水平有递增趋势。DNA pol α表达水平与简易智能精神状态检查量表(MMSE)和蒙特利尔认知评估量表(MoCA)评分均呈负相关(r=-0.155 3、-0.203 7,P<0.05)。DNA pol α诊断DAT期的曲线下面积(AUC)为0.682,灵敏度为0.900,特异度为0.412;DNA pol α诊断MCI期的AUC为0.546,灵敏度为0.977,特异度为0.250;DNA pol...     

阿尔茨海默病的临床诊断研究进展

阿尔茨海默病(Alzheimer’s disease,AD)是一种以痴呆为主要症状的进行性神经退行性疾病,主要发生于老年及老年前期,原因尚不明确。AD占所有痴呆的50%-60%,目前全世界约有1100万AD患者,据推测,到2025年这一数字将翻一番[1]。目前尚缺乏根本有效的治疗方法,特别是在疾病中晚期治     

阿尔茨海默病患者血浆鸟氨酸浓度与认知功能的相关性及其对认知功能下降的诊断价值

目的 探讨阿尔茨海默病（Alzheimer disease, AD）患者外周血鸟氨酸浓度的变化,分析其与简易精神状态检查（Mini-Mental State Examination, MMSE）量表的相关性以及对认知功能下降的诊断价值。方法 收集2020年10月至2022年1月就诊于复旦大学附属中山医院的26例经18F-AV45 PET确诊的AD患者（AD组）及30例社区同龄健康受试者（对照组）外周血样本,使用试剂盒对血浆鸟氨酸浓度进行测定。采用Pearson相关性分析评价血浆鸟氨酸浓度与MMSE评分的相关性;采用多元线性回归方程建立血浆鸟氨酸浓度、年龄、性别对MMSE评分影响的预测模型;采用受试者工作特征（receiver operating characteristic, ROC）曲线分析血浆鸟氨酸浓度对认知功能下降的诊断价值。结果 AD组平均血浆鸟氨酸浓度为（458.55±17.90）μmol/L,显著低于对照组[（640.21±36.48）μmol/L, P<0.001]。Pearson相关性分析显示血浆鸟氨酸浓度与MMSE评分正相关（r=0.437 9,P=0.000 ...     

阿尔茨海默病的诊断进展

阿尔茨海默病(AD)是老年期痴呆的最常见的原因,目前已有多个AD诊断标准,各标准之间存在差异,各有优劣.总结和比较各标准有助于临床医生及科研人员在不同情况下选择适合的标准用于诊断.随着AD诊断标准的演变,AD的病理生理学过程和生物学标志物的作用日益受到关注,对临床诊治和科学研究均具有重要意义.     

嗅觉脑功能成像检测嗅觉功能损害在阿尔茨海默病早期诊断中的作用

阿尔茨海默病(Alzheimer disease,AD)目前是一种较为常见、预后较差的慢性老年病,其临床表现为进行性的智能损害。全球约有3390万AD患者[1],65岁以上的AD患病率约为5%,年龄每增长5岁患病率增加约1.85倍,随着人口老龄化问题的加剧,在50年后AD的发病率可能提高3倍,患者可达1亿人,     

Impact of new diagnostic criteria for diabetes on different populations.

OBJECTIVE: For epidemiological purposes, it has now been recommended that a fasting plasma glucose value of 7.0 mmol/l can be used to diagnose diabetes, instead of a 2-h value of 11.1 mmol/l. This study assesses the impact of making this change on the prevalence of diabetes and on the phenotype of individuals identified. RESEARCH DESIGN AND METHODS: Data were collated from nine population based southern hemisphere studies in which a 75-g oral glucose tolerance test was performed. Comparisons were made between the prevalence derived from fasting values only and the prevalence derived from 2-h values only. Cardiovascular risk was assessed in all individuals. RESULTS: There were 20,624 subjects in the nine surveys of whom 1,036 had previously diagnosed diabetes and 1,714 had newly diagnosed diabetes, according to either fasting or 2-h glucose. The differences in prevalence within each population resulting from changing the diagnostic criteria ranged from +30 to -19% (relative difference) and +4.1 percentage points to -2.8 percentage points (absolute difference). BMI was the most important determinant of disagreement in classification. A total of 31% of those individuals who were diabetic on the fasting value were not diabetic on the 2-h value, and 32% of those with diabetes on the 2-h value were not diabetic on the fasting value. Apart from obesity, there were no differences in cardiovascular risk between those identified by the fasting and the 2-h values. CONCLUSIONS: Changing the diagnostic criteria is likely to have variable and sometimes quite large effects on the prevalence of diabetes in different populations. Furthermore, the fasting criterion identifies different people as being diabetic than those identified by the 2-h criterion.     

BMW diagnostic criteria for IBS

Rome I diagnostic criteria for IBS was published in 1992 and it became a global diagnostic criteria. However, the criteria was not practical and somewhat complicated. Moreover, its symptomatic duration was too long (defined as more than 3 months) to be introduced in clinical practice. Therefore, Japanese member of BMW(Bowel Motility Workshop) tried to develop a new diagnostic criteria for IBS and it was established in 1995 by way of the Delphi method. The criteria was named as BMW diagnostic criteria and it was shown below: BMW diagnostic criteria for IBS (1995) At least one month or more of repetitive symptoms of the following 1) and 2) and no evidence of organic disease that likely to explain the symptoms. 1) Existence of abdominal pain, abdominal discomfort or abdominal distension 2) Existence of abnormal bowel movement (diarrhea, constipation) Abnormal bowel movement includes at least one of the below; (1) Abnormal stool frequency (2) Abnormal stool form (lumpy/hard or loose/wartery stool) Moreover, the following test should be performed as a rule to exclude organic diseases. (1) Urinalysis, fecal occult blood testing, CBC, chemistry (2) Barium enema or colonofiberscopic examination The other diagnostic criteria for IBS was also reviewed and their characteristics were compared with BMW diagnostic criteria.     

Posttransplant thrombotic microangiopathy: sensitivity of proposed new diagnostic criteria

BACKGROUND: Objective diagnosis of transplantation-associated thrombotic microangiopathy (TA-TMA) has traditionally been difficult due to the multiple potential etiologies of thrombocytopenia and red blood cell fragmentation occurring after allogeneic hematopoietic stem cell transplantation (SCT). To attempt to address this issue of diagnostic uncertainty, two new diagnostic criteria for TA-TMA have recently been proposed: the Bone Marrow Transplant Clinical Trials Network (BMT-CTN) and the International Working Group (IWG) criteria. However, both newly proposed criteria are yet to be clinically validated.
STUDY DESIGN AND METHODS: All 15 cases of TA-TMA previously diagnosed at the authors' institution between December 2001 and March 2008 were retrospectively reclassified under the newly proposed BMT-CTN and IWG criteria.
RESULTS: Potential diagnostic pitfalls were identified in both the BMT-CTN and the IWG TA-TMA criteria. The main limitation of the BMT-CTN criteria appeared to be need for concurrent renal and/or neurologic dysfunction to be manifest at TA-TMA diagnosis, which was present in only 73% of our patient cohort. For the IWG criteria, the main limitation to TA-TMA diagnosis appeared to be the requirement for schistocytosis of more than 4%, which was present in only 27% of these patients.
CONCLUSION: Our experience suggests that potentially significant diagnostic pitfalls remain with both recently proposed TA-TMA diagnostic criteria, pitfalls that are likely to limit the diagnostic sensitivity of both. It is recommended that further clinical correlation of both the BMT-CTN and the IWG criteria be undertaken before either is routinely adapted into SCT practice.