Brain Structure and Function in Chronic Obstructive Pulmonary Disease

Abstract

Brain pathology is a poorly understood systemic manifestation of chronic obstructive pulmonary disease (COPD). Imaging techniques using magnetic resonance (MR) diffusion tensor imaging (DTI) and resting state functional MR imaging (rfMRI) provide measures of white matter microstructure and gray functional activation, respectively. We hypothesized that patients with COPD would have reduced white matter integrity and that functional communication between gray matter resting-state networks would be significantly different to control subjects. In addition, we tested whether observed differences related to disease severity, cerebrovascular comorbidity, and cognitive dysfunction. DTI and rfMRI were acquired in stable nonhypoxemic patients with COPD (n = 25) and compared with age-matched control subjects (n = 25). Demographic, disease severity, stroke risk, and neuropsychologic assessments were made. Patients with COPD (mean age, 68; FEV(1) 53 ± 21% predicted) had widespread reduction in white matter integrity (46% of white matter tracts; P < 0.01). Six of the seven resting-state networks showed increased functional gray matter activation in COPD (P < 0.01). Differences in DTI, but not rfMRI, remained significant after controlling for stroke risk and smoking (P < 0.05). White matter integrity and gray matter activation seemed to account for difference in cognitive performance between patients with COPD and control subjects. In stable nonhypoxemic COPD there is reduced white matter integrity throughout the brain and widespread disturbance in functional activation of gray matter, which may contribute to cognitive dysfunction. White matter microstructural integrity but not gray matter functional activation is independent of smoking and cerebrovascular comorbidity. The mechanisms remain unclear, but may include cerebral small vessel disease caused by COPD.