Genetic evidence on the association between pulmonary function and cognitive impairment: A 2-sample Mendelian...

Area of Science:

• Genetics
• Pulmonology
• Neurology

Background:

• Observational studies suggest a link between reduced pulmonary function and cognitive decline, but evidence is inconclusive.
• Forced vital capacity (FVC) is a key indicator of lung function, reflecting overall lung capacity.
• Investigating this association using genetic methods can help establish causality.

Purpose of the Study:

• To investigate the causal relationship between forced vital capacity (FVC) and various dementia and cognitive outcomes using Mendelian randomization (MR).
• To assess the association between genetically predicted FVC and 6 dementia types and 6 cognitive domains.
• To provide robust genetic evidence on the pulmonary function-cognition link.

Main Methods:

• Two-sample Mendelian randomization (MR) analyses were conducted.
• Genetic variants associated with FVC were used as instrumental variables.
• Inverse-variance weighted (IVW) method was the primary analysis, with sensitivity analyses including MR-Egger, weighted median, and MR-PRESSO.
• FDR correction, colocalization, and reverse MR analyses were performed to ensure robustness.

Main Results:

• Higher genetically predicted FVC was significantly associated with a lower risk of Alzheimer disease (AD) (log-OR = -0.24, FDR-adjusted P = 0.011).
• An inverse association was observed for all-cause dementia, but it did not meet statistical significance after FDR correction (FDR-adjusted P = 0.094).
• No significant associations were found for other dementia subtypes or cognitive outcomes.

Conclusions:

• This study provides genetic evidence supporting an association between reduced pulmonary function (FVC) and cognitive impairment, particularly AD.
• The findings highlight the potential role of lung health in maintaining cognitive function.
• Further research is necessary to elucidate the underlying biological mechanisms connecting FVC and cognitive decline.