Self-reported Lifestyle Activities in Relation to Longitudinal Cognitive Trajectories.

BACKGROUND: Few studies have examined the relationship between lifestyle activity engagement and cognitive trajectories among individuals who were cognitively normal at baseline. OBJECTIVE: To examine the relationship of current engagement in lifestyle activities to previous cognitive performance among individuals who were cognitively normal at baseline, and whether this relationship differed for individuals who subsequently developed mild cognitive impairment (MCI), or by APOE-4 genotype, age, and level of cognitive reserve. METHODS: Participants (N=189) were primarily middle-aged (M=56.6 y) at baseline and have been prospectively followed with annual assessments (M follow-up=14.3 y). Engagement in physical, cognitive, and social activities was measured by the CHAMPS activity questionnaire. Longitudinal cognitive performance was measured by a global composite score. RESULTS: Among individuals who progressed to MCI (n=27), higher lifestyle activity engagement was associated with less decline in prior cognitive performance. In contrast, among individuals who remained cognitively normal, lifestyle activity engagement was not associated with prior cognitive trajectories. These effects were largely independent of APOE-4 genotype, age, and cognitive reserve. CONCLUSIONS: Greater engagement in lifestyle activities may modify the rate of cognitive decline among those who develop symptoms of MCI, but these findings need to be confirmed in prospective studies.

Perioperative Low Arterial Oxygenation Is Associated With Increased Stroke Risk in Cardiac Surgery.

BACKGROUND: Both patient characteristics and intraoperative factors have been associated with a higher risk of stroke after cardiac surgery. We hypothesized that poor systemic oxygenation in the perioperative period is associated with increased risk of stroke following cardiopulmonary bypass. METHODS: In this study of 251 adult patients who underwent cardiopulmonary bypass procedures at a single center from 2003 to 2006, cases (patients with a postoperative stroke at least 24 hours after surgery) were matched 1:2 to controls without stroke. Minimum and average partial pressure of oxygen in arterial blood (PaO2) values, from arterial blood gas values during and up to 24 hours after surgery, were evaluated as continuous and categorical predictors. Conditional logistic regression models adjusted for potential confounders (demographics, comorbidities, and intraoperative variables) were used to evaluate associations between PaO2 variables and stroke status. RESULTS: Lower nadir PaO2 values were associated with postoperative stroke, with estimated odds of stroke increasing over 20% (adjusted odds ratio [OR], 1.23; 95% confidence interval [CI], 1.07-1.41) per 10 mm Hg lower nadir PaO2, and similarly increased odds of stroke per lower quartile of nadir PaO2 (OR, 1.60; 95% CI, 1.19-2.16). When average PaO2 was considered, odds of stroke was also increased (adjusted OR, 1.39 per lower quartile of mean PaO2; 95% CI, 1.05-1.83). Having a nadir PaO2 value in the lowest versus any other quartile was associated with an estimated 2.41-fold increased odds of stroke (95% CI, 1.22-4.78). Quartile of nadir but not average PaO2 results remained significant after adjustment for multiple comparisons. CONCLUSIONS: Odds of stroke after cardiac surgery are increased in patients with a low minimum PaO2 within 24 hours of surgery. Results should be validated in an independent cohort. Further characterizing the underlying etiology of hypoxic episodes will be important to improve patient outcomes.

The BIOCARD Index: A Summary Measure to Predict Onset of Mild Cognitive Impairment.

BACKGROUND: Changes in neuropsychological testing, neuroimaging, and cerebrospinal fluid may precede mild cognitive impairment (MCI). However, these markers are not routinely performed in outpatient clinical visits. OBJECTIVE: To evaluate whether a simple clinical index, consisting of questions given to patients and their informants, could predict the onset of symptoms of MCI among cognitively normal individuals. MATERIALS AND METHODS: Two hundred twenty-two participants in the BIOCARD study received a detailed history, physical examination, and neuropsychological testing annually. An index was calculated by including questions about memory problems, depression, age, education, history of cerebrovascular disease risk factors, and brain injury, family history of dementia, and the Mini-Mental State examination score. Cox regression analyses were used to determine if this index score was related to diagnosis of MCI. RESULTS: The BIOCARD Index score mean for individuals who progressed to MCI was 20.3 (SD=2.9), whereas the score for individuals who remained normal was 24.8 (SD=2.3) (P<0.001) [hazard ratio, SE for subsequent diagnosis of MCI=0.75 (0.67 to 0.84); P<0.001]. CONCLUSIONS: Lower BIOCARD Index score predicted symptoms of MCI several years before the MCI diagnosis. The BIOCARD Index can be easily used in clinics to identify cognitively normal older individuals who are at risk for deterioration.

