DNA damage in dementia: Evidence from patients affected by severe Chronic Obstructive Pulmonary Disease (COPD) and meta-analysis of most recent literature

Abstract

Oxidative stress that leads to oxidatively damaged DNA, plays a crucial role in chronic obstructive pulmonary disease (COPD) as well as in the onset of neurodegenerative diseases. The consequent genomic instability is the first neuropathological event found in the preclinical phase of cognitive impairment (CI), and the level of DNA damage is closely related to the degree of dementia. Since CI has been associated with COPD, we investigated the extent of DNA damage in isolated lymphocytes with the Comet assay, in a group of severe COPD patients with cognitive function measured by the Mini-Mental State Examination (MMSE). An increase in DNA damage was observed in COPD patients with dementia (MMSE≤24), although the difference was only borderline (22.4 ± 6.9 vs. 18.5 ± 7.1; p = 0.055). Meta-analysis, including the results of the current study, confirmed that patients with MMSE≤ 24 showed higher level of DNA damage than patients with MMSE> 24. We observed a significant reduction (p < 0.001) in the MMSE score in patients with cognitive decline in areas I (Orientation), III (Attention and Calculus) and V (Language). Only the temporal orientation category in area I was also associated with the level of oxidative damage, with higher levels of MDA (p < 0.01) and DNA damage (p < 0.03). Patients with the lowest temporal orientation score had a 12% higher mean DNA damage (Odds Ratio=1.12; 95% confidence interval (95%CI) 1.01–1.25; p < 0.036). Temporal orientation is a component of most screening tests for the diagnosis of cognitive impairment, on the bases that disorientation is a common factor in dementia. Present results show that each component of cognitive decline can have a different etiopathogenesis and clinical relevance. A more thorough assessment of the cognitive functions of patients starting COPD rehabilitation, together with the assessment of DNA and the level of oxidative stress, can provide essential information to adapt and customize the rehabilitation project.