Chronic hypoxia-hypercapnia influences cognitive function: A possible new model of cognitive dysfunction in chronic obstructive pulmonary disease
Introduction
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of chronic morbidity and mortality [1]. Although airflow obstruction is the most obvious manifestation of COPD, it is associated with many extrapulmonary features that contribute to the morbidity, reduced quality of life, and mortality [2], such as fatigue, anxiety disorders, depression and cognitive impairment. Although psychological processes are more or less ignored in medical and treatment guides [1], cognitive impairment has been documented as one of the important extrapulmonary manifestation in patients with COPD [2]. Several researches have indicated a prevalence of psychological disorders in patients with COPD. In particular, the incidence of cognitive impairment has been found to be elevated in this population [3]. Cognitive impairment is an important part of life quality in patients with COPD. Prospective cohort study showed that moderate-to-severe cognitive impairment was associated with an increased risk of mortality, even after controlling for confounding effects of demographic and clinical characteristics [4]. Therefore, cognitive dysfunction is common and clinically important in patients with COPD.
The previous studies suggest that chronic hypoxia, chronic hypercapnia, or both contribute importantly to the development of pathophysiology in COPD. The natural history of COPD is characterized by progressive decrements in expiratory airflow, increments in end-expired pulmonary volume, hypoxaemia, hypercapnia, progression of pulmonary hypertension [5] and cor pulmonale. Alveolar hypoxia is thought to be a key stimulus to the development of pulmonary hypertension. The mechanisms of hypoxia induced pulmonary hypertension are supported by vast literature. In patients with COPD, ventilatory failure leading to chronic hypercapnia in association with hypoxia is a common complication and it is a well-established clinical observation that significant pulmonary hypertension does not develop in the presence of hypoxic lung disease unless hypercapnia is also present [6], [7]. A close correlation has been noted between the arterial CO2 tension and the pulmonary arterial pressure in this setting [7].
Previous studies showed that clinicians have recognized for some time that patients with advanced COPD can develop delirium or intellectual impairment secondary to hypoxia and hypercarbia [8]. In hypoxemic COPD patients, the mechanism of neuronal damage is well established. Progressive hypoxia leads to an increase in blood viscosity and pulmonary vascular resistance which result in cor pulmonale and a decrease in cerebral perfusion [9]. In hypoxic-hypercapnic COPD patients, Incalzi et al. [10] found a distinct cognitive profile was found in a large fraction of patients with hypoxic-hypercapnic COPD and it differs in several aspects from those of both normal and demented subjects. The title was “Chronic obstructive pulmonary disease. An original model of cognitive decline”.
Section snippets
Hypothesis
We hypothesize that chronic hypoxia-hypercapnia may result in a significant influences on cognitive functions. We suggest that cognitive impairment is closely related with the combination of chronic hypoxia and hypercapnia in patients with COPD. Chronic hypoxia-hypercapnia induced cognitive dysfunction in animal models may mimic the cognitive impairment in patients with COPD, which could possibly be used for the fundamental research of mechanism.
Discussion
This hypothesis has some guidences for the pathogenesis, diagnosis and treatment of cognitive impairment in patients with COPD.
Firstly, many findings suggested that the degree of hypoxemia is correlated with cognitive impairment in patients with COPD. A pilot study [11]explored the analogy exists between cognitive impairment in hypoxemic COPD and Alzheimer’s disease (AD),and found that anterior cerebral hypoperfusion and selected neuropsychological dysfunctions characterized hypoxemic COPD
Acknowledgement
This work is supported by the Natural Science Foundation of Zhejiang province of China (Y2004A017).
References (15)
- et al.
Brain dysfunction in COPD
Chest
(1980) - et al.
Cognitive performance in patients with COPD
Respir Med
(2004) - et al.
Brief cognitive screening measures in patients with chronic obstructive pulmonary disease
Arch Clin Neuropsychol
(1999) - Global Initiative for Chronic Obstructive Lung Disease. Pocket guide to COPD diagnosis, management, and prevention....
- et al.
Brain perfusion abnormalities in chronic obstructive pulmonary disease: comparison with cognitive impairment
Ann Nucl Med
(2006) - et al.
Screening of cognitive impairment in chronic obstructive pulmonary disease
Dement Geriatr Cogn Disord
(2007) - et al.
Cognitive impairment and mortality in older primary care patients
J Am Geriatr Soc
(2001)
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