Dement Geriatr Cogn Disord 2014;38:65–78 DOI: 10.1159/000357454 Accepted: November 11, 2013 Published online: March 1, 2014
© 2014 S. Karger AG, Basel 1420–8008/14/0382–0065$39.50/0 www.karger.com/dem
Original Research Article
Mild Cognitive Impairment with Associated Inflammatory and Cortisol Alterations as Independent Risk Factor for Postoperative Delirium Jakub Kazmierski a Andrzej Banys b Joanna Latek e Julius Bourke f Ryszard Jaszewski c Tomasz Sobow d Iwona Kloszewska a a
Department of Old Age Psychiatry and Psychotic Disorders, b Department of Anaesthesiology and Intensive Cardiologic Care, 1st Chair of Cardiology and Cardiac Surgery, c Department of Cardiac Surgery, 1st Chair of Cardiology and Cardiac Surgery, and d Department of Medical Psychology, Medical University of Lodz, and e Central Veterans Hospital, Lodz, Poland; f The Centre for Psychiatry at The Wolfson Institute for Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
Key Words Coronary artery bypass graft surgery · Cardiac surgery · Cobalamin · Cortisol · Cytokines · Homocysteine · Mild cognitive impairment
Jakub Kazmierski, MD, PhD Department of Old Age Psychiatry and Psychotic Disorders Medical University of Lodz, Czechoslowacka 8/10 PL–92-216 Lodz (Poland) E-Mail jakub.kazmierski @ umed.lodz.pl
Downloaded by: Universitätsbibliothek Düsseldorf 134.99.34.168 - 3/16/2014 10:49:30 AM
Abstract Aims: The present study aimed to determine the impact of mild cognitive impairment (MCI) on the development of postoperative delirium and, secondly, to assess the association between MCI and raised perioperative cortisol, cytokine, cobalamin and homocysteine levels. Methods: The study recruited 113 consecutive adult patients scheduled for cardiac surgery with cardiopulmonary bypass. The patients were examined preoperatively with the Montreal Cognitive Assessment and Trail Making Test. A diagnosis of MCI was established based upon the criteria of the National Institute on Aging and Alzheimer’s Association. Patients were screened for delirium within the first 5 days postoperatively. Results: MCI was diagnosed in 24.8% of the patients, whereas the frequency of delirium was 36%. A multivariate analysis demonstrated that individuals with MCI were at a significantly higher risk of postoperative delirium (OR = 6.33, p = 0.002). Preoperative cortisol, postoperative cortisol and IL-2 plasma levels were higher in the MCI group as compared to non-MCI subjects. Conclusion: MCI is associated with a higher risk of postoperative delirium. Perioperative cortisol and inflammatory alterations observed in MCI may provide a physiological explanation for this increased © 2014 S. Karger AG, Basel risk.