Postoperative blood urea nitrogen is associated with stroke in cardiac surgical patients.

BACKGROUND: This case-control study identified perioperative risk factors associated with postoperative stroke risk after all cardiac surgical procedures. METHODS: Among 5498 adults 18 to 90 years old who underwent cardiac surgical procedures from 2005 to 2010, we identified 180 patients who suffered a stroke within 10 days postoperatively. Controls were randomly selected and frequency matched for sex and age-band to cases. Univariate and multivariate logistic regression analyses were performed to ascertain risk factors for postoperative stroke. RESULTS: Emergency surgical procedures (odds ratio [OR], 3.04; 95% confidence interval [CI], 1.80 to 5.10), current smoking (OR, 1.97; 95% CI, 1.29 to 3.00), peripheral vascular disease (OR, 2.80; 95% CI, 1.41 to 5.53), and previous stroke with residual paralysis (OR, 4.27; 95% CI ,1.18 to 15.38) were associated with increased stroke risk. Preoperative blood pressures were higher in patients with cases than in controls (p < 0.0001). Log of immediate postoperative blood urea nitrogen (BUN) was higher in patients with cases than in controls (p < 0.0001). In adjusted multivariable logistic regression, postoperative BUN was associated with increased odds of stroke (OR, 2.37 per 25% increase in BUN, p < 0.0001). Postoperative stroke risk was also predicted by emergency surgical procedures (OR, 2.70, p = 0.014), current smoking (OR, 2.82, p = 0.002), and preoperative diastolic blood pressure (DBP) (OR, 1.77 for every 10-point increase in DBP, p < 0.0001). Receiver operator characteristic curves indicated that postoperative BUN (area under the curve, 0.855) largely explained the increased postoperative stroke risk. CONCLUSIONS: In these analyses, we identified BUN as a marker of heightened postoperative stroke risk after cardiac surgical procedures. Postoperative risk markers may improve assessment of delayed postoperative strokes.

Cognitive changes preceding clinical symptom onset of mild cognitive impairment and relationship to ApoE genotype.

BACKGROUND: This study had two goals (1) to evaluate changes in neuropsychological performance among cognitively normal individuals that might precede the onset of clinical symptoms, and (2) to examine the impact of Apolipoprotein E (ApoE) genotype on these changes. METHODS: Longitudinal neuropsychological, clinical assessments and consensus diagnoses were completed prospectively in 268 cognitively normal individuals. The mean duration of follow-up was 9.2 years (+/- 3.3). 208 participants remained normal and 60 developed cognitive decline, consistent with a diagnosis of MCI or dementia. Cox regression analyses were completed, for both baseline scores and rate of change in scores, in relation to time to onset of clinical symptoms. Analyses were completed both with and without ApoE-4 status included. Interactions with ApoE-4 status were also examined. RESULTS: Lower baseline test scores, as well as greater rate of change in test scores, were associated with time to onset of clinical symptoms (p<0.001). The mean time from baseline to onset of clinical symptoms was 6.15 (+/- 3.4) years. The presence of an ApoE-4 allele doubled the risk of progression. The rate of change in two of the test scores was significantly different in ApoE-4 carriers vs. non-carriers. CONCLUSIONS: Cognitive performance declines prior to the onset of clinical symptoms that are a harbinger of a diagnosis of MCI. Cognitive changes in normal individuals who will subsequently decline may be observed at least 6.5 years prior to symptom onset. In addition, the risk of decline is doubled among individuals with an ApoE-4 allele.

Length of red cell unit storage and risk for delirium after cardiac surgery.

