Background Chronic obstructive pulmonary disease (COPD) is a systemic condition that often results in cognitive impairment. Nevertheless, the central nervous system correlates of COPD-related cognitive decline are not well-defined, representing a critical knowledge gap. The present study aimed to investigate the relationship among respiratory symptoms, structural brain changes, and cognitive impairment in patients with COPD who have subclinical cognitive vulnerability (COPD-SCV). Methods This cross-sectional study included 60 patients with stable COPD-SCV and 60 age-, sex-, and education-matched controls. Multimodal magnetic resonance imaging was used to measure cortical thickness, fractional anisotropy (FA), radial diffusivity (RD), and graph-theoretical network metrics. Two tests were used to evaluate cognitive performance: the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The St. George’s Respiratory Questionnaire (SGRQ) was used to estimate respiratory symptoms. To investigate the relationship among respiratory symptoms, structural brain alterations, and cognitive impairment, we conducted correlation and mediation analyses. Results MoCA scores, used as a screening tool, indicated lower cognitive performance in patients with COPD than in healthy controls (25. 03 ± 3. 13 vs. 27. 13 ± 2. 32; p 0. 001), with preliminary observations suggesting potential involvement in memory and visuospatial/executive domains. These deficiencies were accompanied by cortical thinning in the right cuneus, temporal lobe, and supplementary motor area (SMA; p 0. 05), along with white matter disruption (lower FA, higher RD) in corresponding tracts (p 0. 01). Graphical analysis showed decreased degree centrality of the left SMA (SMAL’DC, p = 0. 005) and decreased global network efficiency (p 0. 001). Notably, SMAL’DC was significantly associated with respiratory symptoms (SGRQ) and cognitive performance (MoCA). Using a cross-sectional mediation model, we found that the association between SGRQ and MoCA was significantly accounted for by SMAL’DC (path c: β = −0. 302, p = 0. 019). Specifically, the results supported a statistical mediation model in which SMAL’DC was significantly associated with the pathway linking respiratory symptoms and cognitive function. Conclusion Patients with COPD-SCV exhibit deterioration of grey matter morphology, white matter microstructure, and structural network. The relationship between respiratory symptoms and cognitive impairment shows a statistical association with variations in SMAL connectivity, a key network hub. These findings identify a distinct neuroanatomical phenotype and suggest that SMA connectivity may be a potential imaging marker associated with cognitive risk. However, given the cross-sectional design, these results reflect correlational patterns consistent with a lung–brain axis hypothesis rather than definitive evidence of causation.
Wang et al. (Mon,) studied this question.
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