The impacts of cognitive impairment on acute exacerbations of chronic obstructive pulmonary disease Dr. Lo Iek Long Department of Respiratory Medicine C.H.C.S.J.
Chronic Obstructive Pulmonary Disease (COPD) Normal Airway Inflammation Parenchymal Destruction
Airflow limitation FEV1/FVC < 70% Without bronchodilator response
Bronchodilators & Inhaled steroid
GOLD guidelines Pulmonary effects Extra-pulmonary effects Multiple-component Co-morbidities From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2010. Available from: http://www.goldcopd.org.
Complex chronic co-morbidities of COPD European Respiratory Journal 2008
COPD and cognitive impairment 42% of COPD patients with hypoxemia had cognitive dysfunction [1]. COPD may lead to the development of cognitive impairment [2]. There is little data regarding the impacts of cognitive impairment on COPD outcomes. 1. Grant I, Heaton RK, McSweeny AJ, et al. Neuropsychologic findings in hypoxemic chronic obstructive pulmonary disease. Arch Intern Med 1982;142:1470-6. 2. Hung WW, Wisnivesky JP, Siu AL, et al. Cognitive decline among patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2009;180:134-137.
Purpose To investigate the impacts of cognitive impairment on 1) Frequency of COPD exacerbations 2) Hospital service utilization 3) Quality of life (QoL) in Chinese elderly COPD patients.
Methodology Design: 6-month prospective study Inclusion criteria: 60 years Chinese Lung function confirmed COPD Exclusion criteria: Other active lung disease Malignancy within 5 years Advanced stage chronic diseases Difficulty in communication or language barrier
Baseline assessment Basic (age, gender, smoking status, education, living condition) Co-morbidity (HTN, DM, IHD, CHF, CVA, etc) COPD Severity (FEV1, GOLD stage, NYHA dyspnea scale, home oxygen usage) Medication usage (SABA, SAMA, LABA, LAMA, ICS, theophylline) Compliance to medications (good/fair/poor) Inhaler technique (optimal vs suboptimal) Anxiety and depression (Hospital Anxiety and Depression Score, HADS)
HADS and SF-12
Mini Mental State Examination (MMSE) Education-adjusted MMSE cutoff points 0 year MMSE 18 1 to 2 years MMSE 20 3 years MMSE 22 Categorized the COPD subjects into: Normal cognition Cognitive impairment
Follow-up for at 3- and 6-month Outcome Measures frequency of exacerbation ER visit Hospital admission QoL - physical and mental component (SF-12)
Informed consent
IRB approval
Results
Screening and recruitment From Dec 1, 2009 to May 31, 2010
Results The mean age of these subjects was 74.7 ± 7.8 years (range 60-90 years). 88.6% patients were male. 82.6% live with support person, 4.5% live in OAH, and 12.9% live alone. Mean education 5.6 ± 4.6 years. Mean time spent outdoors was 3.4 ± 2.5 hours.
Smoking status Among the smokers, mean smoking history: 57.2 ± 29.2 pack-years.
Co-morbidities
COPD severity Mean FEV1 was 49.3 ± 17.4 % predicted
Medications Short-acting beta-agonist 62.9% Short-acting anti-cholinergic 56.8% Long-acting beta-agonist 59.8% Long-acting anti-cholinergic 46.2% Inhaled corticosteroid 75.0% Theophylline (Euphylong) 56.1%
Neuro-phycological aspects 42.4% patients had cognitive impairment Mean MMSE score was 22.2 ± 5.4 38.6% patients had anxiety Mean HADS Anxiety score was 2.4 ± 2.8 56.8% patients had depressive mood Mean HADS Depression score was 6.7 ± 3.8
Factors associated with cognitive impairment Variables Normal cognition (n=76) Cognitive impairment (n=56) P value Age 73.2 ± 7.6 76.8 ± 7.6 0.007 Female 5 (6.6%) 10 (17.9%) 0.044 FEV1 % predicted 49.6 ± 17.6 48.9 ± 17.3 0.82 NYHA Dyspnea scale 0.055 1 17 (22.4%) 7 (12.5%) 2 24 (31.6%) 9 (16.1%) 3 14 (18.4%) 14 (25.0%) 4 9 (11.8%) 14 (25.0%) 5 12 (15.8%) 12 (21.4%)
Factors associated with cognitive impairment Variables Type of medication Normal cognition (n=76) Cognitive impairment (n=56) P value SABA 46 (60.5%) 37 (66.1%) 0.515 SAMA 44 (57.9%) 31 (55.4%) 0.771 LABA 42 (55.3%) 37 (66.1%) 0.211 LAMA 36 (47.4%) 25 (44.6%) 0.756 ICS 54 (71.1%) 45 (80.4%) 0.222 Theophylline 37 (48.7%) 37 (66.1%) 0.047
Factors associated with cognitive impairment Variables Normal cognition (n=76) Cognitive impairment (n=56) P value Compliance to medication 0.046 Poor Fair Good 1 (1.3%) 7 (9.2%) 68 (89.5%) 5 (8.9%) 9 (16.1%) 42 (75.0%) Inhaler techniques 0.047 Suboptimal 37 (48.7%) 37 (66.1%) Optimal 39 (51.3%) 19 (33.9%)
Factors associated with cognitive impairment Variables Normal cognition (n=76) Cognitive impairment (n=56) P value MMSE 25.9 ± 2.5 16.9 ± 3.5 <0.01 Anxiety score 2.4 ± 2.6 2.5 ± 2.9 0.73 Depression score 5.8 ± 3.3 7.9 ± 4.2 0.002 SF-12 PCS 39.1 ± 10.2 33.4 ± 10.1 0.002 SF-12 MCS 49.7 ± 9.1 47.6 ± 7.2 0.15