BACKGROUND: The time that red cell units are stored before transfusion may be associated with postoperative complications, although the evidence is conflicting. However, the association between the length of red cell unit storage and postoperative delirium has not been explored. We hypothesized that the length of storage of transfused red cell units would be associated with delirium after cardiac surgery. METHODS: We conducted a case-control study in which patients undergoing coronary artery bypass, valve, or ascending aorta surgery with cardiopulmonary bypass at Johns Hopkins from 2005 to 2011 were eligible for inclusion. Patients were excluded if they did not receive red cell units, received >4 red cell units during hospitalization, received any transfusion after the first postoperative day, or received red cell units that were not exclusively stored for ≤14 days or >14 days. Eighty-seven patients met transfusion-related inclusion criteria and developed postoperative delirium. Controls who did not develop delirium were selected from the same source population of eligible patients and were matched 1:1 based on age (± 5 years), 2- to 2.5-year band of date of surgery, and surgical procedure. For each patient, we calculated the average storage duration of all transfused red cell units. The primary outcome was odds of delirium in patients who were transfused red cell units with exclusive storage duration >14 days compared with that of ≤14 days. Secondary outcomes were odds of delirium with each increasing day of average red cell unit storage duration. We used conditional multivariable regression to test our hypotheses. RESULTS: In conditional multivariable analysis of 87 case-control pairs, there was no difference in the odds of patients developing delirium if they were transfused red cell units with an exclusive storage age >14 days compared with that ≤14 days (odds ratio [OR] 1.83; 95% confidence interval, 0.73-4.58, P = 0.20). Each additional day of average red cell unit storage beyond 14 days was associated with a 1.01- to 1.13-fold increase in the odds of postoperative delirium (OR, 1.07; P = 0.03). Each additional day of average storage beyond 21 days was associated with a 1.02- to 1.23-fold increase in the odds of postoperative delirium (OR, 1.12; P = 0.02). CONCLUSIONS: Transfusion of red cell units that have been stored for >14 days is not associated with increased odds of delirium. However, each additional day of storage >14 or 21 days may be associated with increased odds of postoperative delirium in patients undergoing cardiac surgery. More research is needed to further characterize the association between delirium and storage duration of transfused red cell units.

The role of head computed tomography imaging in the evaluation of postoperative neurologic deficits in cardiac surgery patients.

BACKGROUND: Computed tomography (CT) scans of the head without contrast are routinely obtained to evaluate neurologic deficits after cardiac surgery, but their utility is unknown. We evaluated our experience with this imaging modality to determine its value. METHODS: We retrospectively identified cardiac surgery patients with postoperative neurologic deficits occurring during the first week after surgery between January 2000 and December 2012. Stroke was defined by neurologist's determination, whereas a nonfocal deficit (NFD) was defined by the presence of seizure, delirium, or cognitive impairment. We defined early noncontrast head CT as occurring within 7 days of surgery. Outcomes included positive findings on CT, in-hospital mortality, and length of stay. Multivariate logistic regression identified predictors of positive findings on head CT. RESULTS: Within the population of 11,070 postoperative patients, 451 had early noncontrast head CT scans (4%). Two hundred two (44.7%) were associated with stroke, and 249 (55.2%) were associated with NFD. Among stroke patients, 40 of 202 (20%) showed acute infarction, 17 of 202 (8%) showed subacute infarction, and 5 of 202 (2%) showed hemorrhage. Among NFD patients, 1 of 248 (0.4%) showed acute infarction, 4 of 248 (1.6%) showed subacute infarction, and 1 of 248 (0.4%) showed hemorrhage. There was no difference in in-hospital mortality (stroke, 42 of 201 [21%] versus NFD, 41 of 248 [16%]; p = 0.2) or length of stay (stroke, 24 d versus NFD, 22 d; p = 0.5). On multivariable logistic regression, only focal deficits and aortic procedures predicted a positive finding on CT scan. CONCLUSIONS: This study reviewed the utility of early postoperative noncontrast head CT in cardiac surgery patients. With focal neurologic deficits, this imaging modality was positive for approximately one third of patients, but rarely positive for NFD. Its use in this setting has limited utility.

Intraoperative hemoglobin levels and transfusion independently predict stroke after cardiac operations.

