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Ann Thorac Surg 2006;82:812-818
© 2006 The Society of Thoracic Surgeons

Original article: Cardiovascular

Cognitive Function in Candidates for Coronary Artery Bypass Graft Surgery

Christine S. Ernest, DPsycha,*, Barbara M. Murphy, PhDa, Marian U.C. Worcester, PhDa, Rosemary O. Higgins, GradDip BehHltha, Peter C. Elliott, PhDa, Alan J. Goble, MD, FRACPa, Michael R. Le Grande, MPHa, Natalie Genardini, DPsycha, James Tatoulis, MS, FRACSb

a Heart Research Centre, Melbourne, Australia
b Department of Cardiothoracic Surgery, The Royal Melbourne Hospital, Melbourne, Australia

Accepted for publication April 3, 2006.

* Address correspondence to Dr Ernest, Heart Research Centre, Box 2137 Post Office, The Royal Melbourne Hospital, Victoria 3050, Australia (Email: christine.ernest{at}heartresearchcentre.org).


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
BACKGROUND: While many studies have investigated cognitive impairments in patients after coronary artery bypass graft surgery, very few have closely evaluated presurgical cognitive functioning of bypass candidates.

METHODS: A battery of neuropsychologic tests was administered to a consecutive series of patients listed for bypass surgery (n = 109). Cognitive function of bypass candidates was compared with that of a healthy control group (n = 25) and published test norms.

RESULTS: Cognitive test scores in candidates for bypass were significantly lower than those of the control group on tests of attention, information processing speed, and verbal memory. Additionally, bypass candidates' cognitive test scores were significantly reduced compared with expected values derived from validated test norms, on all but one cognitive test.

CONCLUSIONS: Cognitive performances of candidates for bypass were significantly lower than those of a healthy control group and published cognitive test norms.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
Cognitive outcomes after coronary artery bypass graft surgery (CABGS) have been extensively investigated [1–5]. Generally postsurgical outcome is quantified in terms of decline in cognitive function from presurgery to postsurgery, using presurgical cognitive function as the baseline for each individual. Yet, to our knowledge, only three studies have focused on cognitive function prior to surgery [6–8]. In these studies, bypass candidates were found to have reduced performances in the domains of attention [6], psychomotor speed or manual dexterity [7, 8], verbal fluency [8], and verbal memory [7, 8]. Another study, conducted by Rosengart and colleagues [9] in candidates for CABGS as well as percutaneous coronary intervention, reported reduced performances in verbal fluency and memory prior to intervention.

These findings question the relevance of using presurgical cognitive function as a standard or benchmark to compare postbypass cognitive function in outcomes studies [2, 5]. Patients with cognitive impairment prebypass have been shown to be at a higher risk for developing postoperative cognitive impairment [6, 10]. At the same time, patients with extremely low presurgical cognitive test scores may not be able to demonstrate this decline on cognitive assessment due to a "floor effect" on cognitive tests [1, 2, 6, 7]. In bypass outcome studies, there has been considerable variation in reports of the incidence of postbypass cognitive decline, with this variation attributed to various factors including the definition of decline [11, 12]. Despite these issues, the use of presurgical cognitive assessments to define postbypass cognitive decline has been widely accepted. Therefore, it is essential that the presurgical cognitive function of bypass patients is well-characterized.

Two methods have predominated in previous examinations of presurgical cognitive function, with candidates' cognitive performances being compared with those of a healthy control group or published cognitive test score means derived from a particular population and stratified by relevant demographic factors (normative data). Of the previous studies examining bypass candidates in detail, one used a healthy control group recruited from the community [8], another two studies used published normative data [6, 7], while none of them used both methods. Although Rosengart and colleagues [9] have used both normative data and a control group, the patient sample used in this study was not limited to bypass candidates. Because both methods have their strengths and weaknesses, using more than one method of comparison can be useful in accurately characterizing presurgical cognitive function in bypass candidates. Therefore, the present study was designed to evaluate bypass candidates' cognitive performances using both a healthy control group (control comparison) and published normative data (normative comparison).

In the present study, a large battery of cognitive tests was used to evaluate cognitive function. Candidates were compared with controls using cognitive test scores as well as incidence of cognitive impairment. Unlike previous studies, which utilized normative data solely as reference points to calculate the incidence of cognitive impairment [6, 7, 9], the present study utilized normative data in three different ways.

