Modeling the impact of COPD on the brain
Soo Borson1, James Scanlan1, Seth Friedman2, Elizabeth Zuhr1, Julie Fields3, Elizabeth Aylward1,2, Rodney Mahurin2, Todd Richards2, Yoshimi Anzai2, Michi Yukawa4, Shingshing Yeh5
1Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA; 2Radiology Department, University of Washington, Seattle, Washington, USA; 3Department of Psychology (Neuropsychology), University of Texas Southwestern Medical Center, Texas, USA; 4Department of Medicine (Geriatrics), University of Washington, Seattle, WA, USA; 5Department of Medicine (Geriatrics), Veterans Affairs Medical Center, Northport, New York, USA
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.
Keywords: oxygen desaturation, frontal choline, cognition, mood, SGRQ, cytokines
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