Chapter II. Review of Literature

Transcription

1 53 Chapter II Review of Literature This chapter provides a review of the major studies in the area of myocardial infarction with a focus on the variables included in the present study. An important clinical as well as research use of neuropsychological testing is to evaluate changes in cognitive performance over time. In the context of myocardial infarction and following cardiac surgery, preoperative baseline testing followed by one or more postoperative assessments has become an established method for evaluating the possible impact of myocardial infarction and bypass surgery on cognitive outcomes and depression. However, it is well known that the reported incidence of cognitive decline and depression after heart attack and coronary artery bypass grafting (CABG) surgery has varied quite significantly from one study to another. It has been widely assumed that this variability has resulted from differences in patient populations, follow-up time intervals, and the choice of clinical and neuropsychological measures. Studies related to neuropsychological deficits in myocardial infarction Engelhardt et al. (1995) explored cerebral dysfunction before and after cardiac surgery in 52 subjects (12 women, 40 men). The Syndrome short test for detection of concentration and memory disturbances was carried out. In addition, a letter cancellation test was performed. The Syndrome short test consisted verbal skill, immediate recall, capability to read, sort, rearrange,

2 54 differentiating, interference, intermediate-term recall, and recognition. All the test performances were compared pre-operatively and one week post-operatively. No differences between preoperative and postoperative test performances were found for letter cancellation, but an increase in the Syndrome short test score revealed a significant deterioration of cerebral function one week after CABG. Toner, Taylor, Newman, and Smith (1998) assessed cerebral functional deficits before and after cardiac surgery. Neuropsychological and quantitative electroencephalographic (EEG) changes were assessed in 62 coronary artery bypass graft surgery patients before surgery, within one week and two months after surgery. Neuropsychological tests like Rey auditory verbal learning test (immediate, recent, and delayed verbal memory), two computerized non-verbal memory tests (NVM level 1, 2), and Trail making tests A and B, Letter cancellation test, (attention and concent ration), Purdue pegboard test, Choice reaction time, Symbol digit replacement test and Block design test (perceptua l speed, psychomotor speed, and manual dexterity) were administered. It was found that at one week after surgery, 30 patients (48%), and at 2 months, 21 patients (34%) had significant cognitive deficits defined as failure on at least two of ten neuropsychological tests. One week after surgery, most deficits were found in test performances of attention and psychomotor speed, while performance on the tests of nonverbal memory improved. Two months after surgery, no significant deficit was found. Millar, Asburg, and Murray (2001) examined the effect of pre-existing cognitive impairment upon cognitive outcomes in 81 patients undergoing

3 55 coronary artery bypass graft surgery. Patients performed the Stroop neuropsychological screening test and other psychometric assessments prior to the surgery, and at six days and six months after surgery. They found that those with pre-existing cognitive deficits were significantly more vulnerable to post operative deficits. Reents, Muellges, Franke, Babin-Ebell, and Elert (2002) found cognitive dysfunction in patients with MI undergoing cardiac surgery. Forty-seven patients undergoing coronary artery bypass grafting (CABG) underwent preoperative and postoperative neuropsychological evaluation. Specific tests used and the investigated cognitive domains were Letter cancellation test (sustained attention and concentration), Trail making test B (attention, psychomotor speed, hand-eye coordination), Benton s visual retention test (visual short term memory, visuomotor abilities), Block design test from the Wechsler adult intelligence scale (clumsiness, visuospatial and cons tructive abilities), and Digit span test (verbal immediate memory, attention span). It was found that for all the patients, test scores of all tests showed a slight, but non-significant decrease on the sixth postoperative day as compared with baseline. According to individual test score differences, 16 patients had a test score decrease of one standard deviation or more in two or more of the five tests. Thus, in this study 16 of 47 patients (34%) showed early postoperative cognitive dysfunction. The neurological and neuropsychological deficits before and after CABG were examined by Bendszus, Koltzenburg, Warmuth-Metz, Hoffman, and Solymosi (2002). Thirty-five consecutive patients undergoing CABG with

4 56 cardiopulmonary bypass without major psychiatric or neurological disease were included in the study. The neurological test battery included Letter cancellation test (sustained attention and concentration), Benton visual retention test (visual short term memory and visuomotor abilities), Reitan trail making test A (attention, psychomotor speed and hand- eye coordination), and Block design test from the Wechsler adult intelligence scale (clumsiness, visuospatial and constructive abilities). The tests were administered by a neurologist 2 days before surgery, and on days three, six, and nine after surgery. There was significant difference between the pre-operative and post- operative groups in the test performances of Letter cancellation test, Benton visual retention test, and Reitan trail making test. Ahlgren, Lundqvist, Nordlund, Alen, and Rutberg (2003) evaluated cognitive functions and driving performance, both in real traffic and in advanced driving simulator before, and 4-6 weeks after CABG, in 27 patients. Neuropsychological test battery consisted of tests covering cognitive domains that have shown to be affected after cardiac surgery such as verbal and visual memory, psychomotor speed, attention and concentration. In addition a set of computerized tests considered important when assessing the ability to drive was included. The on road driving was done in actual traffic. Speed, maneuvering, lateral position, traffic behavior, and attention were evaluated. It was found that 48%of the patients showed a cognitive decline after CABG. Deterioration in test scores was most frequently seen in Trail making test A and B, Rey auditory verbal learning and memory (recognition), K-test, Simple reaction time and