BACKGROUND: Anemia has been associated with adverse cerebrovascular outcomes, particularly after cardiac operations. This study was conducted to determine if hemoglobin levels during and after cardiopulmonary bypass (CPB) predict postoperative stroke in cardiac surgical patients, independent of transfusion requirements. METHODS: Individuals who had sustained a clinical postoperative stroke (cases) were matched 1:2 with controls by age, sex, surgical procedure, and year of operation. In 617 patients, conditional logistic regression was performed to analyze associations between hemoglobin levels before and after CPB, and stroke. RESULTS: After adjustment for potentially confounding vascular risk factors, lower hemoglobin after CPB was associated with a higher risk of stroke, even after adjustment for the amount of packed red blood cells transfused (adjusted odds ratio, 1.28; 95% confidence interval, 1.00 to 1.64, per point of lower hemoglobin level; adjusted odds ratio for stroke per higher quartile of packed red blood cells transfused in this model, 1.37; 95% confidence interval, 1.02 to 1.83). Similar associations were not found for hemoglobin concentrations preoperatively nor change in hemoglobin from before to after CPB. A post-CPB hemoglobin level below the median was associated with 37% increased odds of a postoperative stroke occurring (p = 0.02). CONCLUSIONS: Lower postoperative hemoglobin levels and higher intraoperative transfusion requirements are each independently associated with a higher risk of stroke. Reduced cerebral oxygen delivery due to anemia may contribute to cerebral injury after coronary artery bypass grafting.

Association between hypotension, low ejection fraction and cognitive performance in cardiac patients.

BACKGROUND AND PURPOSE: Impaired cardiac function can adversely affect the brain via decreased perfusion. The purpose of this study was to determine if cardiac ejection fraction (EF) is associated with cognitive performance, and whether this is modified by low blood pressure. METHODS: Neuropsychological testing evaluating multiple cognitive domains, measurement of mean arterial pressure (MAP), and measurement of EF were performed in 234 individuals with coronary artery disease. The association between level of EF and performance within each cognitive domain was explored, as was the interaction between low MAP and EF. RESULTS: Adjusted global cognitive performance, as well as performance in visuoconstruction and motor speed, was significantly directly associated with cardiac EF. This relationship was not entirely linear, with a steeper association between EF and cognition at lower levels of EF than at higher levels. Patients with low EF and low MAP at the time of testing had worse cognitive performance than either of these alone, particularly for the global and motor speed cognitive scores. CONCLUSIONS: Low EF may be associated with worse cognitive performance, particularly among individuals with low MAP and for cognitive domains typically associated with vascular cognitive impairment. Further care should be paid to hypotension in the setting of heart failure, as this may exacerbate cerebral hypoperfusion.

Delirium after coronary artery bypass graft surgery and late mortality.

OBJECTIVE: Delirium is common after cardiac surgery, although under-recognized, and its long-term consequences are likely underestimated. The primary goal of this study was to determine whether patients with delirium after coronary artery bypass graft (CABG) surgery have higher long-term out-of-hospital mortality when compared with CABG patients without delirium. METHODS: We studied 5,034 consecutive patients undergoing CABG surgery at a single institution from 1997 to 2007. Presence or absence of neurologic complications, including delirium, was assessed prospectively. Survival analysis was performed to determine the role of delirium in the hazard of death, including a propensity score to adjust for potential confounders. These analyses were repeated to determine the association between postoperative stroke and long-term mortality. RESULTS: Individuals with delirium had an increased hazard of death (adjusted hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.38-1.97) up to 10 years postoperatively, after adjustment for perioperative and vascular risk factors. Patients with postoperative stroke had a HR of 2.34 (95% CI, 1.87-2.92). The effect of delirium on subsequent mortality was the strongest among those without a prior stroke (HR 1.83 vs HR 1.11 [with a prior stroke] [p-interaction = 0.02]) or who were younger (HR 2.42 [<65 years old] vs HR 1.49 [>/=65 years old] [p-interaction = 0.04]). INTERPRETATION: Delirium after cardiac surgery is a strong independent predictor of mortality up to 10 years postoperatively, especially in younger individuals and in those without prior stroke. Future studies are needed to determine the impact of delirium prevention and/or treatment in long-term patient mortality.

Do management strategies for coronary artery disease influence 6-year cognitive outcomes?