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Dement Geriatr Cogn Disord 2014;38:65–78 DOI: 10.1159/000357454
© 2014 S. Karger AG, Basel www.karger.com/dem
Kazmierski et al.: Mild Cognitive Impairment with Associated Inflammatory and Cortisol Alterations as Independent Risk Factor for Postoperative Delirium
Delirium is a neuropsychiatric syndrome of acute onset and with a fluctuating course, which is characterized by disturbance of consciousness with impaired attention and altered cognition. It is recognized as a complication of dementia (delirium superimposed on dementia) or as a consequence of a poor general medical condition [1]. Delirium may develop after major surgery and is particularly frequent among cardiac surgery patients (up to 50% of individuals) [2, 3]. The development of this cognitive syndrome results in higher mortality and morbidity rates, increases duration of admission and overall cost of hospitalization and is a risk factor of dementia and chronic institutionalization [4–6]. A number of studies have investigated risk factors for postoperative delirium, but findings have been heterogeneous. To date, the most consistently reported independent associations with delirium in studies of cardiac surgery include older age, preoperative dementia, nonclassified preexisting cognitive impairment (PreCI; usually both dementia and milder forms of cognitive impairment) and major depressive disorder (MDD) [7–10]. The other well-established risk factors of delirium include medical conditions such as dehydration, malnutrition, electrolyte or metabolic abnormalities, hypoglycemia, hypoxia, infection, hepatic impairment, renal impairment, cardiac ischemia, multiple medications and alcohol abuse [5, 11–14]. However, the relevance of mild cognitive impairment (MCI) in the development of delirium has not been elucidated. MCI is a heterogeneous entity in relation to etiology, clinical picture and prognosis [15, 16]. The concept of MCI as a transitional state between normal aging and Alzheimer’s disease (AD) has recently been extensively investigated [17–19]. According to prior studies, subjects with MCI convert to dementia at a rate of approximately 12% per year, compared to 1–2% for a cognitively normal population at the same age [17]. However, prognosis depends on the subtype of MCI that is diagnosed [16]. The most common form of this condition, especially in memory disorder clinics, is amnestic MCI (aMCI) which carries with it a higher risk for the development of AD [20]. In population samples of elderly patients with chronic medical conditions (hypertension, coronary artery disease and heart failure), nonamnestic MCI (naMCI) is frequently diagnosed [18]. Reports of MCI remission or improvement in population samples vary widely between 6 and 53% [19]. Controversies remain as to whether MCI is a preclinical state of dementia or a separate clinical entity. Recent studies confirm that cognitive impairment is common among elderly patients undergoing major surgery including cardiac interventions [3, 5, 8, 9, 21]. Depending on the diagnostic measures employed, the prevalence of cognitive disturbances ranges from 17 to 45% [3, 5, 8, 9, 21]. In most studies, patients were screened for cognitive impairment by the Mini-Mental State Examination (MMSE) [22]. The MMSE is a commonly used, short and easily applied measure. However, it is characterized by a low sensitivity for milder forms of cognitive impairment [23]. Dementia and unspecified cognitive disturbances (usually diagnosed on the basis of the MMSE with a cutoff score of
© 2014 S. Karger AG, Basel 1420–8008/14/0382–0065$39.50/0 www.karger.com/dem
Original Research Article
Mild Cognitive Impairment with Associated Inflammatory and Cortisol Alterations as Independent Risk Factor for Postoperative Delirium Jakub Kazmierski a Andrzej Banys b Joanna Latek e Julius Bourke f Ryszard Jaszewski c Tomasz Sobow d Iwona Kloszewska a a
Department of Old Age Psychiatry and Psychotic Disorders, b Department of Anaesthesiology and Intensive Cardiologic Care, 1st Chair of Cardiology and Cardiac Surgery, c Department of Cardiac Surgery, 1st Chair of Cardiology and Cardiac Surgery, and d Department of Medical Psychology, Medical University of Lodz, and e Central Veterans Hospital, Lodz, Poland; f The Centre for Psychiatry at The Wolfson Institute for Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
Key Words Coronary artery bypass graft surgery · Cardiac surgery · Cobalamin · Cortisol · Cytokines · Homocysteine · Mild cognitive impairment
Jakub Kazmierski, MD, PhD Department of Old Age Psychiatry and Psychotic Disorders Medical University of Lodz, Czechoslowacka 8/10 PL–92-216 Lodz (Poland) E-Mail jakub.kazmierski @ umed.lodz.pl
Downloaded by: Universitätsbibliothek Düsseldorf 134.99.34.168 - 3/16/2014 10:49:30 AM
Abstract Aims: The present study aimed to determine the impact of mild cognitive impairment (MCI) on the development of postoperative delirium and, secondly, to assess the association between MCI and raised perioperative cortisol, cytokine, cobalamin and homocysteine levels. Methods: The study recruited 113 consecutive adult patients scheduled for cardiac surgery with cardiopulmonary bypass. The patients were examined preoperatively with the Montreal Cognitive Assessment and Trail Making Test. A diagnosis of MCI was established based upon the criteria of the National Institute on Aging and Alzheimer’s Association. Patients were screened for delirium within the first 5 days postoperatively. Results: MCI was diagnosed in 24.8% of the patients, whereas the frequency of delirium was 36%. A multivariate analysis demonstrated that individuals with MCI were at a significantly higher risk of postoperative delirium (OR = 6.33, p = 0.002). Preoperative cortisol, postoperative cortisol and IL-2 plasma levels were higher in the MCI group as compared to non-MCI subjects. Conclusion: MCI is associated with a higher risk of postoperative delirium. Perioperative cortisol and inflammatory alterations observed in MCI may provide a physiological explanation for this increased © 2014 S. Karger AG, Basel risk.