5 57 Reaction time on two choice visual stimuli. It was also revealed that patients with a cognitive decline after CABG deteriorated in on-road driving to a greater extent than did patients without a cognitive decline. Browne, Halligan, Wade, and Taggart (2003) examined neuropsychological deficits and hypoxia before and after cardiac surgery in a sample of 75 patients undergoing CABG. Serial neuropsychological assessments were performed before surgical intervention, before discharge, and three months postoperatively using a battery of 10 psychometric tests. Tests included were Test A from the Adult memory information (inform ation processing speed), Trail making test B (set -shift thinking test), Auditory verbal learning test (memory), and the verbal fluency t est (executive function). They found that the mean cognitive index score decreased significantly at the fifth day of assessment after surgery but improved significantly beyond the baseline at the three month assessment. They also observed that a decreased cognitive index score at day five was a strong predictor of cognitive impairment at three months. Yosef et al. (2004) studied neurocognitive dysfunction before and after coronary artery bypass graft surgery. Neuropsychological tests were performed in 162 patients both preoperatively and at six weeks after surgery. Tests used were Short story module of Randt memory test, Digit span and Digit symbol subtests of Wechsler adult intelligence scale, and Trail making test B. the obtained results showed that 61 out of 162 patients (38%) demonstrated a significant decline in atleast one cognitive domain such as verbal memory, figure

6 58 memory, attention and concentration, abstraction and psychomotor processing speed. Carrasscal et al. (2005) evaluated prospectively the incidence of cognitive impairment in 132 coronary artery disease patients undergoing cardiac surgery using a single test called Paced Auditory Serial Addition Test (PASAT). PASAT involved tests of attention, concentration, information processing speed, and working memory. Evaluation was designed in 3 steps preoperative, immediate postoperative, and outpatient follow-up. It was evidenced that in 60 patients (45.5%), postope rative PASAT score decreased in more than 1 SD which is considered as significant neuropsychological impairment. Out of this, in 33 cases (55% of patients), the deficit persisted at follow-up. It was also found that patients with low preoperative PASAT score showed significant postoperative cognitive impairment. Knipp et al. (2005) aimed prospectively to evaluate brain injury before and after CABG using MRI and neuropsychological tests. Thirty patients undergoing CABG were investigated before surgery, and five days, and 4months after surgery. Tests used were Reitan trail making test B and Zimmermann s divided attention to assess attention and psychomotor speed, the verbal learning test to assess learning and memory of words, Digit span test of Wechsler memory scale to assess short term memory and working memory, the Corsi block- tapping test to assess short term and working memory for visual structures, and visuo-spatial function and recognition of categories and regularities of geometrical objects were tested with Horn s performance test. It

7 59 was revealed that early postoperatively, a significant deterioration of neurocognitive function was observed in 5 of the 13 tests as compared to baseline performance and the impairment was observed in almost all cognitive domains tested, particularly attention, rate of information processing and memory functions. The performance in visual constructive abilities and logical thinking were not affected early after surgery. A tendency towards declined function was seen in the domain of divided attention. Slater et al. (2009) investigated cognitive decline before and after coronary artery bypass grafting (CABG) in patients undergoing primary coronary artery bypass grafting using cardiopulmonary bypass. Neurocognitive testing was performed preoperatively, prior to discharge and at three months, using a battery of standardized neuropsychological tests to evaluate the domains of attention, memory, and manual dexterity. The results showed that of the 240 patients, 58 (29%) patients had cognitive decline at 3 months. All the above studies examined the neuropsychological outcome associated with cardiac surgery. Though the neuropsychological evaluation was done at pre-surgery and post-surgery, the cognitive deficits have been noticed only after surgery. However, these studies have ignored the presence of preoperative cognitive deficits, if any. Instead, they found significance of postoperative cognitive decline from preoperative cognitive performances. Postoperative neuropsychological impairment was noted in 34% to 48% of patients by Toner et al. Reents and colleagues, and Carrascal and his associates also demonstrated 34% and 45% of postoperative cognitive

8 60 impairment respectively. In most of the studies, postoperative cognitive impairment was seen in the domains of attention and concentration, psychomotor speed, reaction time, information processing, abstraction, and verbal and visual learning and memory. Studies with the inclusion of control group As a part of a prospective study of the neurological and neuropsychological complications of coronary artery bypass graft surgery, Shaw, Bates, and Cartilidge (1987) compared 235 patients undergoing heart surgery with a control group of 50 patients undergoing major surgery for peripheral vascular disease. The two groups were similar with respect to age, intellectual status, etc. A battery of 10 standard psychometric tests was administered to each patient two days prior to surgery. The tests chosen were Halstead reitan trail making test part B; information, orientation, mental control, logical memory and digit total, visual reproduction and associate learning subtests of the Wechsler memory scale (WMS); and the b lock design and vocabulary subtests of Wechsler adult intelligence scale (WAIS). Postoperative psychometric testing was performed approximately after one week in both surgical groups. Results revealed no significant difference in the mean preoperative scores for the two groups in any of the 10 psychometric tests. Postoperatively it was evidenced that 55% of the CABG patients developed mild neuropsychological deterioration, 19% developed moderate neuropsychological deterioration, and 4.7% developed severe deterioration. In the control group, 31% of the patients developed mild deterioration, but moderate or severe

