Brain iron deposition mediates cognitive impairment in COPD: A possible imaging marker linking systemic inflammation to neurodegeneration.

Authors

Qian Chen, Tianlu Teng, Wenyu Zhou, Yu Zhang, Jingting Sun, Ziyi Jing, Ling Wang, Xuejing Li, Lucas Becker, Huan Ye, Zhenghan Yang, Hongjiang Wei, Zhenchang Wang

Published in

Pulmonology. Volume 32. Issue 1. Pages 2704429. Dec 31, 2026. Epub Jul 17, 2026.

Abstract

Cognitive impairment is a relatively prevalent comorbidity in chronic obstructive pulmonary disease (COPD), yet its neuropathological mechanism remains poorly understood.
We enrolled 48 stable COPD patients, categorized into cognitively normal (CogN, n = 22) and impaired (Cog, n = 26) groups based on Montreal Cognitive Assessment (MoCA) scores, along with 34 matched healthy controls. All participants underwent 3T MRI with quantitative susceptibility mapping (QSM) to quantify regional brain iron content. Group comparisons of whole-brain and region-of-interest susceptibility were performed. Mediation analysis was then used to test whether specific brain iron deposition mediates the relationship of both COPD status and peripheral inflammatory markers with cognitive performance.
Cog patients showed increased total iron in the right cerebellum crus I, while CogN patients exhibited higher paramagnetic susceptibility (χpara) in the left orbitofrontal cortex (OFC), right precentral gyrus, and right brainstem. χ_para in the left OFC and right brainstem were positively correlated with total MoCA, abstraction, and orientation scores. Mediation analysis demonstrated that χpara of the left OFC mediated the effects of both COPD status and systemic neutrophil counts on impaired abstraction. Additionally, right brainstem χ_para mediated the relationship between COPD and deficits in orientation.
COPD patients with cognitive impairment exhibited distinct patterns of brain iron deposition. Importantly, deposition in several key regions served as a potential mediator, linking both COPD and systemic inflammation to specific cognitive deficits. These preliminary findings suggest a possible association between brain iron accumulation and cognitive impairment in COPD, offering candidate neuroimaging markers for early identification.  .

PMID:
42464739
Bibliographic data and abstract were imported from PubMed on 17 Jul 2026.

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