66
Dement Geriatr Cogn Disord 2014;38:65–78 DOI: 10.1159/000357454
© 2014 S. Karger AG, Basel www.karger.com/dem
Kazmierski et al.: Mild Cognitive Impairment with Associated Inflammatory and Cortisol Alterations as Independent Risk Factor for Postoperative Delirium
Delirium is a neuropsychiatric syndrome of acute onset and with a fluctuating course, which is characterized by disturbance of consciousness with impaired attention and altered cognition. It is recognized as a complication of dementia (delirium superimposed on dementia) or as a consequence of a poor general medical condition [1]. Delirium may develop after major surgery and is particularly frequent among cardiac surgery patients (up to 50% of individuals) [2, 3]. The development of this cognitive syndrome results in higher mortality and morbidity rates, increases duration of admission and overall cost of hospitalization and is a risk factor of dementia and chronic institutionalization [4–6]. A number of studies have investigated risk factors for postoperative delirium, but findings have been heterogeneous. To date, the most consistently reported independent associations with delirium in studies of cardiac surgery include older age, preoperative dementia, nonclassified preexisting cognitive impairment (PreCI; usually both dementia and milder forms of cognitive impairment) and major depressive disorder (MDD) [7–10]. The other well-established risk factors of delirium include medical conditions such as dehydration, malnutrition, electrolyte or metabolic abnormalities, hypoglycemia, hypoxia, infection, hepatic impairment, renal impairment, cardiac ischemia, multiple medications and alcohol abuse [5, 11–14]. However, the relevance of mild cognitive impairment (MCI) in the development of delirium has not been elucidated. MCI is a heterogeneous entity in relation to etiology, clinical picture and prognosis [15, 16]. The concept of MCI as a transitional state between normal aging and Alzheimer’s disease (AD) has recently been extensively investigated [17–19]. According to prior studies, subjects with MCI convert to dementia at a rate of approximately 12% per year, compared to 1–2% for a cognitively normal population at the same age [17]. However, prognosis depends on the subtype of MCI that is diagnosed [16]. The most common form of this condition, especially in memory disorder clinics, is amnestic MCI (aMCI) which carries with it a higher risk for the development of AD [20]. In population samples of elderly patients with chronic medical conditions (hypertension, coronary artery disease and heart failure), nonamnestic MCI (naMCI) is frequently diagnosed [18]. Reports of MCI remission or improvement in population samples vary widely between 6 and 53% [19]. Controversies remain as to whether MCI is a preclinical state of dementia or a separate clinical entity. Recent studies confirm that cognitive impairment is common among elderly patients undergoing major surgery including cardiac interventions [3, 5, 8, 9, 21]. Depending on the diagnostic measures employed, the prevalence of cognitive disturbances ranges from 17 to 45% [3, 5, 8, 9, 21]. In most studies, patients were screened for cognitive impairment by the Mini-Mental State Examination (MMSE) [22]. The MMSE is a commonly used, short and easily applied measure. However, it is characterized by a low sensitivity for milder forms of cognitive impairment [23]. Dementia and unspecified cognitive disturbances (usually diagnosed on the basis of the MMSE with a cutoff score of