9 61 intellectual dysfunction was not seen in the control group. The neuropsychological abilities that deteriorated most in CABG group were psychomotor speed, attention and concentration, new learning ability, and auditory short term memory. Kneebone, Andrew, Baker, and Knight (1998) attempted to determine the neuropsychological deficits after coronary artery bypass grafting surgery. Neuropsychological assessment was performed on 50 patients before, and seven days after coronary artery bypass grafting. From a matched control group of 24 normal subjects who were examined twice over a similar interval, reliable change indices that controlled for measurement error and practice effects were calculated for each neuropsychological measure. Tests carried out were Trail making Test A & B (attention, divided attention), Grooved pegboard (Left hand, Right hand, and both Right and Left hands simultaneously), Controlled oral word association test (verbal Fluency), Digit symbol substitution test, California verbal learning test, Boston naming test, and full scale intelligence quotient. Tests that were most sensitive to postoperative decline were Pegboard -right hand (42%), Digit symbol substitution Test (36%), Trail making test B (36%). The incidence of impairment was comparatively low on the memory measures. The least sensitive test was Controlled oral word association test. Fearn et al. (2001) compared cognitive functions in 70 patients undergoing CABG with 19 patients admitted for urologic procedures. A standardized, comprehensive, and computerized battery of tests was administered in all patients and control subjects. Tests included were Simple

10 62 reaction time, Choice reaction time, Number vigilance, Memory recall, Word recognition and Picture recognition. It was found that patients in the CABG group were faster and more accurate than control subjects preoperatively with significant differences in accuracy of memory, speed of picture recognition, overall attention, memory reaction time and accuracy. Postoperatively, patient s performance in the CABG group deteriorated significantly in most test performances of cognitive function like memory tests, accuracy of choice reaction time, and word recognition reaction time when compared with those of the urology control patients. They also examined the relationship between the number of embolic signals detected in the Middle Cerebral Artery during surgery and memory tests, and found a direct correlation between the number of emboli and the deterioration in accuracy of memory. Rosengart, Sweet, and Finnin (2005) evaluated cognitive dysfunction prior to surgery in patients referred for coronary artery bypass graft surgery (CABG) and compared with normal controls. Forty one cardiac patients and 41 healthy controls underwent neurocognitive testing like, Digit span and Digit symbol from Wechsler adult intelligence scale (WA IS), Grooved pegboard (Left hand, Right hand), Controlled oral word association test (verbal Fluency), Trail making test A & B (attention, divided attention), Stroop test (response Inhibition), Visual naming test, and Hopkins verbal learning test. The mean scores for 5 of the 14 different tests were significantly lower in cardiac patients compared with control group, and the five tests were Wechsler adult intelligence scale, Digit symbol (nonverbal memory deficit), the three components of the Hopkins verbal

11 63 learning test (verbal learning and memory deficit), and the controlled oral word association test (verbal Fluency). Forty six percentages of cardiac subjects would be considered to be impaired on three or more neuropsychological test performances compared with 29% of the controls. Ernest et al. (2006) studied both pre and post cognitive deficits in CABG candidates using both healthy control group, and published normative data. A battery of neuropsychological tests was administered to 109 patients listed for bypass surgery and cognitive function of bypass candidates was compared with that of a healthy control group (n=25). The tests involved were Rey auditory verbal learning test (immediate, recent, and delayed verbal memory), Reitan trail making test A & B (attention, divided a ttention), Grooved pegboard (motor speed), Digit span test of Wechsler memory scale (short term memory and working memory), Digit symbol test from Wechsler adult intelligence scale, Letter cancellation test (visual at tention, scanning), Controlled oral word association test (verbal Fluency), Boston naming test (language, naming) WMS- R visual reproduction (visual Memory), Judgment of l ine orientation (v isuospatial capacity), and Stroop color-word test (executive function). Results revealed that cognitive test scores of candidates for surgery were significantly lower than those of the control group on test performances of attention, information processing speed, and verbal memory. Bypass candidates showed significantly higher percentage of cognitive impairment on performances of Rey auditory verbal learning test, Digit symbol and Digit span tests.

