Oxidative stress, including DNA damage and malondialdehyde, was associated with dementia in patients with chronic obstructive pulmonary disease (COPD).

Patients with chronic obstructive pulmonary disease (COPD) were found to have an association with the condition of dementia through oxidative stress, which includes malondialdehyde (MDA) and DNA damage. The study, published in Mutation Research – Genetic Toxicology and Environmental Mutagensis, also found there was an association between DNA damage and failure in temporal orientation, which may be an indicator of specific cognitive impairment.

The observational study had 96 participants who were aged 65 years and older, were suffering from severe COPD, and were admitted to the Pulmonary Rehabilitation Unit of the IRCCS San Raffaele Roma between January 2013 and December 2015. Demographic information, medical history, lifestyle, and frequency intake of some foods for the patients were collected using a questionnaire.

Cognitive function was assessed using the Mini-Mental State Exam (MMSE) in patients with COPD. The test included assessments on orientation, immediate recall, attention and calculation, recall, and language.

The 96 patients included in this study had a mean (SD) age of 72.0 (8.7) years and were recruited at hospital admission. All patients were classified into 2 groups where 1 group demonstrated signs of cognitive impairment (MMSE less than or equal to 24) and the other didn’t (MMSE greater than 24). The 2 groups had 17 (18%) and 79 (82%) patients respectively.

Patients with an MMSE score less than or equal to 24 demonstrated a higher level of DNA damage than patients with a higher MMSE score (22.4 [6.9] vs 18.5 [7.1]) in a borderline difference that approached statistical significance.

Patients with MMSE less than or equal to 24 also demonstrated a significant reduction in the total score in orientation, attention and calculation, and language on their assessments. There was a significant and consistent difference between the 2 groups only for temporal orientation, which was a sub-category of orientation.

The multivariate logistic regression also found a significant association between DNA damage and a lower MMSE score after adjusting for potential and actual confounders. Comet assay, a blood test, was identified as a significant and independent predictor of cognitive decline (OR, 1.097; 95% CI, 1.012-1.189) in the logistic regression model. Comet assay was also the only predictor of temporal orientation (OR, 1.121; 95% CI, 1.070-1.247) meaning that patients with a lower MMSE score have a 10% higher level of DNA damage.

Patients with an MMSE less than or equal to 24 demonstrated a higher level of DNA damage when compared with participants with normal cognitive function in a meta-analysis (Ratio of Means, 1.54; 1.12-2.10).

There were some limitations to this study. For instance, there was a failure to identify differences in the 2 groups using a different measurement through the ELISA test, which could limit the results.

The researchers concluded that the results of the study combined with the meta-analysis on comet assay studies confirmed that oxidative stress, including MDA and DNA damage, was associated with dementia in patients with COPD, with a specific association between failure in temporal orientation and DNA damage.


Ilari S, Russo P, Proietti S, et al. DNA damage in dementia: evidence from patients affected by severe chronic obstructive pulmonary disease (COPD) and meta-analysis of most recent literature. Mutat Res Genet Toxicol Environ Mutagen. 2022;878:503499. doi:10.1016/j.mrgentox.2022.503499

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