The primary aim of the present study was to extend the findings of previous studies by comparing bypass candidates' cognitive performances with both a healthy control group and published normative data using varied and different methods, particularly in the normative comparison.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 Acknowledgments
 References
 
Participants were patients consecutively listed for CABGS at The Royal Melbourne Hospital in Melbourne, Australia and recruited for a randomized trial comparing cognitive outcomes in off-pump surgery with conventional on-pump bypass surgery. Details of the trial are described elsewhere [13]. Eligible patients were those who were undergoing first-time elective CABGS, without concurrent valve or other cardiac surgical procedures, had no prior history of stroke or carotid occlusion greater than 95%, and were considered suitable for off-pump or on-pump techniques. Institutional ethics committee approval was obtained for this study in September 1999 and written consent was obtained from all patients.

Of 117 eligible bypass candidates, 109 were recruited between July 2001 and April 2004, while eight were excluded. Exclusion criteria for these patients were the presence of a neurologic or psychiatric condition with cognitive impairment, inadequate English, or participant refusal. A group of healthy individuals (n = 25) without a history of cardiovascular or coronary artery disease and ratio-matched on age, gender, and education to the bypass candidates, was recruited from the local community and used as a healthy control group. The cognitive performances of this group were used as reference points with which to compare candidate performances.

Measures
Cognitive function was assessed using 11 standardized cognitive tests, covering a variety of domains (Table 1). Test selection criteria included use in previous studies examining cognitive function in cardiac patients, published norms, adequacy of psychometric properties (ie, reliability and validity), brevity, and ease of administration [12, 14]. Psychometrically comparable short forms were used wherever possible. Standard recommendations were followed for test administration and scoring [15, 16].


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  		Table 1. Cognitive Tests Administered, With Corresponding Cognitive Function Assessed and Key Variables Selected for Analysis
 
Tests took approximately 60 minutes to administer. To minimize fatigue effects on cognitive performances, two predetermined orders of test administration were administered alternately to participants. Assessments were conducted by doctoral level neuropsychology interns supervised by a qualified neuropsychologist. The cognitive testing for patients was undertaken at a mean of 23.3 (SD = 28.6) days and a median of 13 days prior to bypass surgery. As indicated by the standard deviation, this time interval varied widely, with a range of one day to 140 days prior to surgery due to variations in the wait list period. Testing on the same day as surgery was avoided.

Sociodemographic characteristics including age, gender, and education were also recorded along with an estimate of intelligence quotient (IQ), which was obtained using the National Adult Reading Test – Revised [17]. Presurgical anxiety and depression in bypass candidates was measured using the Hospital Anxiety and Depression Scale.

Data Analysis
Of the 11 cognitive tests administered, the Stroop test was excluded from the analyses due to problems in the spectral resolution of the reproduced stimulus cards. As the tests generated a large number of variables, 12 key measures were selected for analysis (Table 1). Selection criteria consisted of (a) relative loadings of test variables on a principal components analysis, (b) use of test summary scores when they were found to correlate highly with subtest scores, (c) use in previous studies, and (d) expert opinion based on theoretical grounds.

Cognitive test scores for bypass candidates and the healthy control group were compared using t tests for independent groups. Multivariate analysis was undertaken to compare both groups on overall cognition, in addition to univariate tests for each individual dependent variable. For Grooved Pegboard and Trails A and B, a higher test score indicated poorer cognitive function. For all other tests, higher scores indicated better performances.

For the comparison of patient cognitive test performances with published test norms (normative comparison), norms for most tests were selected from standard neuropsychological handbooks [16, 18], except for Grooved Pegboard [19], Boston Naming [20], Digit Symbol, Digit Span [21], and Visual Reproduction [21, 22], which were obtained from the relevant sources referenced. The normative comparison was undertaken using two different methods. In the first method, since the demographic characteristics of the normative sample differed from the study sample, published normative means for each cognitive test were weighted in order to make the norms compatible for direct comparison. This was accomplished by using the percentage of bypass candidates that were in various demographic subgroups (ie, age, gender, and education) to weight the normative data to match the demographic distribution of our sample. The weighted norm was then used as the criterion in a one-sample t test. This same normative comparison was also undertaken for the control group with weighted norms calculated from the demographic distribution of the control group. In the second method, the test score distribution of bypass candidates was compared with that of a normal distribution. For each cognitive test, normative data were used to classify candidates' cognitive performances as being either "greater than or equal to 1 SD below the normative mean," "within 1 SD of the normative mean,"' or "greater than or equal to 1 SD above the normative mean." Using {chi}2 tests, percentages of candidates in each of the three categories were compared with expected percentages derived from the corresponding areas under the curve of a standard normal distribution (15.9%, 68.2%, and 15.9%, respectively).

