A Multicenter Study of COPD and Cognitive Impairment: Unraveling the Interplay of Quantitative CT, Lung Function, HIF-1α, and Clinical Variables

Abstract

Purpose

The exact link between cognitive impairment (CI) and chronic obstructive pulmonary disease (COPD) is still limited. Thus, we aim to find the relationship and interaction of quantitative CT (QCT), lung function, HIF-1α, and clinical factors with the development of CI among COPD patients.

Patients and Methods

A cross-sectional multicentre study was conducted from January 2022 to December 2023. We collected clinical data, spirometry, CT images, and venous blood samples from 114 COPD participants. Cognitive impairment assessment using the Montreal Cognitive Assessment Indonesian version (MoCA-Ina) with a cutoff value 26. The QCT analysis consists of lung density, airway wall thickness, pulmonary artery-to-aorta ratio (PA:A), and pectoralis muscles using 3D Slicer software. Serum HIF-1α analysis was performed using ELISA.

Results

We found significant differences between %LAA₋₉₅₀, age, COPD duration, BMI, FEV₁ pp, and FEV₁/FVC among GOLD grades I–IV. Only education duration was found to correlate with CI (r = 0.40; p < 0.001). We found no significant difference in HIF-1α among GOLD grades (p = 0.149) and no correlation between HIF-1α and CI (p = 0.105). From multiple linear regression, we observed that the MoCA-Ina score was influenced mainly by %LAA₋₉₅₀ (p = 0.02) and education duration (p = 0.01). The path analysis model showed both %LAA and education duration directly and indirectly through FEV₁ pp contributing to CI.

Conclusion

We conclude that the utilization of QCT parameters is beneficial as it can identify abnormalities and contribute to the development of CI, indicating its potential utility in clinical decision-making. The MoCA-Ina score in COPD is mainly affected by %LAA₋₉₅₀ and education duration. Contrary to expectations, this study concludes that HIF-1α does not affect CI among COPD patients.

Keywords:

• chronic obstructive pulmonary disease
• cognitive impairment
• emphysema lung
• hypoxia inducible factor

Ethical Approval and Consent to Participate

This study received two ethical approvals, that is, Ethical Committee of Persahabatan Hospital (no: 02/KEPK-RSUPP/01/2022), which allow us to recruit participants from Persahabatan Hospital from January 2022. Another ethical approval released by Faculty of Medicine, University of Indonesia (no: KET-133/UN2.F1/ETIK/PPM.00.02/2022), which allow us to recruit participants from three other hospitals (Cipto Mangunkusumo Hospital, Gatot Soebroto Army Hospital, and Jakarta Islamic Hospital Cempaka Putih) from February 2022. All procedures used in this study adhered to the institutional and national research committee’s ethical requirements and the Declaration of Helsinki. All participants in this study are adults and have given a written informed consent before enrolled in this study.

Acknowledgments

We are grateful to all participants of the project and the research members for their valuable contributions and assistance with the data collection process so that we can complete this scientific paper.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors.