Neurocognitive Deficit Following Coronary Artery Bypass Grafting: A Prospective Study of Surgical Patients and Nonsurgical Controls

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1 Neurocognitive Deficit Following Coronary Artery Bypass Grafting: A Prospective Study of Surgical Patients and Nonsurgical Controls Daniel Zimpfer, MD, Martin Czerny, MD, Ferdinand Vogt, MD, Philipp Schuch, MS, Ludwig Kramer, MD, Ernst Wolner, MD, PhD, and Michael Grimm, MD Departments of Cardiothoracic Surgery and Internal Medicine, University of Vienna, Vienna, Department of Cardiac Surgery, University of Innsbruck, Innsbruck, Austria Background. To objectively measure long-term neurocognitive deficit in patients undergoing coronary artery bypass grafting and compare the findings with nonsurgical controls. Methods. We prospectively measured neurocognitive function in patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (n 104; mean age 64.1 years old; EuroSCORE 2.7 [means]). A cohort of age- and sex-matched patients (n 80; mean age 63.4 years old) served as nonsurgical controls. After CABG, neurocognitive function was serially reevaluated at 7-day (n 104), 4-month (n 100), and 3-year follow-up (n 88). Neurocognitive function was objectively measured by means of cognitive P300 evoked potentials. Additionally, standard psychometric tests were performed (Trailmaking Test A, Mini Mental State Examination). Results. As compared to preoperative measures ( ms), cognitive P300 evoked potentials were prolonged ( impaired) at 7-day ( ms; p 0.001), 4-month ( ms; p 0.08), and 3-year follow-up ( ms; p 0.002), respectively. Trailmaking Test A was abnormal, as compared to preoperative, at 3-year follow-up (p < 0.001). Before the operation, surgical patients were fully comparable in P300 measures to nonsurgical controls ( ms; p 0.362). Most importantly, throughout the entire postoperative follow-up cognitive measures in surgical patients were prolonged ( impaired) as compared with controls (7-day p 0.001; 4-month p and 3-year p 0.003, respectively). In stepwise multivariate regression analysis, neurocognitive deficit at 4-month follow-up (p < 0.001), age (p 0.012), and persistent atrial fibrillation (p 0.024) were predictive for long-term neurocognitive deficit at 3-year follow-up. Conclusions. As shown by means of objective measures, and in comparison to nonsurgical controls, coronary artery bypass grafting with cardiopulmonary bypass grafting causes long-term neurocognitive deficit. (Ann Thorac Surg 2004;78:513 9) 2004 by The Society of Thoracic Surgeons Due to the continuous improvement of surgical techniques, extracorporal circulation as well as an aesthesia and intensive care, mortality and morbidity following coronary artery bypass grafting (CABG) have been significantly reduced. Therefore, adverse effects of coronary artery bypass with cardiopulmonary bypass such as neurocognitive deficit are increasingly being recognized. Neurocognitive deficit has been reported to affect up to 80% of patients at hospital discharge and up to 42% of patients 5 years after surgery [1 4]. Neurocognitive deficit has been associated with an up to 10% increase in perioperative mortality and increase in length of in hospital stay, a prolonged process of rehabilitation and a later return to normal life [3]. This is associated with a tremendous increased use of health care resources. The aim of the present study was to objectively measure long-term neurocognitive deficit following isolated Accepted for publication Dec 29, Address reprint requests to Dr Grimm, Department of Cardiothoracic Surgery, University of Vienna, Wahringer Guertel 18-20, A-1090 Vienna, Austria; michael.grimm@akh-wien.ac.at. coronary artery bypass grafting, to compare the findings with nonsurgical controls and to elucidate factors associated with long-term neurocognitive deficit. Defining patients with increased risk for long-term neurocognitive deficit will enable us to identify these patients in the future and develop treatment strategies especially devoted to them. Material and Methods Patients After approval was obtained by the Ethics Committee of the University of Vienna, 105 patients who underwent elective coronary artery bypass grafting at our department between January and December 1999, gave their written informed consent and were enrolled in this prospective study. Exclusion criteria were a history of one of the following medical conditions [1]: prior stroke with residual deficit [2], uncontrolled hypertension [4], carotid artery stenosis 75% [4], psychiatric illness requiring treatment [5], alcoholism [6], renal disease (defined as a 2004 by The Society of Thoracic Surgeons /04/$30.00 Published by Elsevier Inc doi: /j.athoracsur