Incidence of cognitive impairment was calculated for bypass candidates and was defined as test scores that were 1.0 SD or greater below published normative means [9, 16, 21, 23]. Percentages of those cognitive impaired versus not impaired in the bypass candidates and healthy controls were compared using {chi}2 tests.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 Acknowledgments
 References
 
Sociodemographic characteristics for bypass candidates and healthy controls are shown in Table 2 together with bypass candidates' presurgical medical history, and anxiety and depression scores. Bypass candidates did not differ from the healthy control group in any sociodemographic characteristic (Table 2). The cognitive function of the healthy control group was generally comparable with that of the population from which the normative information was derived, with test scores being neither uniformly better nor worse than test norms (data not shown).


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  		Table 2. Sociodemographic Characteristics of Bypass Candidates and Healthy Controls, With Presurgical Medical History and Emotional Status of Bypass Candidates
 
There was a significant difference between bypass candidates and the control group in terms of overall cognitive test scores F (12,103) = 2.998, p is less than 0 .01, with candidates' cognitive test scores being lower than those of the control group. When cognitive tests were examined individually, bypass candidates showed significantly reduced performances on the Rey Auditory Verbal Learning, Digit Symbol, and Digit Span tests (Table 3). Due to the unequal sample sizes, the homogeneity of variance assumption was examined with the intention of using a Welsh or Brown-Forsythe test to adjust for inequalities in variance. However, all dependent variables met homogeneity of variance requirements.


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  		Table 3. Means and Standard Deviations for Cognitive Tests for Bypass Candidates and Control Group Including Results of Comparisons Between Bypass Candidates and the Healthy Controls
 
For the normative comparison, bypass candidates' cognitive test scores were significantly different from weighted normative means on all but one test (Table 4). Of the tests that were significantly different, bypass candidates' test scores were consistently lower than the weighted norm for all tests except visual reproduction. Finally, the percentages of candidates classified as being 1 SD or greater below the normative mean, within 1 SD of the normative mean, or 1 SD or greater above the normative mean were significantly different from the percentages expected from a normal distribution. Higher percentages of candidates' cognitive performances than would be expected were classified as being 1 SD or greater below the normative mean for all tests except visual reproduction. This result again indicates reduced cognitive performances for bypass candidates (Table 5).


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  		Table 4. Comparisons Between Weighted Norms and Mean Scores for Cognitive Tests
 

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  		Table 5. Comparison of Percentages of Candidates for Bypass, With Expected Percentages Derived From a Normal Distribution
 
The incidences of cognitive impairment for bypass candidates and healthy controls are reported in Table 6. Bypass candidates showed significantly higher percentages of cognitive impairment on the Rey Auditory Verbal Learning Test and Digit Symbol with a similar trend on Digit Span.


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  		Table 6. Comparison of the Percentages of Cognitively Impaired Versus Not Impaired for Bypass Candidates and Healthy Controls
 

   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
Acknowledgments
 References
 
The current finding of a pattern of reduced cognitive performances in bypass candidates is consistent with a growing number of studies [6–9]. The present study extends previous studies by demonstrating reduced cognitive performances in bypass candidates compared with both a healthy control group and published norms using different methods of comparison.

It has been suggested that cognitive impairment prior to bypass might be explained in terms of patients' emotional distress [5]. In the present study, bypass candidates' anxiety and depression mean scores (Table 2) are greater than the clinical cutoff scores of 6 or greater for anxiety and 4 or greater for depression recommended for cardiac patients [24], although they are within the normal range (≤ 7) according to the test manual [25]. As we did not assess anxiety and depression in the healthy control group, we were unable to control for emotional factors in the analysis. However, recent studies suggest that emotional factors may not play a part in cognitive impairment prior to cardiac surgery. One such study showed poorer cognitive function in bypass candidates compared with controls even after controlling for anxiety and depression [8]. Other studies have similarly concluded that anxiety and depression have almost no effect on cognitive performances before cardiac surgery [9, 26]. That cardiac patients not awaiting surgery also exhibit similar cognitive impairment as bypass candidates [27], further suggests that cognitive difficulties observed prior to cardiac surgery cannot be attributed to presurgical emotional distress. Therefore, it appears that reduced cognitive performances in bypass candidates cannot be explained solely by presurgical emotional distress.

