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ORIGINAL ARTICLE
Cognitive function in chronic obstructive pulmonary disease: Relationship to global initiative for chronic obstructive lung disease 2011 categories BAYKAL TULEK,1 NART BEDIN ATALAY,2 GULFEM YILDIRIM,1 FIKRET KANAT1 AND MECIT SÜERDEM1 1
Department of Chest Diseases, Faculty of Medicine, Selcuk University, Konya and 2Department of Psychology, TOBB University of Economics & Technology, Ankara, Turkey
ABSTRACT Background and objective: Recently, comorbidities such as impaired cognitive function have been attracting more focus when considering the management of chronic obstructive pulmonary disease (COPD). Here we investigated the relationship between cognitive function and the categories given in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in 2011. Specifically, after controlling for non-COPD covariates, we assessed the clinical features that may be predictive of cognitive impairment in patients with COPD. Methods: We recruited 119 stable patients with mild to very severe COPD. We administered a broad array of standardized neuropsychological tests that assessed cognitive functions in the domains of attention, memory, psychomotor coordination and language. Results: Cognitive scores were significantly different between patients falling within GOLD 2011 categories. Scores were lower in patients with high future risk compared with low future risk. In parallel, there were significant differences in cognitive function between COPD patient subgroups when patients were grouped according to the forced expiratory volume in 1 s, exacerbation history and C-reactive protein levels. After controlling for non-COPD predictors, only exacerbation history remained a significant predictor of cognitive scores. Conclusions: The number of exacerbation events in a year may be used as a predictor of cognitive impairment in patients with COPD. Key words: cognitive function, chronic obstructive pulmonary disease, exacerbation, Mini Mental State Examination. Abbreviations: BMI, body mass index; CAT, COPD Assessment Test; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; DV, dependent variables; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; GOLD, Global Correspondence: Nart Bedin Atalay, TOBB Ekonomi ve Teknoloji Üniversitesi, Psikoloji Bölümü, Ankara, Turkey. Email: [email protected] Received 22 December 2013; invited to revise 13 February 2014; revised 1 April 2014; accepted 16 April 2014 (Associate Editor: Bob Hancox). Article first published online: 17 June 2014 © 2014 Asian Pacific Society of Respirology
SUMMARY AT A GLANCE We assessed the clinical features predictive of cognitive impairment in patients with COPD. We recruited 119 mild to severe COPD patients. After controlling for non-COPD predictors, only exacerbation history remained a significant predictor of cognitive scores. Exacerbations may be used as a predictor of cognitive impairment in patients with COPD.
Initiative for Chronic Obstructive Lung Disease; MMSE, Mini Mental State Examination; mMRC, modified British Medical Research Council; non-COPD, not related with COPD; OSAS, obstructive sleep apnoea syndrome.
INTRODUCTION Chronic obstructive pulmonary disease (COPD) is a heterogenic illness with pulmonary and extrapulmonary manifestations characterized by chronic airflow limitation. Until recently, the primary diagnosis and evaluation criteria for COPD were the presence and severity of chronic airflow limitation with forced expiratory volume in 1 s (FEV1).1 FEV1 has been documented to be an unreliable measure for assessing difficulties with breathlessness, limitations in physical activity and impairments of health.2 Beginning with the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD), disease impact and exacerbation risk have been considered in the treatment of COPD. Disease impact is assessed by using the COPD Assessment Test (CAT) or the modified British Medical Research Council (mMRC) dyspnoea scale. Exacerbation risk is suggested to be assessed via airflow limitation or exacerbation history.3 Patient-centred and individualized approaches in managing COPD is becoming more common, and comorbidities are getting more focus in the guidelines.4 Despite being associated with decreased daily living activities and difficulty complying with COPD Respirology (2014) 19, 873–880 doi: 10.1111/resp.12333
874 treatments, impaired cognitive function is a comorbidity that is often underestimated.5,6 Therefore, cognitive function should also be taken into account when developing a treatment plan. Cognitive impairment in COPD has been observed in both hypoxemic and non-hypoxemic patients. Furthermore, magnetic resonance imaging has shown cerebral hypoperfusion associated with cognitive dysfunction in these patients.7,8 However, the relationship between cognitive dysfunction and severity of COPD is still unclear owing to inconsistent results.5,6 To our knowledge, the association between different cognitive functions and exacerbation history, and CAT and mMRC scores has not yet been studied. Here, we used a broad array of standardized neuropsychological tests to assess general cognitive impairment and cognitive functions in the domains of attention, memory, psychomotor coordination and language. Our aims were to investigate the relationship between cognitive function and GOLD 2011 categories, to assess the clinical features that may be predictive of cognitive impairment in patients with COPD after controlling for non-COPD covariates and to determine whether a specific pattern of dysfunction exists among GOLD 2011 categories.
