COPD is often considered a disease that solely affects the lungs; however, its extrapulmonary effects are profound and disabling. Our study indicates that COPD is strongly associated with cognitive impairment in a large cohort of patients with a broad range of COPD severity. Resting hypoxemia was the single most important risk factor for cognitive impairment; treatment with supplemental oxygen markedly decreased the risk. Lung function impairment, COPD severity, and cardiovascular disease did not appear to explain the development of cognitive impairment in COPD.
We used a rigorous and multifaceted approach to measuring COPD severity (lung function, COPD Severity Score, and BODE Index). Despite this approach, we found no impact of these indicators of disease severity on the risk of cognitive impairment. This differs from some previous work,41
but is similar to other studies that found no association between disease severity and cognitive impairment.42
Our results reveal a disconnect between global measures of COPD severity, which were not related to cognitive impairment, and decreased resting oxygenation, which was strongly associated with decreased cognitive function.
The specific role of cardiovascular comorbidities as a risk factor for cognitive impairment in COPD is difficult to ascertain as both conditions share risk factors (eg, smoking) and COPD patients may be predisposed to cardiovascular events.18
When cardiovascular comorbidities were evaluated as a risk factor for cognitive impairment, no association was found among the COPD cohort. The point estimate for cardiovascular disease was elevated, however, in the unadjusted analysis, so lack of statistical power may be one explanation for this lack of effect. Controlling for covariates, such as smoking, reduced the effect estimate, so that any association between cardiovascular disease and cognitive impairment may be mediated by smoking and other factors.
Cognitive impairment may interfere with patients’ ability to adhere to their medication regimen, adjust their medications in response to respiratory symptoms, and perform other aspects of self-management. Given that many of the medications for COPD are self-activated, even mild degrees of cognitive impairment could have significant effects on disease management. More broadly, cognitive impairment may create difficulties with performing daily activities, especially those that involve memory or complex reasoning.43
It is likely that cognitive impairment has major effects on many aspects of patient functioning and health status.
The MMSE is a widely used measure of cognitive impairment but it is not sensitive for mild cognitive dysfunction.44
Consequently, our methods could have missed cases of mild cognitive impairment. It remains possible, therefore, that COPD severity could predict milder degrees of cognitive dysfunction. A future analysis of cognitive impairment using a detailed neuropsychologic battery of tests is required to evaluate milder cognitive impairment in COPD.
Our study is subject to several other limitations. Because our primary study focus was development of disability in COPD, we enrolled younger patients (45–65 years). Consequently, our study may underestimate the impact of COPD on cognitive impairment in older patients. Misclassification of COPD could also have occurred. Our COPD definition required concomitant treatment with COPD medications to increase the specificity of our definition. In addition, all patients had a physician diagnosis of COPD and reported having the condition. The lifetime smoking prevalence was similar to that in other population-based epidemiologic studies of COPD, supporting the diagnosis of COPD rather than asthma.46
We also previously demonstrated the validity of our approach using medical record review.18
Nonetheless, we acknowledge this potential limitation.
Another limitation is the small proportion of subjects who were using home oxygen. Consequently, the confidence intervals around our estimates of the effectiveness of oxygen for preventing cognitive impairment are wide in some cases. As the FLOW cohort continues longitudinal follow-up, we will further evaluate the impact of oxygen therapy on cognitive function.
COPD is a multisystem disease with extrapulmonary sequelae. It is strongly associated with an increased risk of cognitive impairment, especially among hypoxemic patients. Clinicians should evaluate their COPD patients for cognitive impairment in order to identify those who may benefit from interventions such as medication assistance or supplemental oxygen therapy. Future research should use detailed neuropsychological testing to carefully evaluate multiple cognitive domains among subjects with a broad range of ages and disease severity.