The cardiac disease process itself has been implicated as a causative factor in bypass candidates' reduced cognitive performances [3, 8, 27–29]. Candidates for other cardiac procedures, including angioplasty [9] and heart transplantation [30] have similarly been found to exhibit cognitive impairment. Previous studies have reported reduced cognitive performances in cardiac patients with a history of coronary artery disease who were recruited through cardiac rehabilitation programs [28, 31, 32]. According to Moser and colleagues [28], cognitive impairments were associated with both hypertension and reduced ejection fraction. This is consistent with recent reviews that have linked cognitive impairment to congestive heart failure, chronic hypertension, atherosclerosis, and cardiac arrhythmias as well as after acute myocardial infarction and cardiac arrest [33–35]. It has been suggested that unrecognized cerebrovascular disease can accompany cardiovascular disease, as the underlying pathophysiology of both disease processes is similar [28, 33, 35]. Because the brain requires a constant blood supply, disruptions to the functioning of the heart, such as reduction in cardiac output, can result in cerebrovascular consequences [33, 35]. Therefore, it is not surprising that bypass candidates, with many cardiac disease-related risk factors for cognitive impairment (Table 2), would exhibit reduced cognitive performances prior to bypass. Further investigation is required to understand potential predictors of prebypass cognitive function.

Patients in the present study were recruited for a randomized trial comparing off-pump surgery with conventional on-pump bypass surgery, with selection being based on whether they would be suitable for either technique. Therefore, it is possible that the present sample may be somewhat healthier and better functioning than an overall population of cardiac patients. The exclusion of those patients with diagnosed cognitive impairment further reinforces the expectation that our sample would be relatively cognitively intact. The present findings might therefore represent an underestimate of the level of cognitive difficulties evident among bypass candidates in general.

The strengths of this study include the use of both a healthy control group and normative data as reference points in evaluating bypass candidate cognitive performances and the use of multiple methods of comparison. In the control group comparison this study used continuous test scores as the primary variables of analysis, making them amenable to more powerful statistical techniques. The test score distribution of the entire bypass candidate group was examined in both the control comparison and the normative comparison, thereby providing a more comprehensive picture. However, the exclusive use of continuous test scores may mask the subset of patients who do exhibit clinically significant deficits [29]. Additionally, despite the inherent difficulties in defining cognitive impairment, reporting of incidence rates has its usefulness. Therefore, incidence rates for cognitive impairment based on normative data are included. The definition of cognitive impairment used by Rosengart and colleagues [9] was adopted in this study. However, it must be noted that this is a rather lenient classification of impairment, which may not be reflective of true clinically meaningful deficits as it also includes those who were "low average" or "borderline" [21, 23, 36]. At the same time, more stringent cutoffs, although more clinically relevant, may result in low numbers being classified as impaired, invalidating statistical comparisons. The range of incidences of impairment in our study (13.8% to 44.2%) is comparable with the rates of 4.7% to 51.2% [7] and 1% to 57% [9] reported in previous studies.

However, the study has some limitations. The healthy control group used in this study, while being well-matched to the patient group, was relatively small. A larger control group matched using stratified matching techniques would be better suited for comparison with the bypass candidates. While based on larger, stratified samples, the normative data were collected in the United States of America and Canada, with the exception of the Rey Auditory Verbal Learning Test, for which Australian-based normative data were used. As it has been suggested that normative data may not be ideal for comparisons across cultures [18], the use of local normative data would have been preferred. This highlights the need for the development of adequate local normative data or restandardization of existing normative data with culturally relevant adjustments.

In conclusion, candidates for CABGS exhibit reduced cognitive performances compared with a healthy control group of similar age, gender, and education ratios and age-adjusted normative data. However, relatively little is known about the impact of these reduced cognitive performances in everyday life. Further investigation is required to understand better the causal mechanisms of these findings and to delineate the effects of these difficulties in everyday life.


   Acknowledgments
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
References
 
Funding for this study was provided by the Percy Baxter Charitable Trust, the Eirene Lucas Foundation, and the Marian and EH Flack Trust. The authors wish to acknowledge the expertise of clinical neuropsychologist, Dr David Andrewes, The University of Melbourne, and Sue Rice and Penelope Davis, the Cardiothoracic Surgical Unit, The Royal Melbourne Hospital for assistance in collecting medical data.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 

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