Modeling the impact of COPD on the brain

Original Research

(2537) Views  (608) Full article downloads

Authors: Soo Borson, James Scanlan, Seth Friedman, Elizabeth Zuhr, Julie Fields, et al

Published Date October 2008 Volume 2008:3(3) Pages 429 - 434

DOI: http://dx.doi.org/10.2147/COPD.S2066

Soo Borson¹, James Scanlan¹, Seth Friedman², Elizabeth Zuhr1, Julie Fields³, Elizabeth Aylward^1,2, 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