主观认知衰退向轻度认知障碍或痴呆发展与阿尔茨海默病生物标志物的关系：一项荟萃分析。

Progression of Subjective Cognitive Decline to MCI or Dementia in Relation to Biomarkers for Alzheimer Disease: A Meta-analysis.

机构信息

From the Department of Psychiatry and Psychotherapy (A.R., L.B., C.B., F.J.), Faculty of Medicine and University Hospital, University of Cologne; Department of Neurodegeneration and Geriatric Psychiatry (M.W.), University Hospital Bonn; German Center for Neurodegenerative Diseases (DZNE) (M.W., F.J.), Venusberg Campus 1, Bonn; and Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (F.J.), University of Cologne, Germany.

出版信息

Neurology. 2022 Oct 25;99(17):e1866-e1874. doi: 10.1212/WNL.0000000000201072. Epub 2022 Aug 26.

DOI:10.1212/WNL.0000000000201072

PMID:36028322

Abstract

BACKGROUND AND OBJECTIVES

The risk of mild cognitive impairment (MCI) or dementia in individuals with subjective cognitive decline (SCD) and biomarkers indicating Alzheimer disease (AD) pathology in comparison with individuals with SCD without biomarker evidence for AD is critical to delineate the potential role of biomarker assessment in this group. We performed a meta-analysis of studies on this topic.

METHODS

Three databases (PubMed, PsycINFO, and Cochrane) were searched from inception to May 7, 2021. Search strings included the terms: subjective cognitive decline, biomarker, amyloid, tau, risk, Alzheimer, mild cognitive impairment, and dementia. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane guidelines, 2 researchers independently performed literature search, data collection, and data extraction. We summarized odds ratios (ORs) in random-effects meta-analyses and calculated sensitivity, specificity, positive predictive values (PPVs) and negative predictive values (NPVs), and likelihood ratios. The primary outcome was the OR of progression from SCD to MCI or dementia in cases with biomarkers indicative of AD pathology relative to the chance of progression in cases with biomarkers indicating no AD pathology.

RESULTS

Of 4,147 studies screened, 8 studies were selected. The risk of bias analysis revealed a low risk of bias in all studies. The prevalence of abnormal biomarkers ranged between 15.6% and 35.9% for amyloid, 11.1% and 33.6% for phosphorylated tau (p-tau), 12.3% and 46.3% for total tau (t-tau), and 7.8% and 24.4% for full AD pathology (amyloid pathology with either increased p-tau or t-tau). The chance of clinical progression was increased in cases of amyloid pathology only (OR 5.89, 95% CI 2.33-14.90), elevated p-tau (OR 3.99, 95% CI 2.34-6.85), elevated t-tau (OR 2.26, 95% CI 1.14-4.48), and full AD pathology (OR 11.36, 95% CI 1.97-65.41). The latter showed a PPV of 59.7% (95% CI 48.8%-69.3%) and an NPV of 89.4% (95% CI 86.7%-91.7%), whereas amyloid pathology only showed a PPV of 28.2% (95% CI 23.7%-32.2%) and an NPV of 94.9% (95% CI 93.4%-96.2%).

DISCUSSION

Individuals with SCD and full AD pathology have a substantially increased risk of developing MCI or dementia in comparison with individuals with SCD without AD pathology.

TRIAL REGISTRATION INFORMATION

PROSPERO CRD42020175282.

摘要

背景与目的

与无生物标志物证据表明存在 AD 病理的 SCD 患者相比，SCD 伴有轻度认知障碍（MCI）或痴呆风险以及提示阿尔茨海默病（AD）病理的生物标志物的个体，其潜在的生物标志物评估作用至关重要。我们对该主题的研究进行了荟萃分析。

方法

从成立到 2021 年 5 月 7 日，我们在三个数据库（PubMed、PsycINFO 和 Cochrane）中进行了搜索。搜索词包括：主观认知下降、生物标志物、淀粉样蛋白、tau、风险、阿尔茨海默病、MCI 和痴呆。根据系统评价和荟萃分析的首选报告项目以及 Cochrane 指南，两名研究人员独立进行了文献搜索、数据收集和数据提取。我们以随机效应荟萃分析总结了比值比（OR），并计算了敏感性、特异性、阳性预测值（PPV）和阴性预测值（NPV）以及似然比。主要结局是 AD 病理生物标志物阳性病例进展为 SCD 至 MCI 或痴呆的 OR，与 AD 病理生物标志物阴性病例进展的机会相比。

结果

在筛选出的 4147 项研究中，有 8 项研究入选。偏倚风险分析显示，所有研究的偏倚风险均较低。淀粉样蛋白异常生物标志物的患病率为 15.6%-35.9%，磷酸化 tau（p-tau）为 11.1%-33.6%，总 tau（t-tau）为 12.3%-46.3%，完整 AD 病理（淀粉样蛋白病理伴 p-tau 或 t-tau 升高）为 7.8%-24.4%。只有淀粉样蛋白病理（OR 5.89，95%CI 2.33-14.90）、p-tau 升高（OR 3.99，95%CI 2.34-6.85）、t-tau 升高（OR 2.26，95%CI 1.14-4.48）和完整 AD 病理（OR 11.36，95%CI 1.97-65.41）的病例发生临床进展的可能性增加。后者的 PPV 为 59.7%（95%CI 48.8%-69.3%），NPV 为 89.4%（95%CI 86.7%-91.7%），而淀粉样蛋白病理的 PPV 仅为 28.2%（95%CI 23.7%-32.2%），NPV 为 94.9%（95%CI 93.4%-96.2%）。