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肺功能、COPD 和认知功能:多变量和两样本 Mendelian 随机研究。

Lung function, COPD and cognitive function: a multivariable and two sample Mendelian randomization study.

机构信息

MRC Integrative Epidemiology Unit (IEU), University of Bristol, Oakfield Grove, Bristol, BS8 2BN, UK.

Academic Respiratory Unit, Southmead Hospital, University of Bristol, Bristol, BS10 5NB, UK.

出版信息

BMC Pulm Med. 2021 Jul 22;21(1):246. doi: 10.1186/s12890-021-01611-6.

Abstract

BACKGROUND

Observational studies show an association between reduced lung function and impaired cognition. Cognitive dysfunction influences important health outcomes and is a precursor to dementia, but treatments options are currently very limited. Attention has therefore focused on identifying modifiable risk factors to prevent cognitive decline and preserve cognition. Our objective was to determine if lung function or risk of COPD causes reduced cognitive function using Mendelian randomization (MR).

METHODS

Single nucleotide polymorphisms from genome wide association studies of lung function and COPD were used as exposures. We examined their effect on general cognitive function in a sample of 132,452 individuals. We then performed multivariable MR (MVMR), examining the effect of lung function before and after conditioning for covariates.

RESULTS

We found only weak evidence that reduced lung function (Beta - 0.002 (SE 0.02), p-value 0.86) or increased liability to COPD (- 0.008 (0.008), p-value 0.35) causes lower cognitive function. MVMR found both reduced FEV and FVC do cause lower cognitive function, but that after conditioning for height (- 0.03 (0.03), p-value 0.29 and - 0.01 (0.03) p-value 0.62, for FEV1 and FVC respectively) and educational attainment (- 0.03 (0.03) p-value 0.33 and - 0.01 (0.02), p-value 0.35) the evidence became weak.

CONCLUSION

We did not find evidence that reduced lung function or COPD causes reduced cognitive function. Previous observational studies are probably affected by residual confounding. Research efforts should focus on shared risk factors for reduced lung function and cognition, rather than lung function alone as a modifiable risk factor.

摘要

背景

观察性研究表明,肺功能下降与认知障碍有关。认知功能障碍会影响重要的健康结果,并且是痴呆症的前兆,但目前治疗选择非常有限。因此,人们的注意力集中在确定可改变的危险因素上,以预防认知能力下降和保护认知能力。我们的目的是使用孟德尔随机化(MR)确定肺功能或 COPD 风险是否导致认知功能下降。

方法

使用来自肺功能和 COPD 全基因组关联研究的单核苷酸多态性作为暴露因素。我们在 132452 名个体的样本中检查了它们对一般认知功能的影响。然后,我们进行了多变量 MR(MVMR),在考虑协变量后检查了肺功能对认知功能的影响。

结果

我们发现,只有微弱的证据表明肺功能降低(Beta-0.002(SE 0.02),p 值 0.86)或 COPD 易感性增加(-0.008(0.008),p 值 0.35)导致认知功能下降。MVMR 发现,降低的 FEV 和 FVC 确实会导致认知功能下降,但在考虑身高条件后(FEV1 和 FVC 分别为-0.03(0.03),p 值 0.29 和-0.01(0.03),p 值 0.62)和教育程度(-0.03(0.03),p 值 0.33 和-0.01(0.02),p 值 0.35),证据变得微弱。

结论

我们没有发现证据表明肺功能下降或 COPD 导致认知功能下降。以前的观察性研究可能受到残余混杂因素的影响。研究应集中在降低肺功能和认知能力的共同危险因素上,而不仅仅是将肺功能作为可改变的危险因素。

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