title: 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 < or = 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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle,WA, USA. soob@u.washington.edu
authors.forename: Soo
authors.initials: S
authors.lastname: Borson
authors.forename: James
authors.initials: J
authors.lastname: Scanlan
authors.forename: Seth
authors.initials: S
authors.lastname: Friedman
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Zuhr
authors.forename: Julie
authors.initials: J
authors.lastname: Fields
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Aylward
authors.forename: Rodney
authors.initials: R
authors.lastname: Mahurin
authors.forename: Todd
authors.initials: T
authors.lastname: Richards
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Anzai
authors.forename: Michi
authors.initials: M
authors.lastname: Yukawa
authors.forename: Shingshing
authors.initials: S
authors.lastname: Yeh
mesh_terms: D000339:Affect; D000368:Aged; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001927:Brain Diseases / Q000209:etiology; D002794:Choline / Q000378:metabolism; D003071:Cognition; D003072:Cognition Disorders / Q000209:etiology; D018450:Disease Progression; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010092:Oximetry; D010865:Pilot Projects; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D013147:Spirometry
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D002794:Choline