METHODS Participants and procedures Participants were consecutive patients with COPD who had been followed up regularly with 3-month intervals at least for a year in the Department of Chest Diseases, Selcuk University, Faculty of Medicine. All patients were at least 40 years old and had a smoking history of at least 10 pack-years. COPD was diagnosed according to internationally recognized guidelines using clinical history, symptoms and a postbronchodilator ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) of less than 0.70. Severity of airflow limitation was classified by their predictive FEV1 values as follows: mild (FEV1 ≥ 80%), moderate (50% ≤ FEV1 < 80%), severe (30% ≤ FEV1 < 50%) and very severe (FEV1 < 30%).3,9 Patients were grouped into four categories as proposed by GOLD 2011: A, low risk, fewer symptoms; B, low risk, more symptoms; C, high risk, fewer symptoms; D, high risk, more symptoms. In this categorisation, the cut-off points for symptoms and risks were chosen according to GOLD 2011 (for the category of symptoms, CAT ≥10; for the category of risks, exacerbations in previous year ≥2 and/or GOLD classification of airflow limitation ≥3). All patients were in a stable phase of the disease at the time of cognitive tests and none had experienced an exacerbation within the previous 6 weeks. During outpatient visits, all patients were assessed and mild to severe exacerbations recorded. COPD exacerbations were classified with reference to The American Thoracic Society/European Respiratory Society Task Force recommendations. No patients were hypoxemic and oxygen saturation over 90% was warranted via pulse oxymetry before neurophysiological Respirology (2014) 19, 873–880
B Tulek et al.
tests. Detailed explanation of procedure, health assessment and exclusion criteria are presented in Appendix S1 (see supporting information available online). The study was approved by the Ethics Committee of Clinical Research, Selcuk University, Faculty of Medicine. Written informed consent was obtained from all participants before the study.
Neuropsychological tests Standardized neuropsychological tests, which were already adapted to Turkish language, were conducted. Tests included MMSE (Mini Mental State Examination).10,11 Trail making A and B,12 clock drawing,13,14 forward and backward digit span tests, Brown–Peterson Test,15 verbal fluency test16 and Geriatric Depression Scale17 (see Appendix S2 in the supporting information available online for a detailed description). Statistical analysis Group differences were compared with one-way analyses of variance (ANOVAs) for normally distributed dependent variables (DVs), with Kruskal–Wallis and Mann–Whitney U-tests for non-normal DVs, and with chi-square tests for categorical variables. Total cognitive z was obtained by the addition of z values for each participant for each DV. The higher the score the better the cognitive function of the participant. Missing DV values were estimated with means. Level of significance was set to P < 0.05. Bonferroni correction of P-values was used for multiple comparisons. Sequential regression analyses were conducted to examine effects of exacerbations, FEV1 and C-reactive protein (CRP) on neuropsychological scores after controlling for the following non-COPD predictors of cognitive functions: age, education (last degree awarded), smoking (pack/years), body mass index (BMI), geriatric depression score, hypertension, diabetes and coronary heart disease. In the first step of sequential regression, independent variables were the non-COPD predictors. In the second step, exacerbation history (0–1 vs ≥2), or FEV1 (median split, 3.27 mg/L) was added to the separate regression models. Multivariate outliers were controlled with Mahalanobis distances.
