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Anesth Analg 2007;104:1023-1028
© 2007 International Anesthesia Research Society
doi: 10.1213/01.ane.0000263285.03361.3a

CARDIOVASCULAR ANESTHESIA

Preexisting Cognitive Impairment in Patients Scheduled for Elective Coronary Artery Bypass Graft Surgery

Brendan S. Silbert, MB, BS, FANZCA*, David A. Scott, MB, BS, PhD, FANZCA*, Lisbeth A. Evered, BSc*, Matthew S. Lewis, BApp Sci (Hons), PhD*{dagger}, and Paul T. Maruff, PhD{dagger}

From the *Department of Anaesthesia, Centre for Anaesthesia and Cognitive Function, St. Vincent's Hospital; and {dagger}School of Psychological Science, La Trobe University, Melbourne, Australia.

Address correspondence to Brendan Silbert, MB, BS, FANZCA, Department of Anaesthesia, St. Vincent's Hospital, PO Box 2900, Fitzroy, Australia. Address e-mail to brendan.silbert{at}svhm.org.au.


   Abstract
Top
 Abstract
Introduction
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
BACKGROUND: An accurate assessment of the prevalence of cognitive impairment in patients scheduled for coronary artery bypass graft (CABG) surgery is necessary if valid assumptions regarding cognitive change are to be made. Such an assessment requires the use of a healthy control group free of cardiovascular disease.

METHODS: In a retrospective observational study, 349 patients scheduled for CABG surgery underwent neuropsychological testing. We compared the results with those from a group of 170 healthy controls without cardiovascular disease and containing more female patients who were matched for age and IQ score. Cognitive impairment was defined as test scores ≥2 sd less than the controls on two or more of the seven tests.

RESULTS: The CABG surgery patients performed significantly worse than the control group on all tests except the Grooved Pegboard test (nondominant). When analyzed by group, performance on the verbal learning test was the most impaired. Cognitive impairment was present in 122 (35%) of CABG surgery patients before their procedure. Prior myocardial infarction, age, and IQ were independent predictors of cognitive impairment.

CONCLUSIONS: Cognitive impairment is prevalent in patients presenting for CABG surgery. Impaired cognition before surgery must be considered when assessing the effects of CABG surgery on cognitive performance.


   Introduction
Top
 Abstract
 Introduction
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
There is now agreement that cardiovascular disease is associated with an increased risk of cognitive impairment in older individuals, even in the absence of neurodegenerative disease or clinical history of stroke (1). Epidemiological studies have found links between cognitive impairment and vascular risk factors, such as hypertension (2), diabetes (3), hypercholesterolemia (4), and peripheral vascular disease (5). These relationships are consistent with risk models for cerebrovascular disease, and stroke in particular, because of the marked similarity with the same associations of cardiovascular risk factors. In this context, cognitive impairment in older individuals with cardiovascular disease is considered to be an early marker of vascular pathology in the central nervous system.

Patients with severe cardiovascular disease often present for coronary artery bypass graft (CABG) surgery. There is sound evidence that this surgery may be followed by cognitive deterioration known as postoperative cognitive deficit (POCD) (6,7). However, given the poor cardiovascular health of individuals undergoing CABG surgery, and the known associations between cardiovascular disease and cognitive impairment, it is likely that cognitive impairment will be present in at least some individuals awaiting CABG surgery. This cognitive impairment likely reflects subclinical cerebral vascular disease. Surprisingly, despite the many studies which have focused on POCD, the issue of impaired cognition before surgery in this group of patients has received scant attention. Most studies have focused on either group or individual change in cognitive function after the operation compared with a preoperative baseline (8).

A suggestion that patients awaiting CABG surgery may be suffering from cognitive impairment was first made by Vingerhoets et al. (9) in an explorative study. While undertaking a study of POCD, Millar et al. (10) noted that 16% of patients performed poorly on the Stroop test, indicating impaired preoperative cognition. Hogue et al. (11) while studying only female subjects, and using a normal control group for comparison, showed that cognitive impairment was present in 45% of patients presenting for elective cardiac surgery. The use of normal controls to identify cognitive impairment is important because such cognitive impairment may be associated with the cardiovascular disease that brings these patients to surgery.

An accurate assessment of cognitive impairment in patients with coronary artery disease is important because such impairment may be associated with POCD (9,10). A high prevalence and magnitude of preoperative cognitive impairment (rather than the nature of the surgery) in cardiac surgery patients may account for the higher incidence of POCD compared with noncardiac patients.