12 64 Lewis, Maruff, and Silbert (2006) conducted a study to evaluate the cognitive dysfunctions using combinations of two to seven cognitive tests. Two hundred and four coronary artery bypass graft patients and 90 healthy nonsurgical controls aged 55 years or older completed a battery of cognitive tests at baseline (preoperative) and one week later (postoperative). Neuropsychological test battery consisted of Reitan trail making Test A & B (attention, divided attention), Grooved pegboard (dominant and n on- dominant hand), Controlled oral word association test (verbal Fluency), Digit symbol substitution test, and Word learning task from Consortium to Establish a Registry for Alzheimer s disease (CERAD). It was found that the average incidence of cognitive dysfunction progressively increased as the number of tests increased from two to seven tests in both the groups. The studies cited above however have recognized another very important factor when neuropsychological dysfunction after cardiac surgery is considered; that is, specifically the degree of cognitive impairment prior to operation. Rosengart et al. demonstrated with preoperative testing that, patients planning to undergo CABG had poorer cognitive function than normal controls. Similarly, Ernest et al. compared patients planning to undergo CABG with a group of control patients who had no cardiovascular risk factors. Preoperative cognitive testing revealed that patients had significantly lower cognitive function than the healthy control group. These preoperative neurocognitive changes, which clearly occur in a proportion of patients, are most likely related to a combination of factors that include atherosclerosis, cardiogenic embolism, hypoxia and

13 65 concurrent depression. The findings of these studies clearly evidenced the presence of neuropsychological deficits in the domains of psychomotor speed, attention and concentration, verbal fluency, information processing speed, short term memory and verbal and visual learning and memory among MI patients. Longitudinal studies measuring transient neurocognitive deficits following coronary artery bypass grafting surgery Rione (1993) studied prospectively the neuropsychological sequelae of MI and measured neuropsychological outcomes three months, and one year after MI in 155 patients. The detailed neuropsychological tests were Wechsler adult intelligence scale, Wechsler memory scale, Verbal learning test, Finger tapping test, Tests of executive function and Visual learning test. The main results of this study demonstrated the rapid initial improvement of cognitive functions after MI and the presence of mild neuropsychological deficits in the majority of survivors at one year. The most common neuropsychological sequelae in MI were the impairment of delayed memory. Bruggemans, VanDijk, and Huysmans (1995) assessed cognitive dysfunctioning following coronary artery bypass graft surgery. In this study, the confounding variables such as learning effects and effects of distress on test performances were controlled by including the spouse of patients, exposed to the same potential stress effects associated with the operation, as a nonsurgical control group. The experimental group consisted of 63 patients undergoing CABG. Neuropsychological tests assessing the domains of immediate memory, learning and recent memory, attention and psychomotor speed, and verbal

14 66 fluency was administered to both the groups two weeks preoperatively and one week, one month, and six months post-operatively. Results revealed significant impairments in patients in the test performances of recent memory, attention, psychomotor speed and verbal fluency. It was also found that memory functions showed sustained postoperative impairment. Vanninen, Aikia and Kononen (1998) conducted a study to analyze the frequency and severity of subclinical cerebral complications associated with coronary artery bypass grafting (CABG). A total of 38 patients undergoing elective CABG and 20 control patients undergoing other major vascular surgery were included in this study. They were assessed by MRI of the brain, QEEG and a neuropsychological test battery that evaluates cognitive functions in major areas known to be vulnerable to organic impairment (learning and memory, attention, flexible mental processing and psychomotor speed), approximately two days before surgery, and eight days and three months after surgery. The study revealed no decline in mean cognitive performance in any of the groups. Cognitive performance slightly improved in general, as can be expected on the basis of normal practice effect. They found that CABG causes more QEEG alterations and small ischemic cerebral lesions that are detectable by MRI than does other major vascular surgery, which are subclinical, because no statistically significant deterioration in mean neuropsychological test was detected. Borowicz et al. (2000) studied extensively the long term changes in cognitive performance after coronary artery bypass grafting surgery. A battery of

15 67 cognitive tests, assessing the domains of attention, language, memory, executive functions, visuo-construction, psychomotor and motor speed, was administered pre-operatively, at one month, one year, and upto five years postoperatively. It was observed that long term decline was seen in psychomotor speed and visuo-construction, while improvement was seen in executive functions. Late decline was seen in all cognitive domains except attention and executive functions. The significant late decline raised the possibility that the patient population may be at risk for cognitive problems in future. Newman et al. (2001) examined the course of cognitive change during five years after CABG and the preoperative decline on long term cognitive function. In 261 patients who underwent CABG, neurocognitive tests were performed pre-operatively, before discharge, and six weeks, six months, and five years after CABG surgery. The cognitive tests used were Digit symbol test, Trail making test, Digit span test (attention, psychomotor processing speed, and concentration), Benton visual retention test (visual memory, visuo -spatial orientation), and Randt short- story memory test (abstraction, verbal memory, and language comprehension). Among the patients studied, the incidence of cognitive decline was 53 percent at discharge, 36 percent at six weeks, 24 percent at six months, and 42 percent at five years and the results confirmed persistence of cognitive decline after CABG. Bergh, Backstorm, Jonsson, Havinder, and Johnsson (2002) investigated the MI patients and their spouses perceptions of cognitive functioning one to two years after coronary artery bypass grafting surgery. Seventy-six married