2 514 ZIMPFER ET AL Ann Thorac Surg NEUROCOGNITIVE DEFICIT FOLLOWING CABG 2004;78:513 9 creatinine more than 2.0 mg/dl [177 mol per liter]) and [7] active liver disease. Nonsurgical Controls For nonsurgical controls, we screened patients admitted to the Department of Internal Medicine. The same exclusion criteria used in patients undergoing CABG were applied on control patients. Patients were contacted by the study coordinator. Patients were informed by the study coordinator about the planned tests as well as the frequency of reexamination. All patients serving as controls had to give their written and informed consent. Tests were not performed as part of another study. Of the patients contacted, 80 gave their written and informed consent and were enrolled. Preoperative Risk Stratification Preoperative risk stratification was performed using the European System for Cardiac Operative Risk Evaluation (EuroSCORE). The EuroSCORE is a risk stratification system to help in the assessment of quality of cardiac surgical care. The score consists of patient-, cardiac- and operation-related factors [5]. Neurocognitive Testing Neurocognitive testing and physical examinations were completed preoperatively, 7 days, 4 months, and 3 years after surgery, respectively. All examinations were performed individually by the same experienced investigator. Neurocognitive testing consisted of cognitive P300 evoked potentials, Mini Mental State Examination, and Trailmaking Test A. To avoid any influences due to biorhythm, all investigations were performed in the afternoon under comparable conditions. Special care was taken to ensure that patients were free from narcotics and sedatives for at least two days before testing. Cognitive P300 Evoked Potentials Cognitive P300 evoked potentials have previously been used to measure neurocognitive function in various metabolic disorders, patients undergoing heart transplantation and patients undergoing open heart surgery [6 10]. Cognitive P300 evoked potential are the result of an activation of a widespread network of cortical structures, including association areas in the parietal, temporal and prefrontal cortex, as well as the hippocampus [11]. As a result of the involvement of these brain regions in the P300 generation, P300 can be used as a general indicator for neurocognitive function [12 14]. Cognitive P300 evoked potentials were recorded with Ag/AgCl electrodes on a Nicolet 2000 (Nicolet, Madison, WI). P300 evoked potentials were generated following a binaurally presented tone discrimination paradigm (odd-ball paradigm) with frequent (80%) tones of 1000 Hz and rare (20%) target-tones of 2000 Hz at 75 db HL. Filter bandpass was 0.01 to 30 Hz. Active electrodes were placed at Cz (vertex) and Fz (frontal), respectively, and referenced to linked earlobe A1/2 electrodes (10/20 international system) [15]. During the paradigm, the patients were instructed to keep a running mental count of the rare 2000 Hz target tones. To verify attention, P300 recordings with a discrepancy of more than 10% between the actual number of stimuli and the number counted by the patients were rejected and repeated. P300 evoked potential recording resulted in a stable sequence of positive and negative peaks. Latencies (milliseconds) of the cognitive P300 peak were assessed. To confirm reproducibility, two sets of P300 measurements were recorded in all patients. P300 evoked potential findings were compared with those of 80 age- and sex-matched control patients (mean age years, age range years old). Psychometric Tests Immediately after P300 recording, Trailmaking Test A (TTA) and Mini Mental State Examination (MMSE) were performed [16, 17]. Mini Mental state examination was used to ensure that all patients entering the present study were free from overt neurologic impairment or dementia. To minimize learning effects, five different Trailmaking Tables were randomly used. Follow-Up In addition to neurocognitive testing, patients were studied by means of echocardiography, electrocardiogram (ECG), blood tests, and clinical investigations at all points of follow-up. Persistent atrial fibrillation was defined as presence of atrial fibrillation at 7-day, 4-month, and 3-year follow-up. Anesthesia and Surgical Procedure General anesthesia was administered using midazolam, ethmidate, fentanyl and pancuronium. Surgical access was gained through a median sternotomy in all patients. A transesophageal echocardiography probe (TEE) was placed in all patients. In the study group standard cardiopulmonary bypass (CPB) technique with membrane oxygenators (Bard HF 5701; C.R. Bard Inc, Havorhill, MA), roller pumps, mild hypothermia (35 C) was used. Mean arterial pressure during and after CPB was kept above 50 mm Hg. Intensive care treatment was performed according to institutional standards. Statistical Analysis Data are reported as mean SD. Comparison of P300 evoked potentials and standard psychometric test were performed using analysis of variance (ANOVA) after testing for normality of distribution. Age and base line test scores served as covariates and group classification (CABG vs controls) as the independent variable. The time course of neurocognitive function was analyzed by means of paired t-test. As multiple testing was performed a Bonferroni-Holm correction was performed. Categorical variables were compared using 2 test or Fischer s exact test as appropriate. To test the simultaneous influence of variables on changes of P300 peak latencies, stepwise multivariable regression analysis was performed. Neurocognitive deficit was defined as a decline of more than 1 standard deviation as compared to preoperative measures. In order to test if there is a correlation between individual changes in cognitive P300 audi-

3 Ann Thorac Surg ZIMPFER ET AL 2004;78:513 9 NEUROCOGNITIVE DEFICIT FOLLOWING CABG 515 Table 1. Patient Characteristics Variable CABG Controls p Value Number Age (mean SD) Age range (yrs.) Sex (m, %) Ethnicity (white, %) Married (%) Mean education level (years) Smoking (%) Diabetes (%) Hypertension (%) Previous cerebrovascular accident (%) Ejection fraction (%, mean SD) 58 1 Diseased vessels (vessels, mean SD) EuroSCORE (points, mean SD) CABG coronary artery bypass grafting. tory evoked potentials and Trail Making Test A, a regression analysis was performed. The entrance level into multivariable regression analysis was set to p value less than or equal to 0.15 based on univariate analysis; p values less than 0.05 were considered as significant, two sided. The study was analyzed using SAS, version 8 (Cary, NC). Results One hundred four patients undergoing isolated coronary artery bypass grafting at our institution were prospectively followed. The baseline characteristics of patients as well as controls are given in Table 1. Clinical Outcome Because only operative survivors entered this prospective study, we observed no perioperative deaths. Operative data and clinical outcome are given in Table 2. Table 2. Clinical Outcome Operative data Operation time (min, mean SD) CPB time (min, mean SD) Cross-clamp time (min, mean SD) Number of grafts (n, mean SD) In-ICU stay (days, mean SD) 2 2 In-hospital stay (days, mean SD) 12 8 Clinical outcome Death during follow-up (%) 1.9 Myocardial infarction (postoperative, %) 2.8 Stroke (postoperative, %) 2.0 Atrial fibrillation 7-day follow-up (%) 28.8 Atrial fibrillation 4-month follow-up (%) 23.8 Atrial fibrillation 3-year follow-up (%) 23.8 CPB cardiopulmonary bypass; ICU intensive care unit; SD standard deviation. Cognitive P300 Evoked Potentials Cognitive P300 evoked potentials of patients undergoing coronary artery bypass grafting, and age- and sexmatched patients were comparable before operation (CABG ms; controls ms; p ; Fig 1A). In both groups, controls and patients undergoing coronary artery bypass grafting, P300 peak latencies were strictly age dependent before the operation. After coronary artery bypass grafting P300 evoked potentials were prolonged ( impaired) at 7-day ( ms, p 0.001), 4-month ( ms, p 0.008), and 3-year follow-up ( ms, p 0.002) as compared to preoperative values ( ms; Fig 2). When compared with control patients, neurocognitive function was impaired at 7-day (controls ms, p 0.001), 4-month (controls ms, p 0.002), and 3-year follow-up (controls ms, p 0.003; Figs 1B and 