To determine the prevalence, characteristics and magnitude of cognitive impairment in older individuals presenting for CABG surgery, we used neuropsychological test results from the AustraliaN Trial Investigating PostOperative cognitive Deficit, Early extubation and Survival (ANTIPODES) Trial (12) and compared the results with those from a group of healthy age-matched controls without cardiovascular disease.


   METHODS
Top
 Abstract
 Introduction
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Subjects
The study group comprised 350 patients enrolled in the ANTIPODES (12). Institutional Ethics Committee approval was granted and written informed consent was obtained from all patients. Eligible patients were aged 55 yr or older scheduled to undergo elective first-time CABG surgery. Exclusion criteria were the presence of poor ventricular function (ejection fraction <30%), associated major systemic illness, preexisting neurological disease (including stroke or dementia), or anticipated difficulty with neuropsychological assessment (e.g., English not the prime language, psychiatric illness). Neuropsychological assessment was undertaken before surgery, either at the preadmission clinic or the day before surgery.

One hundred seventy control participants were drawn from two previous studies. Ninety controls consisted of friends and family members of patients undergoing CABG surgery at one hospital (13), whereas the remaining 80 patients had responded to general advertisements for involvement in a study of healthy aging (14). All individuals underwent psychiatric and neurological assessment at entry to the study and a full medical history was taken to assess each person's health status. The exclusion criteria included a history of respiratory, circulatory or endocrine disease, personal or family history of psychiatric illness, head injury or substance abuse, mini mental status examination score <27 and English as not the primary language. The control participants completed the same neuropsychological test battery as the CABG surgery group.

Neuropsychological Testing
The neuropsychological tests used to assess the patients in this study were selected on the basis of their sensitivity to impairment in a range of cognitive domains in older people and were consistent with previously recommended criteria (15). The test battery administered to both study and control subjects, consisted of the CERAD Auditory Verbal Learning test, Digit Symbol Substitution test, Trail Making test parts A and B, Controlled Oral Word Association test and the Grooved Pegboard test (dominant and nondominant hands). The results are given as the number of correct answers or the time taken to complete the test. Intelligent quotient (IQ) was derived from the results of the National Adult Reading Test (NART) (16). All of these tests have been described elsewhere (12).

All neuropsychological assessments were conducted by trained assessors and were conducted under the supervision of a neuropsychologist (PM). Attempts were made to keep the environment comfortable and free of distractions by using a quiet interview room for testing. Control patients were also tested in a quiet room in the hospital.

The presence of anxiety, depression and fatigue may affect the performance of cognitive testing in preoperative patients, therefore visual analog scales were used to assess anxiety and depression at the time of testing in the CABG surgery patients (17). These are especially suitable for this situation because they offer simple, reliable, and valid techniques for measuring anxiety and depression while placing minimal demands on patients (18,19). Patients were asked to mark an ungraded line (10 cm in length) anchored by 0 and 100 at each end.

For each individual, performance on each of the classification tests was standardized to z-scores using the mean and sd from the control group. The signs of the standardized scores were adjusted for all measures so that negative scores indicated poorer performance.

We defined impairment for each test when the test score was ≥2 sd below the control mean for that test. Cognitive impairment was defined for each individual patient when impairment was present in two or more tests of the seven performance measures (10). Using binomial distributions and assuming the hypothesis is one-tailed, the probability of Type I error using this criterion is <5% (20,21). For patients who were unable to complete the full battery of seven tests, decline was defined as impairment in two or more tests of the number of tests actually completed. No patient completed fewer than two tests.

Statistics
Group comparisons were made using unpaired t-tests for continuous variables, Mann–Whitney U-test for ranked data, and {chi}2 or Fisher's exact test for dichotomous parameters. Effect size was calculated using Cohen's d (d is defined as the difference between two means divided by the pooled sd for those means) (22).

Multivariable logistic regression was used to determine independent associations with cognitive impairment for patient variables (Table 1) and visual analog scores. A P value of <0.2 on univariable regression was set for entry into multivariable regression. Tests were performed using STATA (Version 8.0 Stata Corporation, College Station, TX). A P value of <0.05 was taken to indicate statistical significance.


