Distinct neural substrates of disease severity and cognitive impairment in COPD: a multimodal MRI study

BACKGROUND: The neural substrates distinguishing Chronic Obstructive Pulmonary Disease (COPD) patients with mild cognitive impairment (MCI) from those with preserved cognition are not fully understood. This study aims to investigate the distinct neural substrates associated with disease severity and cognitive impairment in COPD using multimodal MRI. METHODS: Thirty-three COPD patients with MCI (COPD-MCI), 30 cognitively normal patients (COPD-nMCI), and 34 healthy controls underwent structural and functional MRI. Voxel-Based Morphometry (VBM) and seed-based Functional Connectivity (FC) analyses identified gray matter volume (GMV) and network alterations. Diagnostic utility was evaluated using ROC analysis. RESULTS: Common to all COPD patients, GMV atrophy and reduced FC in the sensorimotor network (left postcentral gyrus/inferior parietal lobule) were observed, correlating with disease duration (r = -0.523) and distinguished patients from healthy controls (cross-validated AUC = 0.746). Notably, the MCI subgroup was characterized by focal atrophy in the left thalamus and functional decoupling within the visual association network. Visual network FC served as a robust discriminator between the two COPD subgroups (cross-validated AUC = 0.833) and correlated with MoCA scores (r = 0.585). Additionally, reduced fronto-striatal connectivity was observed in the MCI group, while its integrity correlated with lung function in the nMCI group (r = 0.666). CONCLUSIONS: Our findings suggest distinct substrates underlying clinical heterogeneity in COPD. Sensorimotor alterations likely reflect a generalized disease trait of chronic respiratory burden, whereas the integrity of higher-order associative networks, involving the thalamus, visual, and fronto-striatal circuits, acts as a critical checkpoint against cognitive decline. These findings offer novel biomarkers for the early detection of COPD-related cognitive impairment.