16 68 patients who had undergone CABG were completed interviews and assessments in memory, concentration, general health, social functioning, and emotional state. It was found that memory was the only scale in which spouses reported significant deterioration. Zimpfer, Czerny, and Vogt (2004) evaluated long-term neurocognitive deficits after CABG and compared the findings with nonsurgical controls to elucidate factors associated with long-term neurocognitive deficit. Hundred and four patients undergoing CABG and 80 nonsurgical controls participated in the study. After CABG, neurocognitive function was serially evaluated at one week (n=104), fourth month (n=100), and third year follow up (n=88). Neurocognitive function was objectively measured by means of Trail making test A and Mini mental status examination. Results revealed that 51.3% of the patients at seventh day, 48.8% of patients at fourth month, and 50.0% of patients at third year follow up showed neuropsychological deficits, and it was concluded that CABG causes long-term neurocognitive deficit. Whitaker et al. (2004) conducted a study in 198 patients scheduled for elective CABG surgery in the department of cardiothoracic surgery at the Middlesex hospital, London to test the intraoperative microembolic load to the brain and the neuropsychological sequelae in patients undergoing CABG surgery. A neuropsychological test battery of nine tests was administered in 192 patients, two days before surgery and 6-8 weeks later during a routine clinic. The battery consisted of Rey auditory verbal learning test, Trail making test A and B, Grooved pegboard, Symbol digit replacement test, Non-verbal memory,

17 69 Letter cancellation and Choice reaction time. It was observed that there were no differences in the neuropsychological test scores pre- and post-operatively. At six weeks post-surgery, there was a trend towards greater improvement in neuropsychological performance. Patients also showed better performance in all the tests of the battery apart from the Non-verbal memory test. Selnes et al. (2007) studied late cognitive decline after coronary artery bypass graft surgery by comparing the changes in cognitive performance from baseline to three years in patients undergoing CABG (n=227) with coronary heart patients but no surgery (n=99) and heal thy controls (n=69). Neuropsychological performances were assessed by standardized tests of attention, language, verbal and visual memory, visuospatial ability, executive functions, and psychomotor and motor speed at baseline, and at 36 months. It was observed that post-operatively, the surgical group had significantly lower performance at 36 than 12 months for the domains of verbal memory, visual memory, and visuo-construction. For the non-surgical cardiac controls, the decline from 12 to 36 months was statistically significant in all except the domains of executive functions and psychomotor speed. For the healthy control group, there was a trend towards mild decline in all the test performances which reached statistical significance only for the domains of visual memory and attention. The results established a mild but nonsignificant trend toward late postoperative cognitive decline in both the surgical and non-surgical control groups compared to the healthy control group.

18 70 Knipp et al. (2008) investigated the course of cognitive performance during three years after surgery. Thirty-nine patients undergoing CABG completed preoperative neuropsychological examination and were followed up prospectively at discharge, three months, and three years after surgery. Cognitive performance was assessed with a battery of standardized psychometric tests like Trail making test B (executive function), Zimmermann joint attention test (attention), Trail making t est A (psychomotor speed), Verbal learning test (immediate and delayed verbal memory), Corsi block tapping test (visual memory), Horn performance test (logical thinking and visuoconstruction), Digit span test from Wechsler memory scale (short - term memory). Postoperative cognitive deficits were observed in 56% of the patients at the time of hospital discharge, in 23% at three months and in 31% at three years. Between baseline and at discharge test performances, there were statistically significant decline in executive function, attention, verbal learning, visual memory, short-term memory, logical thinking, and visuo-construction. The test performances between discharge and at three months showed that cognitive test scores were improved in general. Comparing cognitive performances at three months and at three year follow-up with baseline performances, scores did not differ for most test performances, except for verbal memory. Results indicated a two-stage course of cognition after CABG characterized by early decline and subsequent improvement followed by late decline. The main focus of the studies reported above was to look at the transient cognitive deficits in MI patients before and after surgery. Many researchers have

19 71 focused on the long term course and prognosis of cognitive deficits in MI patients following surgery, the factors associated with favorable prognosis as well as the relationship of cognitive deficits to the overall prognosis of the patient. The initial study by Newman suggested that long term neuropsychological dysfunction was associated in a significant number of patients who had undergone cardiac surgery. A similar study was reported by Selnes and his associates. This longitudinal study compared patients who underwent cardiac surgery, and non-surgical cardiac control group that comprised patients with coronary artery disease and healthy control group. Both patient groups were matched for similar risk factors. The study demonstrated that neurocognitive outcomes in patients who underwent surgery did not differ from those in comparable control group without surgery both at one and three years. As reported, both the groups showed mild but statistically non significant decline between one and three years. These findings suggested that the long term cognitive deficits in patients with coronary artery disease and following surgery is due to the presence of cerebral vascular risk factors and aging rather than due to the operation itself. The results of these studies revealed significant impairments in patients for recent memory, attention, psychomotor speed, and verbal fluency. It was also found that memory functions showed sustained postoperative impairment. It is seen that a small percentage of the patients improve, while others remain stable or are seen to worsen. Deterioration was seen to be associated with older age, cognitive impairment before surgery and presence of cardiovascular risk factors.

