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

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 FEV1 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.

Risk of developing cognitive impairment on patients with chronic obstructive pulmonary disease

“…The authors noted that COPD might still have causal effects on certain domains not detected by analysis that had been performed. The use of MR to elucidate causal relationship between COPD and cognitive impairment were evaluated by using Single Nucleotide Polymorphisms (SNPs) and that there were no SNPs which can guarantee future COPD diagnosis although for a binary exposure, MR remains a viable test of the causal null hypothesis [21] . Furthermore, the outcome of this study was performed to evaluate global cognitive function for general population as a contiuous outcome and have not performed evaluation on the impact of lung function on MCI [21] …”

“…Meanwhile, a study design using observational method stilll suffer from its limitation to determine a robust causality evidence between COPD and cognitive impairment primarily due to shared risk factors with smoking. [ 21 ] In recent publications, new approach using Mendelian Randomization (MR) which is a novel epidemiological tool for inferring causation may provide a chance to investigate this significant knowledge gap. [ 22 ] MR is a technique that may be used to circumvent the issues associated with unmeasured confounding and reverse causation that afflict standard observational epidemiology.…”

“…It was then suggested that the results from previous observational studies were more likely influenced by residual confoundings. [ 21 ]…”

“…However, it should be noted that only 1 MR study is available within current publication and that this study is still suffering from several limitations as noted by the authors. [ 21 ] The authors noted that COPD might still have causal effects on certain domains not detected by analysis that had been performed. The use of MR to elucidate causal relationship between COPD and cognitive impairment were evaluated by using Single Nucleotide Polymorphisms (SNPs) and that there were no SNPs which can guarantee future COPD diagnosis although for a binary exposure, MR remains a viable test of the causal null hypothesis.…”

“…[ 21 ] Furthermore, the outcome of this study was performed to evaluate global cognitive function for general population as a contiuous outcome and have not performed evaluation on the impact of lung function on MCI. [ 21 ]…”