Modeling the impact of COPD on the brain

Abstract

Previous studies have shown that COPD adversely affects distant organs and body systems, including the brain. This pilot study aims to model the relationships between respiratory insufficiency and domains related to brain function, including low mood, subtly impaired cognition, systemic inflammation, and brain structural and neurochemical abnormalities. Nine healthy controls were compared with 18 age- and education-matched medically stable COPD patients, half of whom were oxygen-dependent. Measures included depression, anxiety, cognition, health status, spirometry, oximetry at rest and during 6-minute walk, and resting plasma cytokines and soluble receptors, brain MRI, and MR spectroscopy in regions relevant to mood and cognition. ANOVA was used to compare controls with patients and with COPD subgroups (oxygen users [n = 9] and nonusers [n = 9]), and only variables showing group differences at p ≤ 0.05 were included in multiple regressions controlling for age, gender, and education to develop the final model. Controls and COPD patients differed significantly in global cognition and memory, mood, and soluble TNFR1 levels but not brain structural or neurochemical measures. Multiple regressions identified pathways linking disease severity with impaired performance on sensitive cognitive processing measures, mediated through oxygen dependence, and with systemic inflammation (TNFR1), related through poor 6-minute walk performance. Oxygen desaturation with activity was related to indicators of brain tissue damage (increased frontal choline, which in turn was associated with subcortical white matter attenuation). This empirically derived model provides a conceptual framework for future studies of clinical interventions to protect the brain in patients with COPD, such as earlier oxygen supplementation for patients with desaturation during everyday activities.

Neurocognitive Impairment as Systemic Effects of COPD

“…Neuroimaging studies showed there are signiicantly lowered gray mater volumes in several brain regions as hippocamp [7], limbic and paralimbic structures [77], precuneus, bilateral calcarine, right superior temporal gyrus/middle temporal gyrus, bilateral fusiform, right inferior parietal lobule [78], cingulate and amygdala [8], dorsolateral prefrontal cortex [77] etc., evidenced by diferent neuroimaging techniques based on magnetic resonance imaging (MRI). Performance accuracy has increased by introducing voxel-based morphometry analysis also based on MRI.…”

“…The efort in daily activities would be likely to cause brain damage in severe COPD hypoxemic patients; emphasizing desaturations, inducing increase of frontal lobes choline (which is a reliable marker of myelin destruction with alteration of neuronal membrane turnover) corresponding to white mater hyperintensities on magnetic resonance imaging (MRI) [7].…”

“…Therefore, continuous or even intermitent hypoxia (eforts, daily activities and sleep) may cause changes in brain perfusion, transient deicits in neurotransmiter metabolism in the central nervous system with changes in brain neurochemistry and structure [7,36,[40][41][42].…”

“…From the point of view of the hypoxemia approach, the answer to this debate will have to consider the evidence: (1) one in four people with COPD have cognitive impairment and over time, cognitive decline will deepen (risking an evolution toward multi-infarct dementia or Alzheimer disease) [92][93][94]. (2) It is now recognized that not only continuous, but also intermitent hypoxia (eforts, daily activities and sleep) can by repetition cause changes in brain neurochemistry and structure [7,36]. Regular use of supplemental oxygen therapy has been shown to decrease the risk for cognitive impairment in patients with COPD [37,38,95].…”

Trends in the use of preconditioning to hypoxia for early prevention of future life diseases

“…The newborns with congenital heart disease (45,46). For other diseases, changes have been found in adult brain for type 2 diabetes (47-50), asthma (51,52), and chronic obstructive pulmonary disease (53)(54)(55). Improvements in diagnostic methods will make it possible to establish changes during early life.…”