Contributions of cardiovascular risk and smoking to chronic obstructive pulmonary disease (COPD)-related changes in brain structure and function

Abstract

Catherine A Spilling,1 Mohani-Preet K Bajaj,1 Daniel R Burrage,2 Sachelle Ruickbie,2 N Jade Thai,3 Emma H Baker,2 Paul W Jones,2 Thomas R Barrick,1 James W Dodd41Institute for Molecular and Clinical Sciences, St George’s University of London, London SW17 ORE, UK; 2Institute for Infection and Immunity, St George’s University of London, London SW17 ORE, UK; 3Clinical Research and Imaging Centre, University of Bristol, Bristol BS2 8DX, UK; 4Academic Respiratory Unit, University of Bristol, Bristol BS10 5NB, UKCorrespondence: James W DoddAcademic Respiratory Unit, University of Bristol, Learning & Research Building Southmead Hospital, Bristol BS10 5NB, UKTel [phone]Email [email protected]: Brain damage and cardiovascular disease are extra-pulmonary manifestations of chronic obstructive pulmonary disease (COPD). Cardiovascular risk factors and smoking are contributors to neurodegeneration. This study investigates whether there is a specific, COPD-related deterioration in brain structure and function independent of cardiovascular risk factors and smoking.Materials and methods: Neuroimaging and clinical markers of brain structure (micro- and macro-) and function (cognitive function and mood) were compared between 27 stable COPD patients (age: 63.0±9.1 years, 59.3% male, forced expiratory volume in 1 second [FEV1]: 58.1±18.0% pred.) and 23 non-COPD controls with >10 pack years smoking (age: 66.6±7.5 years, 52.2% male, FEV1: 100.6±19.1% pred.). Clinical relationships and group interactions with brain structure were also tested. All statistical analyses included correction for cardiovascular risk factors, smoking, and aortic stiffness.Results: COPD patients had significantly worse cognitive function (p=0.011), lower mood (p=0.046), and greater gray matter atrophy (p=0.020). In COPD patients, lower mood was associated with markers of white matter (WM) microstructural damage (p<0.001), and lower lung function (FEV1/forced vital capacity and FEV1) with markers of both WM macro (p=0.047) and microstructural damage (p=0.028).Conclusion: COPD is associated with both structural (gray matter atrophy) and functional (worse cognitive function and mood) brain changes that cannot be explained by measures of cardiovascular risk, aortic stiffness, or smoking history alone. These results have important implications to guide the development of new interventions to prevent or delay progression of neuropsychiatric comorbidities in COPD. Relationships found between mood and microstructural abnormalities suggest that in COPD, anxiety, and depression may occur secondary to WM damage. This could be used to better understand disabling symptoms such as breathlessness, improve health status, and reduce hospital admissions.Keywords: chronic lung disease, cigarette smoke, cognition, depression, MRI, neuroimaging

Keywords

• Chronic lung disease
• cigarette smoke
• cognition
• depression
• MRI
• neuroimaging.