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  		Table 1. Patient Demographics and Medical History

 


   RESULTS
Top
 Abstract
 Introduction
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
For the control group the mean age (sd) was 68.5 (6.4) and IQ was 109 (11). The male-to-female ratio was 117/53. For the CABG surgery group, the patient characteristics including medical history and medications are shown in Table 1. There was a small loss of data as seen by the numbers in Table 1. There was no difference between the CABG surgery group and the control group in age or IQ. The male-to-female ratio for the CABG group was 270/79 and was greater than that of the control group (P = 0.04), but there was no significant difference in neuropsychological test scores between men and women for any test.

Three hundred forty-nine CABG surgery patients completed the neuropsychological assessment before surgery, although not all patients completed all seven tests (Table 2). All the controls completed all tests. There was no significant difference between the scores for men and women in the control group.


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  		Table 2. Neuropsychological Test Results for Coronary Artery Bypass Graft (CABG) Patients and Controls

 

Group mean scores on each of the neuropsychological measures for the CABG surgery group and the control group and effect size are shown in Table 2. The CABG surgery group performed significantly worse than the control group on all tests except the Grooved Pegboard test (nondominant) (the mean duration to complete this test in the CABG surgery group was only 0.3 s longer than the mean of the control group). In the CABG surgery group, verbal learning (CERAD Auditory Verbal Learning test) was the most impaired and the magnitude of this impairment was by convention large (23). Robust but moderate group differences were observed for measures of executive function (Controlled Oral Word Association test) and motor dexterity. Small but significant impairments in cognitive function were observed across all of the other measures with the exception of the measure of motor dexterity for the nondominant hand.

The mean ± sd for visual analog scores in the CABG surgery group were 25.4 ± 26.8 for depression, 48.4 ± 31.0 for anxiety and 38.5 ± 30.1 for fatigue. Among the controls, visual analog scores for depression and anxiety but not fatigue were recorded only for the 80 patients in the healthy aging study (14). The mean ± sd visual analog score for depression was 32.4 ± 23.3 and was statistically significantly higher than the CABG surgery group (P = 0.03) and for anxiety was 41.5 ± 30.5, which did not statistically differ from the CABG surgery group (P = 0.07). The number and percentage of impaired performances in each individual test is shown in Table 3. One hundred twenty-two of the CABG surgery group (35%) satisfied the criteria for cognitive impairment (impairment in ≥2 of the seven tests).


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  		Table 3. Impaired Performance in Neuropsychological Test Results

 

On the basis of univariable regression, previous myocardial infarction, age, IQ, and depression were assessed in the multivariable model. Multivariable logistic regression indicated that the presence of cognitive impairment was independently associated with a history of myocardial infarction, age, and lower IQ (Table 4) but no other clinical risk factors nor the total number of clinical risk factors.


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  		Table 4. Variables Independently Associated with Preexisting Cognitive Impairment

 


   DISCUSSION
Top
 Abstract
 Introduction
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Cognitive dysfunction after cardiac surgery has been the subject of many studies and reviews. The dominant focus of these reports has been on the short and long-term change in cognitive function after surgery from baseline. Many studies have attempted to identify the particular aspect of the operative process which leads to this change. In contrast, the preoperative cognitive status in this group of patients has been less well studied. If there is cognitive impairment before surgery, it may influence postoperative outcome and thus is an important issue.

Cognitive impairment in individuals at risk for cerebrovascular pathology, but who have not suffered clinical stroke, suggests the presence of a cognitive prodrome for vascular neurodegenerative disease. Patients presenting for CABG surgery are likely to include a large proportion of such patients because the same vascular pathology which has affected the coronary vessels may also have affected the cerebral vessels. A high prevalence of cognitive impairment in these patients preoperatively would distinguish them from other surgical groups, and could account for frequent incidence of POCD after CABG surgery. Furthermore, the presence of preoperative cognitive impairment may potentially provide an indication of "at risk" patients so that steps can be taken to minimize the likelihood of cognitive impairment arising.

To accurately assess preoperative cognitive status in patients presenting for CABG surgery, a control group without cardiovascular disease must be tested for cognition. Our control group matched for age and IQ (factors known to affect cognition) and although the gender ratio differed from the study group, gender was shown to have no effect on cognition. Many studies investigating cognitive change after surgery have not compared their study samples with a control group and consequently have not been able to accurately assess baseline cognitive function. Those studies that have attempted to quantify baseline function have limitations. The study by Vingerhoets et al. (9) for example included a small number of patients. Millar et al. (10) used only a single psychometric test of attention and concentration (Stroop Neuropsychological Screening Test). Hogue et al. (11) confined their study to women. While comparing the effects of on-pump and off-pump CABG surgery on cognition, Rankin et al. (24) noted impaired presurgical performance in nearly every cognitive domain, and Van Dijk et al. (25) noted poor performance in specific preoperative cognitive tests. In the present study we used a battery of standard neuropsychological tests and investigated performance on these in large groups of patients (349) and controls (170). Hence, the current study has provided reliable estimates of the prevalence, character and magnitude of cognitive impairment in the CABG surgery group.

