生殖因素与痴呆症的关联：观察性研究的系统评价和剂量反应荟萃分析

Association of reproductive factors with dementia: A systematic review and dose-response meta-analyses of observational studies.

作者信息

Fu Chunying, Hao Wenting, Shrestha Nipun, Virani Salim S, Mishra Shiva Raj, Zhu Dongshan

机构信息

Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.

NHC Key Lab of Health Economics and Policy Research (Shandong University), Jinan, 250012, China.

出版信息

EClinicalMedicine. 2021 Dec 14;43:101236. doi: 10.1016/j.eclinm.2021.101236. eCollection 2022 Jan.

DOI:10.1016/j.eclinm.2021.101236

PMID:34977513

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8683685/

Abstract

BACKGROUND

Associations between endogenous estrogen exposure indicators and risk of subtypes of dementia have been unclear.

METHODS

Databases (PubMed, EMBASE and Web of Science) were searched electronically on 1st July and updated regularly until 12nd November 2021. Observational studies of English language were selected if reported an effect estimate [e.g., odds ratio (OR), rate ratio (RR) or hazard ratio (HR)] and 95% CI for the association between any exposure (age of menarche, age at menopause, reproductive period, estradiol level) and any endpoint variable [all-cause dementia, Alzheimer's disease (AD), vascular dementia (VD), cognitive impairment (CI)]. Random-effects models and dose-response meta-analyses were used to calculate estimates and to show the linear/nonlinear relationship. PROSPERO CRD42021274827.

FINDINGS

We included 22 studies (475 9764 women) in this analysis. We found no clear relationship between late menarche (≥14 vs <14 years) and dementia, CI in categorical meta-analysis compared to a J-shape relationship in dose-response meta-analyses. Later menopause (≥45 vs <45 years) was consistently associated with a lower risk of all-cause dementia (pooled RR: 0.87, 95%CI: 0.78-0.97, I=56.0%), AD (0.67, 0.44-0.99, I=78.3%), VD (0.87, 0.80-0.94) and CI (0.82, 0.71-0.94, I=19.3%) in categorical meta-analysis, showing similar results in dose-response meta-analyses. An inverse relationship between longer reproductive duration (≥35 vs <35 years) and dementia was observed in dose-response meta-analysis. In addition, estradiol levels after menopause were inversely correlated with the risk of AD and CI.

INTERPRETATION

In this study, later menopause and longer reproductive period were associated with a lower risk of dementia, while the relationship for menarchal age was J-shaped. There was an inverse relationship between higher postmenopausal estrogen levels and risk of AD and CI. Longitudinal study are needed to further explore the association between life-time estrogen exposure and risk of subtypes of dementia.

FUNDING

Start-up Foundation for Scientific Research in Shandong University.

摘要

背景

内源性雌激素暴露指标与痴呆亚型风险之间的关联尚不清楚。

方法

于2021年7月1日通过电子方式检索数据库（PubMed、EMBASE和Web of Science），并定期更新至2021年11月12日。纳入以英文发表的观察性研究，若其报告了任何暴露因素（初潮年龄、绝经年龄、生育期、雌二醇水平）与任何终点变量[全因性痴呆、阿尔茨海默病（AD）、血管性痴呆（VD）、认知障碍（CI）]之间关联的效应估计值[如比值比（OR）、率比（RR）或风险比（HR）]及95%置信区间。采用随机效应模型和剂量反应荟萃分析来计算估计值并显示线性/非线性关系。国际前瞻性系统评价注册库编号：CRD42021274827。

结果

本分析纳入了22项研究（4759764名女性）。我们发现，在分类荟萃分析中，初潮较晚（≥14岁与<14岁相比）与痴呆、CI之间无明确关联，而在剂量反应荟萃分析中呈J形关系。在分类荟萃分析中，绝经较晚（≥45岁与<45岁相比）始终与全因性痴呆风险较低相关（合并RR：0.87，95%CI：0.78 - 0.97，I² = 56.0%）、AD（0.67，0.44 - 0.99，I² = 78.3%）、VD（0.87，0.80 - 0.94）和CI（0.82，0.71 - 0.94，I² = 19.3%）相关，在剂量反应荟萃分析中显示出类似结果。在剂量反应荟萃分析中观察到生育期较长（≥35年与<35年相比）与痴呆之间呈负相关。此外，绝经后雌二醇水平与AD和CI风险呈负相关。