高同型半胱氨酸血症与认知结局风险：前瞻性队列研究的更新剂量-反应荟萃分析。

Hyperhomocysteinemia and risk of incident cognitive outcomes: An updated dose-response meta-analysis of prospective cohort studies.

机构信息

College of Medicine & Health, Lishui University, Lishui City, Zhejiang Province, 323000, China.

出版信息

Ageing Res Rev. 2019 May;51:55-66. doi: 10.1016/j.arr.2019.02.006. Epub 2019 Feb 28.

DOI:10.1016/j.arr.2019.02.006

PMID:30826501

Abstract

OBJECTIVE

This study aimed to comprehensively assess the dose-response relationship between blood homocysteine levels and risk of all cause, Alzheimer and vascular dementia, as well as cognitive impairment without dementia (CIND).

METHOD

We searched for all related prospective cohort studies reporting homocysteine as an exposure from patients with cognitive disorders as a result in the PubMed and EMBASE databases up to June 18, 2018. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) were extracted. The dose-response meta-analyses were conducted to assess potential linear and non-linear dose-response relations. Summary RRs and 95% CIs were calculated using a random- or fixed-effects model.

RESULTS

Twenty-eight prospective cohort studies were eligible in this meta-analysis. During average follow-up periods ranging from 2.7 to 35 years there were 2557 cases (1035 all-cause dementia, 530 Alzheimer's disease, 92 vascular dementia and > 900 CIND) among 28,257 participants. There was a clear linear dose-response relationship between blood homocysteine concentration and risk of Alzheimer-type dementia (P > 0.05 for non-linearity). The pooled RR of Alzheimer-type dementia was 1.15 (95% CI: 1.04 to 1.26; I = 56.6%, n = 5) for every 5 μmol/L increase in blood homocysteine. Sensitivity analysis showed similar results, and there was no clear evidence of publication bias with Begg's and Egger's tests for Alzheimer dementia (P = 0.806, 0.084, respectively), strengthening the linear relationship between blood homocysteine levels and risk of Alzheimer dementia. Due to the presence of publication bias and low statistical power, elevated levels of blood homocysteine were not appreciably associated with risk of all-cause, vascular dementia and CIND.

CONCLUSIONS

Every 5 μmol/L increase in blood homocysteine is linearly associated with a 15% increase in relative risk of Alzheimer-type dementia. This meta-analysis provides further evidence that a higher concentration of blood homocysteine is associated with a higher risk of Alzheimer-type dementia.

摘要

目的

本研究旨在全面评估血液同型半胱氨酸水平与全因、阿尔茨海默病和血管性痴呆以及无痴呆认知障碍（CIND）风险之间的剂量-反应关系。

方法

我们在 PubMed 和 EMBASE 数据库中检索了截至 2018 年 6 月 18 日所有与认知障碍患者血液同型半胱氨酸暴露结果相关的前瞻性队列研究。提取了汇总相对风险（RR）和相应的 95%置信区间（CI）。采用随机或固定效应模型进行剂量-反应荟萃分析，以评估潜在的线性和非线性剂量-反应关系。使用随机或固定效应模型计算汇总 RR 和 95%CI。

结果

本荟萃分析纳入了 28 项前瞻性队列研究。在平均 2.7 至 35 年的随访期间，28257 名参与者中有 2557 例（1035 例全因痴呆、530 例阿尔茨海默病、92 例血管性痴呆和>900 例 CIND）。血液同型半胱氨酸浓度与阿尔茨海默病型痴呆风险之间存在明确的线性剂量-反应关系（非线性检验 P>0.05）。每增加 5μmol/L 血液同型半胱氨酸，阿尔茨海默病型痴呆的汇总 RR 为 1.15（95%CI：1.04 至 1.26；I=56.6%，n=5）。敏感性分析得到了相似的结果，Begg 和 Egger 检验均未发现阿尔茨海默病发表偏倚的明确证据（P=0.806，0.084），这加强了血液同型半胱氨酸水平与阿尔茨海默病风险之间的线性关系。由于存在发表偏倚和低统计效能，血液同型半胱氨酸水平升高与全因、血管性痴呆和 CIND 的风险无明显关联。