RESULTS One hundred and nineteen patients completed the study. Demographic data, clinical parameters and number of patients in GOLD 2011 groups (classified by CAT) are shown in Table 1. Mean age was 59.5 years and patients were 97.5% male. Severity of airflow limitation ranged from mild to very severe. Most patients fell into either GOLD 2011 category D (n = 40, 33.6%) or category A (n = 37, 31.1%), followed by categories B (n = 28, 23.5%) and C (n = 14, 11.8%). We compared total cognitive z scores among patients with GOLD 2011 categories (Fig. 1) and found a significant difference between them (P < 0.001). Post-hoc Tukey’s analysis showed significant © 2014 Asian Pacific Society of Respirology
875
Cognitive function in COPD and GOLD 2011 Table 1 Demographic and clinical characteristics of patients with COPD Subjects Gender, M Age, years Smoking, packs/year BMI, kg/m2 Education, years Geriatric depression score GOLD 2011 phenotypes A B C D FEV1 ≥80% 50%–80% 50%–30%
ORIGINAL ARTICLE
Cognitive function in chronic obstructive pulmonary disease: Relationship to global initiative for chronic obstructive lung disease 2011 categories BAYKAL TULEK,1 NART BEDIN ATALAY,2 GULFEM YILDIRIM,1 FIKRET KANAT1 AND MECIT SÜERDEM1 1
Department of Chest Diseases, Faculty of Medicine, Selcuk University, Konya and 2Department of Psychology, TOBB University of Economics & Technology, Ankara, Turkey
ABSTRACT Background and objective: Recently, comorbidities such as impaired cognitive function have been attracting more focus when considering the management of chronic obstructive pulmonary disease (COPD). Here we investigated the relationship between cognitive function and the categories given in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in 2011. Specifically, after controlling for non-COPD covariates, we assessed the clinical features that may be predictive of cognitive impairment in patients with COPD. Methods: We recruited 119 stable patients with mild to very severe COPD. We administered a broad array of standardized neuropsychological tests that assessed cognitive functions in the domains of attention, memory, psychomotor coordination and language. Results: Cognitive scores were significantly different between patients falling within GOLD 2011 categories. Scores were lower in patients with high future risk compared with low future risk. In parallel, there were significant differences in cognitive function between COPD patient subgroups when patients were grouped according to the forced expiratory volume in 1 s, exacerbation history and C-reactive protein levels. After controlling for non-COPD predictors, only exacerbation history remained a significant predictor of cognitive scores. Conclusions: The number of exacerbation events in a year may be used as a predictor of cognitive impairment in patients with COPD. Key words: cognitive function, chronic obstructive pulmonary disease, exacerbation, Mini Mental State Examination. Abbreviations: BMI, body mass index; CAT, COPD Assessment Test; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; DV, dependent variables; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; GOLD, Global Correspondence: Nart Bedin Atalay, TOBB Ekonomi ve Teknoloji Üniversitesi, Psikoloji Bölümü, Ankara, Turkey. Email: [email protected] Received 22 December 2013; invited to revise 13 February 2014; revised 1 April 2014; accepted 16 April 2014 (Associate Editor: Bob Hancox). Article first published online: 17 June 2014 © 2014 Asian Pacific Society of Respirology
SUMMARY AT A GLANCE We assessed the clinical features predictive of cognitive impairment in patients with COPD. We recruited 119 mild to severe COPD patients. After controlling for non-COPD predictors, only exacerbation history remained a significant predictor of cognitive scores. Exacerbations may be used as a predictor of cognitive impairment in patients with COPD.
Initiative for Chronic Obstructive Lung Disease; MMSE, Mini Mental State Examination; mMRC, modified British Medical Research Council; non-COPD, not related with COPD; OSAS, obstructive sleep apnoea syndrome.
INTRODUCTION Chronic obstructive pulmonary disease (COPD) is a heterogenic illness with pulmonary and extrapulmonary manifestations characterized by chronic airflow limitation. Until recently, the primary diagnosis and evaluation criteria for COPD were the presence and severity of chronic airflow limitation with forced expiratory volume in 1 s (FEV1).1 FEV1 has been documented to be an unreliable measure for assessing difficulties with breathlessness, limitations in physical activity and impairments of health.2 Beginning with the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD), disease impact and exacerbation risk have been considered in the treatment of COPD. Disease impact is assessed by using the COPD Assessment Test (CAT) or the modified British Medical Research Council (mMRC) dyspnoea scale. Exacerbation risk is suggested to be assessed via airflow limitation or exacerbation history.3 Patient-centred and individualized approaches in managing COPD is becoming more common, and comorbidities are getting more focus in the guidelines.4 Despite being associated with decreased daily living activities and difficulty complying with COPD Respirology (2014) 19, 873–880 doi: 10.1111/resp.12333
874 treatments, impaired cognitive function is a comorbidity that is often underestimated.5,6 Therefore, cognitive function should also be taken into account when developing a treatment plan. Cognitive impairment in COPD has been observed in both hypoxemic and non-hypoxemic patients. Furthermore, magnetic resonance imaging has shown cerebral hypoperfusion associated with cognitive dysfunction in these patients.7,8 However, the relationship between cognitive dysfunction and severity of COPD is still unclear owing to inconsistent results.5,6 To our knowledge, the association between different cognitive functions and exacerbation history, and CAT and mMRC scores has not yet been studied. Here, we used a broad array of standardized neuropsychological tests to assess general cognitive impairment and cognitive functions in the domains of attention, memory, psychomotor coordination and language. Our aims were to investigate the relationship between cognitive function and GOLD 2011 categories, to assess the clinical features that may be predictive of cognitive impairment in patients with COPD after controlling for non-COPD covariates and to determine whether a specific pattern of dysfunction exists among GOLD 2011 categories.
