MRC London Institute of Medical Sciences, Imperial College London, London, UK.
Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
Cochrane Database Syst Rev. 2021 Feb 10;2(2):CD010945. doi: 10.1002/14651858.CD010945.pub2.
Dementia is a syndrome that comprises many differing pathologies, including Alzheimer's disease dementia (ADD), vascular dementia (VaD) and frontotemporal dementia (FTD). People may benefit from knowing the type of dementia they live with, as this could inform prognosis and may allow for tailored treatment. Beta-amyloid (1-42) (ABeta42) is a protein which decreases in both the plasma and cerebrospinal fluid (CSF) of people living with ADD, when compared to people with no dementia. However, it is not clear if changes in ABeta42 are specific to ADD or if they are also seen in other types of dementia. It is possible that ABeta42 could help differentiate ADD from other dementia subtypes.
To determine the accuracy of plasma and CSF ABeta42 for distinguishing ADD from other dementia subtypes in people who meet the criteria for a dementia syndrome.
We searched MEDLINE, and nine other databases up to 18 February 2020. We checked reference lists of any relevant systematic reviews to identify additional studies.
We considered cross-sectional studies that differentiated people with ADD from other dementia subtypes. Eligible studies required measurement of participant plasma or CSF ABeta42 levels and clinical assessment for dementia subtype.
Seven review authors working independently screened the titles and abstracts generated by the searches. We collected data on study characteristics and test accuracy. We used the second version of the 'Quality Assessment of Diagnostic Accuracy Studies' (QUADAS-2) tool to assess internal and external validity of results. We extracted data into 2 x 2 tables, cross-tabulating index test results (ABeta42) with the reference standard (diagnostic criteria for each dementia subtype). We performed meta-analyses using bivariate, random-effects models. We calculated pooled estimates of sensitivity, specificity, positive predictive values, positive and negative likelihood ratios, and corresponding 95% confidence intervals (CIs). In the primary analysis, we assessed accuracy of plasma or CSF ABeta42 for distinguishing ADD from other mixed dementia types (non-ADD). We then assessed accuracy of ABeta42 for differentiating ADD from specific dementia types: VaD, FTD, dementia with Lewy bodies (DLB), alcohol-related cognitive disorder (ARCD), Creutzfeldt-Jakob disease (CJD) and normal pressure hydrocephalus (NPH). To determine test-positive cases, we used the ABeta42 thresholds employed in the respective primary studies. We then performed sensitivity analyses restricted to those studies that used common thresholds for ABeta42.
We identified 39 studies (5000 participants) that used CSF ABeta42 levels to differentiate ADD from other subtypes of dementia. No studies of plasma ABeta42 met the inclusion criteria. No studies were rated as low risk of bias across all QUADAS-2 domains. High risk of bias was found predominantly in the domains of patient selection (28 studies) and index test (25 studies). The pooled estimates for differentiating ADD from other dementia subtypes were as follows: ADD from non-ADD: sensitivity 79% (95% CI 0.73 to 0.85), specificity 60% (95% CI 0.52 to 0.67), 13 studies, 1704 participants, 880 participants with ADD; ADD from VaD: sensitivity 79% (95% CI 0.75 to 0.83), specificity 69% (95% CI 0.55 to 0.81), 11 studies, 1151 participants, 941 participants with ADD; ADD from FTD: sensitivity 85% (95% CI 0.79 to 0.89), specificity 72% (95% CI 0.55 to 0.84), 17 studies, 1948 participants, 1371 participants with ADD; ADD from DLB: sensitivity 76% (95% CI 0.69 to 0.82), specificity 67% (95% CI 0.52 to 0.79), nine studies, 1929 participants, 1521 participants with ADD. Across all dementia subtypes, sensitivity was greater than specificity, and the balance of sensitivity and specificity was dependent on the threshold used to define test positivity.
AUTHORS' CONCLUSIONS: Our review indicates that measuring ABeta42 levels in CSF may help differentiate ADD from other dementia subtypes, but the test is imperfect and tends to misdiagnose those with non-ADD as having ADD. We would caution against the use of CSF ABeta42 alone for dementia classification. However, ABeta42 may have value as an adjunct to a full clinical assessment, to aid dementia diagnosis.
