脑卒中亚型后痴呆的负担：一项整合GBD数据库和孟德尔随机化的研究

IF 1.8 4区医学 Q3 NEUROSCIENCES

Journal of Stroke & Cerebrovascular Diseases Pub Date : 2025-08-27 DOI:10.1016/j.jstrokecerebrovasdis.2025.108443

Meng Jin , Jingjing Liu , Ziyi Bao , Xiaqing Hong , Songbin He , Feng Gao

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引用次数: 0

摘要

大量的研究已经建立了中风和痴呆之间的因果关系，并分别证明了缺血性或出血性中风和全因痴呆之间有很强的相关性。鉴于全球范围内全因痴呆的总体患病率不断上升，且缺乏随机临床试验数据证实存在有效的痴呆干预措施。本文的目的是应用GBD数据库估计全球和区域内缺血性和出血性中风后痴呆的比例和趋势，并使用孟德尔随机化（MR）讨论血管性痴呆的潜在危险因素。方法通过文献回顾和贝叶斯回归分析，我们估计缺血性和出血性卒中后痴呆的相对风险。然后结合全球疾病负担研究（GBD）疾病负担数据，计算脑梗死和脑出血（PAF）导致的痴呆比例以及特定临床病因-年-性别区域下的痴呆负担。并对未来10年进行了预测。使用GWAS数据库，收集血管性痴呆和17种危险因素的数据，并通过双样本MR分析确定因果关系。结果脑出血后痴呆的相对危险度（RR: 3.02[1.17-7.78], p < 0.001）高于脑梗死后痴呆的相对危险度（RR: 2.07[1.47-2.96], p < 0.001）。然而，由于脑梗死的高患病率，脑梗死所致痴呆的PAF高于脑出血。它们加起来解释了全球1.31%（1.41%-1.21%）的痴呆症。脑梗死和脑出血后痴呆的负担表现出明显的时空异质性。四种因果关系在双样本MR中被复制，脑脊液（CSF）代谢物X-11261的中介作用被两步MR确定。解释全球1%的痴呆患病率可以用缺血性中风和出血性中风来解释。量化由这两种情况引起的痴呆的比例有助于我们全面了解痴呆的原因。通过两样本MR研究和两步MR分析，确定与血管性痴呆相关的可改变危险因素和脑脊液介质，阐明预防或延缓痴呆典型特征的干预方法。这对今后的疾病预防和治疗工作至关重要。

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Burden of dementia following stroke subtypes: a study integrating the GBD database and Mendelian randomization

Background

A large number of studies have previously established a causal association between stroke and dementia, and have demonstrated a strong correlation between ischemic or hemorrhagic stroke and all-cause dementia, respectively. Given the overall increasing prevalence of all-cause dementia worldwide and the absence of data from randomized clinical trials confirming the existence of effective dementia interventions.The aim of this paper is to apply the GBD database to estimate the proportion and trends of dementia following ischemic and hemorrhagic strokes globally and within regions, and to discuss potential risk factors for vascular dementia using Mendelian randomization (MR).

METHODS

Using a literature review and Bayesian regression analysis, we estimated the relative risk of dementia following ischemic and hemorrhagic stroke. The proportion of dementia attributable to cerebral infarction and cerebral hemorrhage (PAF) and the burden of dementia under specific clinical etiology-year-sex-region were then calculated in conjunction with the Global Burden of Disease Study (GBD) burden of disease data. And projections were made for the next 10 years. Using the GWAS database, data on vascular dementia and 17 risk factors were collected, and causality was determined by two-sample MR analysis. In addition, potential mediators of risk factor effects on vascular dementia were searched from 338 cerebrospinal fluid metabolites by two-step MR.

RESULTS

The relative risk of dementia following cerebral hemorrhage ( relative risk(RR):3.02[1.17-7.78],P<0.001 ) was higher than that of cerebral infarction (RR: 2.07[1.47-2.96], P<0.001). However, due to the high prevalence of cerebral infarction, the PAF for dementia due to cerebral infarction was higher than that of cerebral hemorrhage. Together, they explain 1.31% (1.41%-1.21%) of global dementia. The burden of dementia following both cerebral infarction and cerebral hemorrhage showed significant spatial and temporal heterogeneity. Four causal associations were replicated in two-sample MR and a mediating role for cerebrospinal fluid(CSF) metabolites X-11261 was identified by 2-step MR.

INTERPRETATION

one point three one percent of dementia prevalence globally could be explained by ischemic stroke and hemorrhagic stroke.Quantifying the proportion of dementia caused by these two conditions has helped us to gain a comprehensive understanding of the causes of dementia.Through two-sample MR study and two-step MR analysis, modifiable risk factors and cerebrospinal fluid mediators associated with vascular dementia were identified, elucidating intervention methods for preventing or delaying the typical characteristics of dementia. This is crucial for future efforts in disease prevention and treatment.

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来源期刊

Journal of Stroke & Cerebrovascular Diseases Medicine-Surgery

CiteScore

5.00

自引率

4.00%

发文量

583

审稿时长

62 days

期刊介绍： The Journal of Stroke & Cerebrovascular Diseases publishes original papers on basic and clinical science related to the fields of stroke and cerebrovascular diseases. The Journal also features review articles, controversies, methods and technical notes, selected case reports and other original articles of special nature. Its editorial mission is to focus on prevention and repair of cerebrovascular disease. Clinical papers emphasize medical and surgical aspects of stroke, clinical trials and design, epidemiology, stroke care delivery systems and outcomes, imaging sciences and rehabilitation of stroke. The Journal will be of special interest to specialists involved in caring for patients with cerebrovascular disease, including neurologists, neurosurgeons and cardiologists.