METHODS Participants and procedures Participants were consecutive patients with COPD who had been followed up regularly with 3-month intervals at least for a year in the Department of Chest Diseases, Selcuk University, Faculty of Medicine. All patients were at least 40 years old and had a smoking history of at least 10 pack-years. COPD was diagnosed according to internationally recognized guidelines using clinical history, symptoms and a postbronchodilator ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) of less than 0.70. Severity of airflow limitation was classified by their predictive FEV1 values as follows: mild (FEV1 ≥ 80%), moderate (50% ≤ FEV1 < 80%), severe (30% ≤ FEV1 < 50%) and very severe (FEV1 < 30%).3,9 Patients were grouped into four categories as proposed by GOLD 2011: A, low risk, fewer symptoms; B, low risk, more symptoms; C, high risk, fewer symptoms; D, high risk, more symptoms. In this categorisation, the cut-off points for symptoms and risks were chosen according to GOLD 2011 (for the category of symptoms, CAT ≥10; for the category of risks, exacerbations in previous year ≥2 and/or GOLD classification of airflow limitation ≥3). All patients were in a stable phase of the disease at the time of cognitive tests and none had experienced an exacerbation within the previous 6 weeks. During outpatient visits, all patients were assessed and mild to severe exacerbations recorded. COPD exacerbations were classified with reference to The American Thoracic Society/European Respiratory Society Task Force recommendations. No patients were hypoxemic and oxygen saturation over 90% was warranted via pulse oxymetry before neurophysiological Respirology (2014) 19, 873–880
B Tulek et al.
tests. Detailed explanation of procedure, health assessment and exclusion criteria are presented in Appendix S1 (see supporting information available online). The study was approved by the Ethics Committee of Clinical Research, Selcuk University, Faculty of Medicine. Written informed consent was obtained from all participants before the study.
Neuropsychological tests Standardized neuropsychological tests, which were already adapted to Turkish language, were conducted. Tests included MMSE (Mini Mental State Examination).10,11 Trail making A and B,12 clock drawing,13,14 forward and backward digit span tests, Brown–Peterson Test,15 verbal fluency test16 and Geriatric Depression Scale17 (see Appendix S2 in the supporting information available online for a detailed description). Statistical analysis Group differences were compared with one-way analyses of variance (ANOVAs) for normally distributed dependent variables (DVs), with Kruskal–Wallis and Mann–Whitney U-tests for non-normal DVs, and with chi-square tests for categorical variables. Total cognitive z was obtained by the addition of z values for each participant for each DV. The higher the score the better the cognitive function of the participant. Missing DV values were estimated with means. Level of significance was set to P < 0.05. Bonferroni correction of P-values was used for multiple comparisons. Sequential regression analyses were conducted to examine effects of exacerbations, FEV1 and C-reactive protein (CRP) on neuropsychological scores after controlling for the following non-COPD predictors of cognitive functions: age, education (last degree awarded), smoking (pack/years), body mass index (BMI), geriatric depression score, hypertension, diabetes and coronary heart disease. In the first step of sequential regression, independent variables were the non-COPD predictors. In the second step, exacerbation history (0–1 vs ≥2), or FEV1 (median split, 3.27 mg/L) was added to the separate regression models. Multivariate outliers were controlled with Mahalanobis distances.
RESULTS One hundred and nineteen patients completed the study. Demographic data, clinical parameters and number of patients in GOLD 2011 groups (classified by CAT) are shown in Table 1. Mean age was 59.5 years and patients were 97.5% male. Severity of airflow limitation ranged from mild to very severe. Most patients fell into either GOLD 2011 category D (n = 40, 33.6%) or category A (n = 37, 31.1%), followed by categories B (n = 28, 23.5%) and C (n = 14, 11.8%). We compared total cognitive z scores among patients with GOLD 2011 categories (Fig. 1) and found a significant difference between them (P < 0.001). Post-hoc Tukey’s analysis showed significant © 2014 Asian Pacific Society of Respirology
875
Cognitive function in COPD and GOLD 2011 Table 1 Demographic and clinical characteristics of patients with COPD Subjects Gender, M Age, years Smoking, packs/year BMI, kg/m2 Education, years Geriatric depression score GOLD 2011 phenotypes A B C D FEV1 ≥80% 50%–80% 50%–30%