痴呆是一种包含多种不同病理的综合征，包括阿尔茨海默病性痴呆（ADD）、血管性痴呆（VaD）和额颞叶痴呆（FTD）。如果人们知道自己患有哪种类型的痴呆，可能会对预后有所了解，并且可能会得到针对性的治疗。β-淀粉样蛋白（1-42）（ABeta42）在患有 ADD 的人群的血浆和脑脊液（CSF）中均会减少，而在无痴呆的人群中则不会。然而，目前尚不清楚 ABeta42 的变化是否仅存在于 ADD 中，或者是否也存在于其他类型的痴呆中。ABeta42 可能有助于将 ADD 与其他痴呆亚型区分开来。
确定血浆和 CSF ABeta42 对符合痴呆综合征标准的人群中区分 ADD 与其他痴呆亚型的准确性。
我们检索了 MEDLINE 以及其他九个数据库，检索时间截至 2020 年 2 月 18 日。我们检查了任何相关系统评价的参考文献列表，以确定其他研究。
我们考虑了将患有 ADD 的人群与其他痴呆亚型区分开来的横断面研究。合格的研究需要测量参与者的血浆或 CSF ABeta42 水平，并对痴呆亚型进行临床评估。
七位独立工作的综述作者筛选了搜索生成的标题和摘要。我们收集了关于研究特征和测试准确性的数据。我们使用“诊断准确性研究的质量评估工具”（QUADAS-2）的第二版来评估结果的内部和外部有效性。我们将数据提取到 2x2 表中，交叉列出了索引测试结果（ABeta42）与参考标准（每种痴呆亚型的诊断标准）。我们使用双变量、随机效应模型进行了荟萃分析。我们计算了敏感性、特异性、阳性预测值、阳性和阴性似然比及其相应的 95%置信区间（CI）的汇总估计值。在主要分析中，我们评估了血浆或 CSF ABeta42 对区分 ADD 与其他混合性痴呆类型（非 ADD）的准确性。然后，我们评估了 ABeta42 对区分 ADD 与特定痴呆类型的准确性：VaD、FTD、路易体痴呆（DLB）、酒精相关认知障碍（ARCD）、克雅氏病（CJD）和正常压力脑积水（NPH）。为了确定阳性测试结果，我们使用了各自研究中使用的 ABeta42 阈值。然后，我们进行了敏感性分析，仅包括使用 ABeta42 常见阈值的研究。
我们确定了 39 项研究（5000 名参与者），这些研究使用 CSF ABeta42 水平来区分 ADD 与其他类型的痴呆。没有研究使用血浆 ABeta42 符合纳入标准。没有研究在 QUADAS-2 的所有领域都被评为低偏倚风险。高偏倚风险主要存在于患者选择（28 项研究）和索引测试（25 项研究）领域。区分 ADD 与其他痴呆亚型的汇总估计值如下：ADD 与非 ADD：敏感性 79%（95%CI 0.73 至 0.85），特异性 60%（95%CI 0.52 至 0.67），13 项研究，1704 名参与者，880 名患有 ADD；ADD 与 VaD：敏感性 79%（95%CI 0.75 至 0.83），特异性 69%（95%CI 0.55 至 0.81），11 项研究，1151 名参与者，941 名患有 ADD；ADD 与 FTD：敏感性 85%（95%CI 0.79 至 0.89），特异性 72%（95%CI 0.55 至 0.84），17 项研究，1948 名参与者，1371 名患有 ADD；ADD 与 DLB：敏感性 76%（95%CI 0.69 至 0.82），特异性 67%（95%CI 0.52 至 0.79），9 项研究，1929 名参与者，1521 名患有 ADD。在所有痴呆亚型中，敏感性均大于特异性，敏感性和特异性的平衡取决于用于定义阳性测试的阈值。
我们的综述表明，测量 CSF 中的 ABeta42 水平可能有助于区分 ADD 与其他痴呆亚型，但该测试并不完美，并且往往会错误地将非 ADD 患者诊断为 ADD。我们建议不要单独使用 CSF ABeta42 进行痴呆分类。然而，ABeta42 可能作为完整临床评估的辅助手段，有助于痴呆诊断。