Cognitive impairment in COPD Compared to COPD subjects with normal cognition, subjects with cognitive impairment were: Older Higher proportion of females More theophylline usage Poorer compliance to medications Suboptimal inhaler technique Higher depression score Lower physical component of quality of life
Logistic regression analysis of independent factors associated with cognitive impairment in COPD Factors Odds Ratio (OR) 95% CI of OR P value Age years 1.06 1.004 1.11 0.036* Gender (female vs male) 4.31 1.17 15.8 0.028* Theophylline use 2.35 1.04 5.28 0.04* Depression score 1.11 0.996 1.24 0.06 PCS-12 0.95 0.91 0.99 0.016*
6-month follow-up data 6-month outcomes Normal cognition (n=76) Cognitive impairment (n=56) P value No. of exacerbations 2.40± 2.20 3.50± 2.05 0.004* No. of ER visits 1.15± 1.70 2.07± 1.88 0.004* No. of Hospitalizations 0.24± 0.49 0.71± 0.68 <0.001*
Discussion
Cognitive impairment and COPD The prevalence of cognitive impairment was 42.2% among elderly COPD. CI was independently associated with old age and female gender among COPD patients. It has been reported that that severe COPD was an independent risk factor for cognitive decline. We suggested the clinicians should screen their COPD patients for cognitive impairment. Hung WW, Wisnivesky JP, Siu AL, et al. Cognitive decline among patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2009;180:134-137.
When cognitive impairment was found Identify the potentially treatable causes. Differentiate between Mild Cognitive Impairment (MCI) and Dementia. Manage cognitive impairment in a proactive manner, such as providing cholinesterase inhibitors, cognitive rehabilitation, and instructions to the caregivers. Clare L, Woods B. Cognitive rehabilitation and cognitive training for early-stage Alzheimer's disease and vascular dementia. Cochrane Database of Systematic Reviews 2003; 4: CD003260. Angevaren M, Aufdemkampe G, Verhaar HJ, et al. Physical activity and enhanced fitness to improve cognitive function in older people without known cognitive impairment. Cochrane Database Syst Rev 2008; 2: CD005381.
COPD and cognitive impairment COPD Cognitive impairment
Cognitive impairment and depressive mood and quality of life COPD patients with cognitive impairment had higher depression scores than those without. We also found that COPD patients with cognitive impairment had lower physical component of QoL.
Cognitive impairment increases COPD exacerbations This was the first study showing cognitive impairment increased the risk of having COPD exacerbations, and related hospital service utilizations, after adjusting for other confounding factors including gender and age.
Possible explanations Cognitive impairment compliance Inhaler technique Theophylline Exacerbation Vestbo J, Anderson JA, Calverley P, et al. Adherence to inhaled therapy, mortality, and hospital admission in COPD. Thorax 2009;64:939 43. Lee TA, Schumock GT, Bartle B, et al. Mortality risk in patients receiving drug regimens with theophylline for chronic obstructive pulmonary disease. Pharmacotherapy 2009;29:1039 53.
Theophylline and exacerbations In a retrospective study involving 183,573 COPD patients, it showed that regimens including theophylline slightly increased the risk of COPD exacerbations and hospitalization. Therefore, the higher proportion of theophylline used among COPD patients with cognitive impairment may possibly lead to their higher risk of exacerbation. Lee TA, Schumock GT, Bartle B, et al. Mortality risk in patients receiving drug regimens with theophylline for chronic obstructive pulmonary disease. Pharmacotherapy 2009;29:1039 53.
Conclusions Cognitive impairment was common among elderly COPD patients Cognitive impairment was negatively associated with quality of life and mood. Cognitive impairment predicted the increased risk of having COPD exacerbations and related hospital service utilizations.
Acknowledgement Prof. Chu LW in Hong Kong University Dr. Cheong Tak Hong and doctors in CHCSJ Ms. Ng Pak Leng in CHCSJ
Limitations Firstly, the sample size of this study was small and all subjects were Chinese elderly patients from a single hospital in Macao. Selection bias was a possible issue. Secondly, we could not avoid the influence of weather and influenza endemics on the frequency of exacerbation as we had only the 6-month follow-up data.
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