2). Furthermore, neurocognitive deficit was defined as a dichotomous variable enabling us to identify patients with neurocognitive deficit at 7-day, 4-month, and 3-year follow-up. Thereby, we found neurocognitive deficit in 51.3% at 7-day, in 48.8% at 4-month, and in 50.0% at 3-year follow-up. To elucidate which demographic and perioperative factors were associated with neurocognitive deficit at 3-year follow-up, suspected univariate predictors of cognitive decline were assessed by means of linear regression analysis (Table 3). Significant univariate predictors were neurocognitive deficit at 4-month follow-up (p 0.001), age (p 0.002) and persistent atrial fibrillation (p 0.003). The entrance level into multivariable regression analysis was set to p values less than or equal to 0.15 based on univariate analysis. Multivariate analysis revealed neurocognitive deficit at 4-month follow-up (p 0.001), age (p 0.012) and persistent atrial fibrillation (p 0.024) as independent predictors of neurocognitive deficit at 3-year follow-up. The inclusion of data for the patients lost for follow-up, patients with perioperative stroke or patients who died during the period of follow-up did not appreciable change the predictors or their significance. Standard Psychometric Tests To detect clinically overt changes of neurocognitive function we used Mini Mental State examination and Trailmaking Test A. Mini Mental State examination showed no statistically significant changes, indicating that all patients entering the study were free from overt neurologic disorders or dementia throughout the study period. Results of Mini Mental State examination are given in Table 4. Trailmaking Test A in part supports the findings of cognitive P300 potentials, however it was not discriminative. Results of Trailmaking Test A are given in Table 4. Correlation Between Cognitive P300 Potentials and Trailmaking Test A In order to firmly establish a strong correlation between individual changes in cognitive P300 auditory evoked

4 516 ZIMPFER ET AL Ann Thorac Surg NEUROCOGNITIVE DEFICIT FOLLOWING CABG 2004;78:513 9 Fig 1. (A) P300 peak latencies of patients undergoing coronary artery bypass grafting (n 104) before operation; individual measurements are indicated by. Solid line represents latency-age regression of age- and sex-matched controls; dotted lines represent upper and lower 95% confidence limits. (B) P300 peak latencies of patients undergoing coronary artery bypass grafting (n 88) at 3-year follow-up. Individual measurements are indicated by. Solid line represents latency age regression of age- and sex-matched controls (after a 3-year follow-up); dotted lines represent upper and lower 95% confidence limits. potentials and Trail Making Test A from preoperative to 3-years postoperative, a linear regression analysis was performed (R 0.672, R-square 0.452, p 0.006). Comment When compared with nonsurgical controls, coronary artery bypass grafting truly causes long-term neurocognitive deficit. Predictive variables for long-term neurocognitive deficit are neurocognitive deficit at 4-month follow-up, age, and persistent atrial fibrillation. Neurocognitive deficit, defined as a combination of deficits in memory, learning, concentration and visual motor response, is an adverse event of coronary artery bypass grafting with an incidence of up to 80% perhaps the most common adverse event [1 4, 8, 18]. Roach and colleagues [3] reported on a multi-institutional prospective study that that neurocognitive deficit is associated with increased mortality (10%), a twofold increase in hospital length of stay and a sixfold likelihood of discharge to a nursing home. This is associated with a tremendously increased use of health care resources. From the patients view, the impact of neurocognitive deficit is devastating as it has been shown to reduce subjective working capacity, decrease quality of life, job related abilities, productive working status and to impair car driving abilities [19, 20]. Summarizing, neurocognitive deficit is a drawback of coronary artery bypass grafting as it may reduce the merits of surgical intervention. On the basis of P300 measurements, we were able to show that neurocognitive function is impaired in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass at 7-day, 4-month, and 3-year (longterm) follow-up, as compared with preoperative