Association of pulmonary function with the risk of incident Alzheimer’s disease: a prospective cohort and Mendelian randomization study

IF 3.4 3区医学 Q2 GERIATRICS & GERONTOLOGY

Aging Clinical and Experimental Research Pub Date : 2025-08-13 DOI:10.1007/s40520-025-03151-z

Ya-Nan Zheng, Peng Qiu, Hui-Huan Luo, Ren-Jie Chen, Xue-Qiang Wang, Pei-Jie Chen

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引用次数: 0

Abstract

Introduction

The causal association between pulmonary function and Alzheimer’s disease (AD) remains unclear. This study aimed to investigate whether low pulmonary function has a causal relationship with the risk of AD.

Methods

We conducted prospective cohort and two-sample Mendelian randomization (MR) studies. In the cohort study, 333,816 UK Biobank participants were eligible for analysis. Forced expiratory volume in the first second (FEV₁), forced vital capacity (FVC), FEV₁/FVC ratio, percentage of predicted normal value of FEV₁ (FEV₁% pred), and peak expiratory flow (PEF) were measured at baseline. Longitudinal associations were investigated using cox-proportional hazard models. We conducted univariate and multivariable MR analyses on genome-wide association study (GWAS) data from 421,986 Europeans for FEV₁, FVC, and PEF. Inverse-variance weighting was employed as the primary MR analysis approach.

Results

Over a median follow-up of 12.8 years (10.3–15.0 years), 2275 incident cases of AD were identified in the cohort study. Compared to the highest quartile, the lowest quartile for pulmonary function exhibited a higher risk of incident AD, and hazard ratios (95% CI) were as follows after adjustment for risk factors: 1.81 (1.32–2.48; FEV₁), 1.97 (1.44–2.69; FVC), and 1.86 (1.39–2.47; PEF). In the MR study, genetically determined high FEV₁ was associated with a decreased risk of AD (odds ratio: 0.68, 95% CI: 0.53–0.88). The results remained robust after sensitivity and multivariable MR analyses.

Conclusion

Our findings suggest the potential causal association between high FEV₁ and decreased risk of AD.

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肺功能与阿尔茨海默病发生风险的关联：一项前瞻性队列和孟德尔随机化研究

肺功能与阿尔茨海默病（AD）之间的因果关系尚不清楚。本研究旨在探讨肺功能低下是否与AD风险存在因果关系。方法采用前瞻性队列和双样本孟德尔随机化（MR）研究。在队列研究中，333,816名英国生物银行参与者有资格进行分析。在基线时测量第一秒用力呼气量（FEV1）、用力肺活量（FVC）、FEV1/FVC比值、FEV1预测正常值的百分比（FEV1% pred）和呼气峰流量（PEF）。采用协比例风险模型调查纵向关联。我们对421,986名欧洲人FEV1、FVC和PEF的全基因组关联研究（GWAS）数据进行了单变量和多变量MR分析。采用反方差加权作为主要的MR分析方法。结果在中位随访12.8年（10.3-15.0年）期间，队列研究共发现2275例AD病例。与最高四分位数相比，肺功能最低四分位数显示出更高的AD发生风险，危险因素调整后的风险比（95% CI）如下：1.81 (1.32-2.48；Fev1), 1.97 (1.44-2.69；FVC)和1.86 (1.39 ~ 2.47；PEF)。在MR研究中，基因决定的高FEV1与AD风险降低相关（优势比：0.68,95% CI: 0.53-0.88）。在敏感性和多变量MR分析后，结果仍然稳健。结论本研究提示高FEV1与AD风险降低之间存在潜在的因果关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Aging Clinical and Experimental Research 医学-老年医学

CiteScore

7.90

自引率

5.00%

发文量

283

审稿时长

1 months

期刊介绍： Aging clinical and experimental research offers a multidisciplinary forum on the progressing field of gerontology and geriatrics. The areas covered by the journal include: biogerontology, neurosciences, epidemiology, clinical gerontology and geriatric assessment, social, economical and behavioral gerontology. “Aging clinical and experimental research” appears bimonthly and publishes review articles, original papers and case reports.