Left precuneus ALFF is associated with arterial oxygenation and cognitive impairment in patients with COPD: a resting-state fMRI study.

BACKGROUND: Cognitive impairment is a common but underrecognized comorbidity in chronic obstructive pulmonary disease (COPD). Lower arterial oxygenation may be associated with altered spontaneous brain activity, but the regional functional correlates linking oxygenation and cognition remain incompletely understood. This study examined amplitude of low-frequency fluctuation (ALFF) abnormalities in COPD patients with cognitive impairment and explored their associations with arterial oxygenation and cognitive performance. METHODS: This cross-sectional study included 90 participants: 30 healthy controls, 30 COPD patients without cognitive impairment, and 30 COPD patients with cognitive impairment. Cognitive status was assessed using the Montreal Cognitive Assessment (MoCA); one point was added for participants with ≤12 years of education, with the adjusted score capped at 30, and an education-adjusted score <26 was used to define cognitive impairment. All participants underwent arterial blood gas analysis and resting-state functional MRI. Whole-brain voxel-wise ALFF differences were evaluated using analysis of covariance, with an uncorrected voxel-wise cluster-forming threshold of p < 0.001; clusters were considered significant at a cluster-level FDR-corrected threshold of p < 0.05. Adjusted regression, restricted cubic spline, and exploratory cross-sectional mediation analyses were performed in patients with COPD. RESULTS: COPD patients with cognitive impairment showed lower ALFF in the left precuneus, left putamen, and bilateral parahippocampal gyri, with all clusters surviving cluster-level FDR correction (P_FDR = 0.004-0.021). Higher PaO₂ was associated with higher MoCA total score and higher ALFF in the left precuneus and left putamen after adjustment for multiple comparisons. Higher regional ALFF was also associated with better cognitive performance, with the strongest association observed in the left precuneus. In an exploratory cross-sectional mediation model, left precuneus ALFF statistically accounted for part of the association between PaO₂ and MoCA total score. CONCLUSION: Reduced left precuneus ALFF may represent a candidate neuroimaging correlate of lower arterial oxygenation and poorer cognitive performance in COPD. Because of the cross-sectional design, the exploratory mediation findings do not establish temporal or causal relationships and require confirmation in larger longitudinal cohorts.