and ageand sex-matched controls. Our data support previous findings indicating that postoperative neurocognitive decline may persist up to 5 years after surgery [1, 2, 4]. To assess long-term neurocognitive function following CABG we used a previously described diagnostic tool consisting of cognitive P300 evoked potentials and standard psychometric tests [7, 8, 9]. Previous series used standard psychometric test batteries to assess long-term neurocognitive function [1, 2, 4, 18, 19, 21]. Although such batteries are well introduced, it is generally accepted that psychometric test batteries are not without biases, eg, in part because of long performance times (stressing attention), visual impairment, influence of psychomotor function, level of education and learning effects [22 28]. The latter are of particular interest for follow-up studies, especially in CABG patients representing eldery, in part multimorbid patients. P300 peak latencies increase with age in healthy patients. The clinical relevance of cognitive P300 evoked potentials is based on the fact that they were demonstrated to be related to cognitive impairment rating, rapid evaluation of cognitive function tests, orientation, stimulus evaluation, selective attention, visual pattern recognition, and digit span, and were revealed to be much more sensitive in detecting neurocognitive deficit than psychometric tests or electroencephalograms [6, 7, 13]. Moreover, P300 technique has a very low intraindiviual test-retest variability with a coefficient of variation of below 2%, which further stresses its usefulness for cognitive follow-up studies [7]. All P300 recordings were taken repeatedly (double tracing) to confirm reproducibility of measurements. The high standard deviations of mean P300 peak latencies in patients and ageand sex-matched control patients are the result of age dependency of cognitive P300 measurements. Psychometric tests in part confirm the findings of P300 measurements: Mini Mental State examination, a standard test of cognitive impairment, was normal in all patients (ranging from 27 to the maximum of 30). This indicates that only patients without overt neurologic impairment or dementia entered the study. More discriminating were the findings in Trailmaking Test A. Patients undergoing coronary artery bypass grafting scored significantly ab-

5 Ann Thorac Surg ZIMPFER ET AL 2004;78:513 9 NEUROCOGNITIVE DEFICIT FOLLOWING CABG 517 Fig 2. Graph illustrates serial assessments of cognitive brain function by cognitive P300 evoked potentials. The black line represents patients undergoing coronary artery bypass grafting, the gray line represents age- and sex-matched controls. *p 0.05 compared with preoperative values; p 0.05 within the two groups. (FUP follow-up; pre-op pre-operative.) normal at 3-year follow-up. Furthermore we found a good correlation between individual development of cognitive P300 peak latencies and Trailmaking Test A. Our results suggest that coronary artery bypass grafting with cardiopulmonary bypass may cause irreversible damage to cerebral tissue resulting in significantly impaired neurocognitive function. Suspected underlying mechanisms are impaired cerebral perfusion during CPB, postoperative systemic inflammatory response, and micro- and macroembolism [29]. The finding that neurocognitive deficit at 4-month follow-up and advanced age are independent predictors for long-term neurocognitive deficit suggests that the amount and nature of damage varies in different patients and that elderly patients are at higher risk to develop irreversible damage. Possible underlying mechanisms rendering elderly patients especially vulnerable might be advanced sclerosis of the ascending aorta (a possible source of micro and macroemboli during cross clamping and cannualtion) as well as partial loss of cerebral autoregulation resulting from occult cerebrovascular disease [30]. There might also be decreased ability to recover and to compensate in these patients. The pathophysiology of the impact of atrial fibrillation, although previously described, has not yet been clarified [31]. Suspected underlying mechanisms are an increased potential for thrombus formation and subsequent embolization into cerebral tissue and atrial fibrillation-related decrease in cardiac output [32]. Nevertheless, further investigations are warranted to