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.

Figure 1

QCT evaluation using 3D slicer software. (A and B) Density evaluation based on %LAA₋₉₅₀ after lung segmentation to define emphysema. (C) Airway evaluation in the third generation of the right lung resulting in %WA. (D) An HRCT axial view, mediastinum window to measure PA:A ratio and (E) Measurement PMA and PMD on the level right above the aortic arch showing pectoralis muscle segmentation (bright red = major pectoralis muscle; brownish red = minor pectoralis muscle).

Figure 2

Path analysis model with cognitive impairment. Both %LAA₋₉₅₀ and education duration directly and indirectly through FEV₁ pp contribute to CI development.

Figure 3

Proposed Mechanism of CI Development in COPD. ① Duration of education affects directly in CI, ② Duration of education affects indirectly in CI through FEV₁ pp, ③ FEV₁ pp affects directly in CI, ④ %LAA indirectly affects in CI through FEV₁ pp, ⑤ %LAA directly affects in CI, ⑥ Chronic cellular hypoxia and low-grade inflammation induce HIF-1α expression that cause neuron cell apoptosis and CI, ⑦ BMI correlates with CI, ⑧ Duration of COPD correlates with CI, ⑨ Duration of COPD that correlates with %WA, PA:A, and PM, ⑩ Age correlates with HIF-1α, ⑪ Duration of COPD correlates with CI, ⑫ Age correlates with FEV₁, ⑬ Duration of COPD correlates with FEV₁, ⑭ BMI correlates with FEV₁.