20 72 Studies related to short-term and long-term neuropsychological outcomes in on-pump versus off-pump coronary surgery Diegeler et al. (2000) investigated the neuropsychological outcomes in MI patients who underwent coronary artery bypass operation without cardiopulmonary bypass (off-pump CABG) in comparison with the conventional procedures using cardiopulmonary bypass (CPB). Forty patients were examined preoperatively and postoperatively using Syndrom Kurz Test (SKT), a rating scale consisting of nine consecutive subtests to examine performance in cognitive functions of memory and attention. The cognitive scores showed a homogenous decrease in CPB group compared to the off- pump group. Ninety percentage of the patients in the CPB group showed pathologic score. The study demonstrated significant differences between on-pump and off-pump coronary surgery regarding neuropsychological outcomes and this finding confirmed the association between cerebral micro-emboli and impairment in postoperative cognitive tests. Stroobant, Nooten, Belleghem, and Vingerhoet (2002) examined the frequency of neuropsychological abnormalities occurring in patients undergoing CABG with (on -pump) and without (off -pump) cardiopulmonary bypass by administering a battery of seven standardized neuropsychological tests such as Rey auditory verbal learning test (AVLT ) assessing verbal memory, Trail making test (TMT) assess ing speed for visual search, attention and mental flexibility, Grooved pegboard test assessing finger and hand dexterity, Block tap test assessing nonverbal immediate memory and attention, Line bisection test

21 73 (LBT) assessing unilateral visual inattention, Controlled oral word association test (COWAT) assess ing word fluency and Judgment of line orientation (JLO) assessing angular relationship between line segments. Results revealed that there was no significant difference between the on-pump and off-pump groups in post-operative neuropsychological performance soon after surgery. A significant difference was found in the neuropsychological performances between the two groups six months after surgery, with more favorable results for the off-pump group. Individual comparisons revealed that 59% of the patients of both the groups undergoing CABG showed evidence of cognitive impairment soon after surgery. In 11% of the patients (all on pump), the cognitive dysfunctions persisted at follow-up. The difference in cognitive failures between on-pump and off-pump CABG patients was examined by Keizer, Hijman, Dijk, Kalkman, & Kahn (2003). In this study, the Cognitive failures questionnaire (CFQ) w as assigned preoperatively and one year postoperatively to 81 patients who were undergoing off-pump (n=45) or on -pump (n=36) CABG. There was no difference between on-pump and off-pump CABG groups in cognitive performances and the study suggested that CABG will not result in cognitive decline. Lund et al. (2005) conducted a study to compare off-pump and on-pump coronary artery bypass grafting surgery with regard to the frequency of new postoperative cerebral ischemic lesions and the prevalence of postoperative cognitive impairments. Hundred and twenty patients were examined with extensive neuropsychological tests such as Rey auditory verbal learning test

22 74 (AVLT) assessing verbal memory, Trail Making Test (TMT) assessing speed for attention and mental flexibility, Grooved pegboard test assessing motor coordination, Digit symbol, Digit span, Similarities and Block design from WAIS- R and Controlled word association test, both before and after surgery. It was revealed that there were no significant differences between on-pump and offpump surgery patients with regard to new postoperative cerebral lesions. The prevalence of cognitive impairment after surgery was also similar in the two groups (3 months - off-pump 20.4%, on-pump 23.1%; 12 months - off-pump 24.1%, on-pump 23.1%). It was concluded that performances in neuropsychological tests were similar after off-pump and on-pump coronary artery bypass grafting surgery. Cognitive outcomes in off-pump and on-pump patients at two and six months after surgery were examined and compared by Ernest et al. (2006). Cognitive function was assessed using 11 standardized cognitive tests, covering a variety of domains such as verbal memory, motor capacity, attention, information processing speed, working memory, visual attention, scanning, verbal fluency, language, naming, visual memory, visuospatial capacity, and executive functions. It was revealed that in terms of cognitive impairment there was no significant difference between the off-pump and the on-pump groups in cognitive test scores or incidence of cognitive impairment at two or six months, with the exception that fewer off-pump patients showed impairment on one test of verbal fluency at six months. When the pattern of cognitive changes over time

23 75 between the two groups was compared, only in verbal fluency, the off pump group showed more rapid post surgical gains than the on- pump group. Motallebzadeh, Bland, Markus, Kaski, and Jahangiri (2007) examined the difference in postoperative neurocognitive functions between patients undergoing off-pump and on-pump coronary artery bypass surgery (CABG). Two hundred and twenty patients admitted for CABG were randomly selected. There were 104 on-pump surgery patients and 108 off-pump surgery patients. Neuropsychological tests such as Complex figure test, Grooved peg board test, Rey auditory verbal learning test, Letter cancellation test, Trail making test, Symbol digit modalities test and Verbal fluency test were administered at one week before surgery, before discharge from hospital, at six weeks after surgery and six months after surgery. It was demonstrated that at discharge from hospital, neurocognitive function was better after off-pump surgery, possibly as a result of the lower embolic load. The difference in neurocognitive functions did not persist at six weeks and six months. The above studies have looked at the significant difference in neuropsychological outcomes between off-pump patients and those patients who underwent conventional CABG with CPB. Some studies showed instances of better cognitive outcomes in the off-pump group on certain tests, at certain points, or when certain statistical methods were used. Motallebzadeh reported better cognitive outcomes in the off-pump group. Diegeler investigated neuropsychological outcomes in patients who underwent coronary artery bypass operation without cardiopulmonary bypass (off-pump CABG) in comparison with