clarify the underlying mechanisms. Specifically, it remains to be studied, whether in the future this atrial fibrillationrelated neurocognitive impairment may be improved by additional surgical MAZE procedure. Limitations Our study is limited by a certain loss of follow-up that is inevitable in a study that follows patients for 3 years. However, the loss of follow-up is comparable to other studies dealing with the same topic [1, 2, 4]. Another limitation of the present study is that we provide normative data obtained in age- and sex-matched controls only for cognitive P300 evoked potentials. The present data are only valid for elective patients with a comparable age range undergoing coronary artery bypass grafting with mildly hypothermic cardiopulmonary bypass and cannot be extrapolated to patients undergoing other than elective isolated coronary artery bypass grafting. Patients undergoing coronary artery bypass grafting were matched with their nonsurgical control counterparts with regard to age and sex. No further matching with regard to risk factors for cardiovascular disease has been performed. Nevertheless, we found non difference between risk factors for cardiovascular disease except incidence of hypertension between patients undergoing coronary artery bypass grafting and nonsurgical controls. By means of objective measures the present study proofs the evidence of long-term neurocognitive deficit following coronary bypass surgery and strongly supports its clinical significance by comparison to, nonsurgical controls. Predictors for long-term neurocognitive deficit are neurocognitive deficit at 4-month follow-up, age and persistent atrial fibrillation. These data will enable us to Table 3. Stepwise Linear Regression Analysis: Predictors for 3-Year Neurocognitive Deficit Variable Univariable Regression p Value Multivariable Regression p Value 4-Month deficit Age Persistent atrial fibrillation CPB time Operation time Diabetes Hypertension Ejection fraction Diseased vessels Cross-clamp time Number of grafts CPB cardiopulmonary bypass. Table 4. Results of Standard Psychometric Tests in Patients Undergoing Coronary Artery Bypass Grafting Test a Value p Value MMSE Preoperative Day follow-up Month follow-up Year follow-up TTA Preoperative Day follow-up Month follow-up Year follow-up a Higher scores indicate better cognitive brain function, with the exception of scores on the TTA for which lower scores indicate better cognitive function. MMSE mini mental state examination; TTA trailmaking test A.

6 518 ZIMPFER ET AL Ann Thorac Surg NEUROCOGNITIVE DEFICIT FOLLOWING CABG 2004;78:513 9 identify patients with increased risk for long-term neurocognitive deficit in the future and to develop treatment strategies especially devoted to them. We thank Daniela Dunkler, MS(Stat), for the statistical analysis of the work. References 1. Newman MF, Kirchner JL, Phillips-Bute B, et al. Longitudinal assessment of neurocognitive function after coronaryartery bypass surgery. N Engl J Med 2001;344: Sotaniemi KA, Mononen H, Hokkanen TE. Long-term cerebral outcome after open-heart surgery: a five-year neuropsychological follow-up study. Stroke 1986;17: Roach GW, Kanchuger M, Mangano, et al. Adverse cerebral outcome after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. N Engl J Med 1996;335: Murkin JM, Baird DL, Martzke JS, et al. Long-term neurological, and neuropsychological outcome 3 years after coronary artery bypass surgery (abstr). Anesth Analg 1996;82: Nashef SA, Roques F, Michel P, et al. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg 1999;16: De Feo P, Gallai V, Mazzotta G, et al. Modest decrements in plasma glucose concentration cause early impairment in cognitive function and later activation of glucose counterregulation in the absence of hypoglycemic symptoms in normal man. J Clin Invest 1988;82: Grimm M, Yeganehfar W, Laufer G, et al. Cyclosporine may affect improvement of cognitive brain function after successful cardiac transplantation. Circulation 1996;94: Zimpfer D, Czerny M, Kilo J, et al. Cognitive deficit after aortic valve replacement. Ann Thorac Surg 2002;74: Engelhardt W, Dierks T, Pause M, et al. P300-mapping a neurophysiological tool to quantify cerebral dysfunction after coronary artery bypass grafting. Eur J Cardiothorac Surg 1995;9: Kiehl KA, Laurens KR, Duty TL, et al. Neuronal