The use of healthy controls without cardiovascular or other disease (e.g., hypertension, endocrine etc) is important to identify the association of cognitive impairment with cardiovascular disease because randomly selected age-matched control subjects in this population are likely to have a high rate of coexisting disease. It is essential that the control group be free of cardiovascular disease because this may be associated with cognitive impairment. This fact is reinforced when nonsurgical patients with cardiovascular disease have been used as controls for CABG surgery patients and no cognitive impairment has been demonstrated in the cardiac surgery group (26).

When considered at the level of the individual patient, cognitive impairment was classified in 35% of the pre-CABG patients using a criterion that was appropriately conservative. This rate of impairment is consistent with that observed in the one other study that conducted the same type of analysis where 45% of the female sample met similar criteria for cognitive impairment (11). In the current CABG surgery group, the best independent predictors of cognitive impairment were prior myocardial infarction, age, and IQ. Hogue et al. (11) also found that age and level of education (level of education correlates with IQ) and prior myocardial infarction were associated with cognitive impairment.

It is interesting to speculate why we did not observe an independent association between the total number of clinical risk factors for cardiovascular disease and cognitive status. In population studies, clinical risk factors are used as proxies for the presence of cardiovascular disease. In this study, all patients awaiting CABG surgery had been shown to have definitive cardiovascular disease, and thus the relevance of clinical risk factors may be less important in this group.

Interestingly, the impairment detected was not generalized across all neuropsychological measures. No impairment was found for motor function in the nondominant hand and the magnitude of impairment varied for the cognitive functions measured, with the most severe impairment occurring for verbal memory learning and executive function (COWAT) and the smallest for measures of complex attentional function. Despite the robust nature of the impairment in memory and executive function in the group, no individual patient showed impairment sufficient to warrant clinical investigation for dementia or stroke. The finding that impairment was greatest for higher cognitive functions, such as memory, and small or nonexistent for motor and simple attentional functions, suggests that this may reflect disruption to higher brain centers associated with integrative cognitive functions. Although there was no significant difference in anxiety scores between groups, the CABG surgery group reported statistically lower depression scores. While this is unusual (and unlikely to be of clinical significance), if depression were to exacerbate cognitive impairment, it would tend to make our estimate of cognitive impairment in the CABG surgery group more conservative than would otherwise be expected.

Establishing the baseline prevalence of cognitive impairment in patients presenting for CABG surgery is an important finding that has several implications. First, low baseline psychometric scores may greatly influence the findings after surgery, because subsequent decreases are harder to detect and furthermore subject to both regression to the mean (27) and floor effects (28). Second, there is the possibility that low baseline scores may lead to further cognitive dysfunction and thus be an important predictor of POCD (10). If this were the case, the identification of such patients would be important and, at the very least, allow risk stratification.

Population studies have repeatedly shown that the same clinical risk factors implicated in cardiovascular disease are associated with cognitive impairment and dementia. Thus, the Canadian Study of Health and Aging identified age, diabetes, hypertension and heart problems (29), the Cache County identified hypertension, obesity and diabetes (30), and the Rotterdam study identified increasing age, previous vascular events, and carotid and peripheral arterial disease (5). Given that these risk factors are markers of cardiovascular disease, it is not surprising that subjects with proven coronary artery disease have a frequent prevalence of cognitive impairment.

In conclusion, we have identified preexisting cognitive impairment in more than one-third of patients presenting for CABG surgery. The most severe impairment occurred for verbal memory learning. These findings may challenge the assumption that POCD relates directly to the effects of the surgical procedure and suggest that it be associated with poor preexisting cognition. In future, analysis of POCD should consider preexisting cognitive status.


   Footnotes
 
Accepted for publication January 23, 2007.

Supported by National Health and Medical Research Council, Australia (Project Grant No. 140510).

Reprints will not be available from the author.


   REFERENCES
Top
 Abstract
 Introduction
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press