24 76 the conventional procedures using cardiopulmonary bypass (CPB). It was estimated that 90% of the patients in the CPB group showed pathologic score compared to the off-pump CABG. Some studies showed no differences between off-pump and on-pump groups in terms of short term and long term cognitive outcomes. Keizer and associates found no difference between on-pump and off-pump CABG patients. Similarly Ernest compared cognitive outcomes in off-pump and on-pump patients at two and six months after surgery, and it was revealed that in terms of cognitive impairment there was no significant difference between the off-pump and the on-pump group in cognitive test scores or incidence of cognitive impairment at two or six months. Therefore, a clear cognitive advantage for the off-pump surgical technique has not been convincingly demonstrated. Traditionally, most neuropsychological complications after on-pump bypass surgery are thought to be due to cerebral hypoperfusion or emboli related cerebrovascular damage secondary to cardiopulmonary bypass (CPB). Studies related to Type A coronary prone behavior and myocardial infarction The Type A construct was first propounded by Friedman and Rosenman (1974). The Type A behavior pattern is viewed as an aroused state superimposed upon a complex underlying substrate of interrelated factors. Type A persons were illustrated as people with a highly competitive desire for achievement and recognition, together with a tendency towards hostility and

25 77 aggression, and a sense of immense time urgency and impatience (Rosenman & Friedman). Several theoretical explanations or models could account for the demonstrated association between Type A behavior and myocardial diseases. The first and simplest model assumes that Type A behavior leads to MI, presumably through stress related autonomic neuroendocrine (physiologic) mechanism. This model implies that successful modification of Type A behavior should relieve the pathophysiologic forces that can act upon the coronary vasculature to produce heart diseases. Blumenthal, Williams, Kong, Schanberg, and Thompson (1978) evaluated 156 patients referred for diagnostic coronary angiography to determine the association between Type A behavior pattern and myocardial infarction. Patients were assessed on the basis of a structured interview technique developed by Friedman and Rosenman and assigned a rating of Type A, Type B, or Type X (indeterminate). Results showed that Type A behavior pattern was found related to atherosclerosis, which is the main cause of myocardial infarction. Haynes, Feinleib, and Kannel (1980) studied the relationship of psychosocial factors to coronary heart disease and administered a 300-item psychosocial questionnaire to 1,674 coronary-free individuals aged between 45 and 77 years. The participants were followed for the development of coronary heart disease (CHD) over 8 y ears. Females who developed CHD scored significantly higher on Type A behavior, suppressed hostility, tension, and anxiety than those remaining free of CHD. Type A behavior and suppressed

26 78 hostility were independent predictors of CHD incidence when controlled for standard coronary risk factors and other psychosocial factors. Males exhibiting Type A behavior, work overload, suppressed hostility, and frequent job promotions were at increased risk of developing CHD, especially in the years old age group. Type-A behavior was associated with a two-fold increase in the risk of CHD in males and females aged years. This association was found only among white-collar workers and was also independent of the standard coronary risk factors and other psychosocial factors. Results suggested that Type-A behavior and suppressed hostility may be involved in the pathogenesis of CHD in both sexes. Waltz, Bandura, Bernhard, Kaufhold, and Lehman (1988) investigated correlates of Type A behavior pattern, cognitive and emotional outcomes, in a representative sample of 1,000 cardiac patients (aged <60 years). It was found that Type A subjects have unfavorable health and social situations, and they adjusted less well to the stress syndrome triggered by myocardial infarction. Van-Doornen (1980) tested the hypothesis that psychophysiological features of the coronary risk personality (CRP) are clearly discernable before myocardial infarction (MI) occurs. Psychological test assessments were obtained from 46 male MI patients (mean age 47 years) and 78 healthy controls (mean age 40 years), who were classified as either high or low risk on blood pressure, serum cholesterol, and/or smoking measures. It was found that the crucial features of the coronary risk personality appeared to be the impatience and activity dimensions of Type A behavior.

27 79 Wrzesniewski, Zyzanski, and David ( 1980) administered the Jenkins Activity Survey to 316 polish citizens with myocardial infarction, rheumatics, and healthy controls. The data obtained were compared with those from 609 US recovered coronary patients and healthy controls. The results revealed that Type A behavior exists within the Polish culture, and it has the same relation with coronary heart disease as found in the US. Byrne (1981) hypothesized that persons characterized by Type A behavior pattern organize lifestyles to increase the probability of encountering stressful events. Hundred and twenty survivors of MI (mean age y ears) were compared with 40 normal coronary patients. Significant correlations were found between measures of Type A behavior and both reported frequency of stressful events and estimates of the impact of these emotional events. Saon, Jenny, and Amaro (1982) examined the relationship between the Type A coronary behavior pattern and the psychological characteristics of infarct patients, and compared the incidence of Type A behavior in 25 male patients (age years) who had suffered a heart attack (experiment group) and 25 age-matched male patients who had no evident cardiac pathology (control group). All patients were interviewed and tested on the following behavioral characteristics: competitiveness and stress in attaining objectives, work goals and compromises, haste and impatience, hostility, irritability, and degree of relaxation. Type A personality was found in 88% of the patients who had suffered heart attack and in none of the control group.

