Brain structural changes in COPD patients with cognitive impairment

Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a systemic condition associated with an elevated risk of cognitive impairment, particularly in domains of executive function and attention, presenting a pattern distinct from Alzheimer's disease. This review synthesizes evidence from multimodal neuroimaging studies to characterize the cerebral alterations in COPD and frame them within the context of accelerated brain aging. Patients with COPD exhibit widespread structural brain changes, including reduced gray matter volume in cognitively critical regions, such as prefrontal cortex, cingulate gyrus, hippocampus, and basal ganglia. Concurrently, white matter damage is evident as microstructural abnormalities in tracts including the cingulum bundle and corona radiata, alongside white matter hyperintensities. These microstructural abnormalities are characterized by decreased fractional anisotropy and increased mean diffusivity. Furthermore, neurovascular uncoupling, indicated by an imbalanced ratio of cerebral blood flow to degree centrality in frontal-temporal areas, contributes to network inefficiency. These neuroimaging abnormalities are closely associated with deficits in executive function, attention, and visuospatial abilities. The underlying pathophysiology involves synergistic effects of systemic hypoxia, chronic inflammation, and neurovascular-coupling dysfunction, which collectively promote a cascade of brain injury resembling accelerated aging. Elucidating this unique neuropathological profile not only enhances the understanding of COPD-related cognitive decline but also highlights potential shared mechanisms with broader brain aging processes, offering insights for early diagnosis and targeted intervention strategies.