sources involved in auditory target detection and novelty processing: an event related fmri study. Psychophysiology 2001;38: Picton TW. The P300 wave of the human event-related potential. J Clin Neurophysiol 1992;9: Polich J, Ehlers CL, Otis S. P300 latency reflects the degree of cognitive decline in dementing illness. Electroencephalogr Clin Neurophysiol 1986;63: Pozessere G, Valle E, de Crignis S. Abnormalities of cognitive functions in IDDM revealed by P300 event-related potential analysis. Comparison with short-latency evoked potentials and psychometric tests. Diabetes 1991;40: Polich J. P300 clinical utility and control of variability. J Clin Neurophysiol 1998;15: Jasper HH. The ten/twenty electrode system of the International Federation. Electroencephalogr Clin Neurophysiol 1958;10: Reitan RM. Validity of the Trail Making Test as an indication of organic brain damage. Percept Mot Skills 1958;8: Folstein MF, Folstein SE, McHugh PR. Mini Mental State. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12: Blumenthal JA, Mahanna EP, Madden DJ. Methodological issues in the assessment of neuropsychologic function after cardiac surgery. Ann Thorac Surg 1995;59: Newman MF, Grocott HP, Mathew JP, et al. Report of the substudy assessing the impact of neurocognitive function on quality of life 5 years after cardiac surgery. Stroke 2001;32: Ahlgren E, Lundqvist A, Nordlund A. Neurocognitive impairment and driving performance after coronary artery bypass surgery. Eur J Cardiothorac Surg 2003;23: Selnes OA, Grega MA, Borowicz LM Jr, et al. Cognitive changes with coronary artery disease: a prospective study of coronary artery bypass graft patients and nonsurgical controls. Ann Thorac Surg 2003;75: Kempen JH, Krichevsky M, Feldman ST. Effect of visual impairment on neuropsychological test performance. J Clin Exp Neuropsychol 1994;16: Teresi JA, Golden RR, Cross P, et al. Item bias in cognitive screening measures: comparisons of elderly white, Afro- American, Hispanic and high and low education subgroups. J Clin Epidemiol 1995;48: Rossini Ed, Karl MA. The Trail Making Test A and B: a technical note on structural nonequivalence. Percept Mot Skills 1994;78: Gil R, Neau JP, Toullat G. Parkinson disease and cognitive evoked potentials. Rev Neurol (Paris) 1989;145: Courchesne E, Hillyard SA, Galambos R. Stimulus novelty, task relevance and the visual evoked potential in man. Electroencephalogr Clin Neurophysiol 1975;39: McCarthy G, Donchin E. A metric for thought: a comparison of P300 latency and reaction time. Science 1981;211: Ritter W, Simson R, Vaughan HG Jr, et al. Manipulation of event-related potential manifestations of information processing stages. Science 1982;218: Taylor KM. Brain damage during cardiopulmonary bypass. Ann Thorac Surg 1998;65: Stump DA, Tegeler CH, Newman SP. Older patients have more emboli during coronary bypass graft surgery. Anesthesiology 1992;103: Stanley TO, Mackensen GB, Grocott HP, et al. The impact of postoperative atrial fibrillation on neurocognitive outcome after coronary artery bypass graft surgery. Anesth Analg 2002;94: Creswell LL, Schuessler RB, Rosenbloom M, et al. Hazards of postoperative atrial arrhythmias. Ann Thorac Surg 1993; 56: INVITED COMMENTARY Numerous studies have made attempts in the past to quantify cognitive changes associated with the use of cardiopulmonary bypass, but it is only more recently that control groups for such studies have been introduced. In this issue, Zimpfer and associates compare neurophysiologic and cognitive changes in a group of patients undergoing coronary artery bypass grafting (CABG) surgery with those of a control group of inpatients on the internal medicine service. They conclude, largely on the basis of the P300 evoked potential changes, that the CABG patients have persistent neurocognitive impairment when retested at 7 days, 4 months, and 3 years after surgery. Results from recent studies relying on conventional neuropsychological tests have indicated that early postoperative cognitive changes after CABG may be transient and reversible, and that the majority of patients recover by approximately 3 months after surgery. The P300 results in the present study did not show this trend, however, although the authors have previously reported 2004 by The Society of Thoracic Surgeons /04/$30.00 Published by Elsevier Inc doi: /j.athoracsur