28 80 Corse (1982) investigated coronary-prone behavior pattern and cardiovascular response in persons with and without coronary heart disease. Measures of heart rate and systolic and diastolic blood pressure were obtained from 24 males with coronary heart disease (CHD) (mean age 51.3 y ears) and 34 males without it (mean age 49.1 y ears) during a baseline period and while patients performed a series of difficult and frustrating cognitive tasks. Each patient was also administered a structured interview for Type A/Type B assessment and the Jenkins Activity Survey. Results indicated that independent of the A/B typology, CHD patients experienced significantly greater diastolic blood pressure elevations during the experimental tasks than did the non-chd controls. Type A's exhibited greater task-related increases in the systolic and diastolic blood pressure than did Type B's, but changes in heart rate did not differ between the two groups. Overall, the results were consistent with the hypothesis that heightened cardiovascular reactivity under stress may mediate relationships between behavioral factors and CHD. Kahn (1982) examined the association between Type A personality and coronary heart disease (CHD). Five aspects of Type A behavior were assessed in 53 patients undergoing routine stress tests with concomitant thallium-201 myocardial perfusion studies. Severity of CHD was estimated on a 4-point scale. Pearson correlation coefficients were separately computed for patients with and without reported history of myocardial infarction. For 37 patients without reported MI (age years), CHD severity was significantly correlated with overall Type A, vocal characteristics, job involvement, and aggressiveness, but

29 81 not with time urgency. For the 16 patients with reported MI (mean age 53.1 years), CHD severity was significantly correlated with job involvement only. Data are consistent with the association of Type A personality and coronary pathogenesis, but may also reflect Type A psychological and physiological characteristics. Falger (1983) investigated 103 male myocardial infarction patients and 101 healthy controls with respect to Type A coronary-prone behavior pattern. Patients were divided into 3 age cohorts: years, years, and years. The results indicated that Type A behavior was generally twice as prevalent in the patient group compared to the control group. In the youngest cohort of patients, however, prevalence of Type A behavior was 4:1. In the older cohorts, ratios were 2:1 and 1:1 for patients and healthy controls respectively. In all cohorts, infarction patients scored significantly higher on a measure of vital exhaustion and depression prior to myocardial infarction than controls. Except in the oldest cohort, the life course of myocardial infarction patients was characterized by a specific pattern of exposure to socially desirable life changes, both in the work/career and the family/social life domains. The most definite life changes observed were unemployment, educational problems with one's children, and serious or prolonged marital conflicts. Koller, Prilhofer, Haider, and Groll-Knapp (1988) explored a broad spectrum of risk factors, risky behaviors, and life conditions that are known to increase the risk of coronary heart disease (CHD) in men to see if these

30 82 variables were equally represented in 47 female CHD patients. Type A behavior was not more predominant in female CHD patients than in male CHD patients. Ghulam, Gupta, Bandyopadhyaya, and Mishra (1990) investigated behavior patterns in 75 patients with coronary heart disease and in 75 matched healthy controls. To measure Type A/B behavior, patients completed the Bortner Rating Scale ( Bortner, 1969). Subjects with heart disease had significantly higher scores and suffered more often with Type A behavior pattern as compared with controls. A significant correlation was also observed between Type A behavior and myocardial infarction. No significant correlation was found between Type A behavior and age, sex, hypertension, or parental history of coronary heart disease. Jarvinen and Raikkonen (1990) investigated Type A factors related to the level of somatic risk factors of coronaryc heart disease in 1,209 healthy adolescents and young adults. Subjects were clinically examined three times within a six years follow-up period. Risk and nonrisk groups were constructed on the basis of risk levels over three testings, separately in each somatic risk variable. Type A behavior was evaluated using a questionnaire based on the Jenkins Activity Survey. Of the Type A factors, hard-driving had the strongest association with the somatic risk level. Aggression competitiveness was also related to the risk but not very strongly. Impatience was of no importance while engagement involvement was likely to be a protective factor. Kaushik, Mukhopadhyay, Sheik, and Sunil (1991) compared the psychological and physical correlates of coronary heart disease (CHD) in 15

31 83 male and 9 female CHD patients (30 55 years old) and 45 matched controls using the Jenkins Activity Survey. Psychological correlates of coronary prone behavior, job involvement, speed and impatience, hard-driving and stressful life events were examined. Physical correlates like weight, height, and systolic and diastolic blood pressure were also examined. The results showed that the important precipitating factor for both the male and the female CHD patients is Type A personality pattern. Only the hard driving factor indicated a significantly higher mean in the female CHD patients. Male CHD patients had more dominant roles in stressful events, higher weight, greater height, and higher systolic and diastolic blood pressure than either female CHD patients or controls. Wright (1992) evaluated the physical and Type A behavior pattern risk factors for heart disease. Scores of 40 male patients hospitalized for coronary heart disease on 11 factors of Type A behavior pattern and seven physical CHD risk factors were compared with the scores obtained by 40 male patients who were not diagnosed as CHD. All patients were years old. Family history for CHD was the only physical risk factor for which a significant difference was found. CHD patients scored significantly higher on all the seven interviewmeasured Type A and Type A subcomponent variables. Only two of the four Jenkins Activity Survey-measured Type A variables produced significant differences (hard driving; competitiveness) with higher mean scores for CHD patients.