BACKGROUND: Previous uncontrolled studies have suggested that there is late cognitive decline after coronary artery bypass grafting that may be attributable to use of the cardiopulmonary bypass pump. METHODS: In this prospective, nonrandomized, longitudinal study, we compared cognitive outcomes after on-pump coronary artery bypass surgery (n = 152) with off-pump bypass surgery patients (n = 75); nonsurgical cardiac comparison subjects (n = 99); and 69 heart-healthy comparison (HHC) subjects. The primary outcome measure was change from baseline to 72 months in the following cognitive domains: verbal memory, visual memory, visuoconstruction, language, motor speed, psychomotor speed, attention, executive function, and a composite global score. RESULTS: There were no consistent differences in 72-month cognitive outcomes among the three groups with coronary artery disease (CAD). The CAD groups had lower baseline performance, and a greater degree of decline compared with HHC. The degree of change was small, with none of the groups having more than 0.5 SD decline. None of the groups was substantially worse at 72 months compared with baseline. CONCLUSIONS: Compared with subjects with no vascular disease risk factors, the CAD patients had lower baseline cognitive performance and greater degrees of decline over 72 months, suggesting that in these patients, vascular disease may have an impact on cognitive performance. We found no significant differences in the long-term cognitive outcomes among patients with various CAD therapies, indicating that management strategy for CAD is not an important determinant of long-term cognitive outcomes.

Subjective memory symptoms in surgical and nonsurgical coronary artery patients: 6-year follow-up.

BACKGROUND: Self-reported cognitive and memory complaints after coronary artery bypass graft (CABG) operations are common. Several studies have attempted to quantify the incidence of such complaints and to examine the relationship between subjective and objective cognitive functioning, but the etiology and longitudinal course of these self-reports remain unclear. METHODS: Measures of subjective memory complaints were compared in two groups: 220 CABG patients and 92 nonsurgical cardiac patients at 3 months, and 1, 3, and 6 years. At 6 years, additional measures were used to quantify memory self-assessment. The frequency of subjective complaints at each time point was determined, and associations with objective cognitive performance as well as depression were examined. RESULTS: At early (3-month or 1-year) follow-up, subjective memory complaints were reported more often by the CABG than the nonsurgical group (45.5% vs 17.0%, p < 0.0001). By 6 years, the frequency of complaints was similar (52%) in both groups. Subjective memory ratings were significantly correlated with performance on several memory tests at 6 years. This relationship was not confounded by depression. CONCLUSIONS: Subjective memory complaints are more frequent early in follow-up in patients undergoing CABG than in controls, but are similar by 6 years. The increase in subjective complaints over time may be related to progression of underlying cerebrovascular disease. Unlike previous studies, we found that subjective memory assessments were correlated with objective performance on several memory tests. Although subjective memory complaints are more common in patients with depression, they cannot be explained by depression alone.

Cognition 6 years after surgical or medical therapy for coronary artery disease.

OBJECTIVE: The choice of coronary artery bypass grafting (CABG) as an intervention for coronary artery disease has been clouded by concerns about postoperative cognitive decline. Long-term cognitive decline after CABG has been reported, but without appropriate control subjects, it is not known whether this decline is specific to CABG or related to other factors such as cerebrovascular disease. METHODS: This prospective, observational study of patients with diagnosed coronary artery disease included 152 CABG and 92 nonsurgical cardiac comparison patients from one institution. The main outcome measure was within-patient change in cognitive performance for eight cognitive domains from baseline to 12- and 72-month follow-up. RESULTS: Mild late cognitive decline was observed for both study groups, but despite greater than 80% power to detect a 0.2 standard deviation difference, there were no statistically significant differences between the surgical and nonsurgical patients in the degree of change from 12 to 72 months for any cognitive domain. There was also no difference between groups in the degree of change from baseline to 72 months or in the number of patients with a Mini-Mental State Examination score in the clinically impaired range at 72 months. INTERPRETATION: Late cognitive decline does occur in patients who have undergone CABG surgery, but the degree of this decline does not differ from that observed in patients of similar age with coronary artery disease who have not undergone CABG. Therefore, late cognitive decline after CABG is not specific to the use of cardiopulmonary bypass.

Neurocognitive outcomes 3 years after coronary artery bypass graft surgery: a controlled study.

BACKGROUND: Cardiopulmonary bypass has been implicated in the late cognitive decline that has been reported after coronary artery bypass graft (CABG) surgery. Because most studies did not include a control group, a causal link of such decline with the use of cardiopulmonary bypass has not been established. METHODS: We compared changes in cognitive performance from baseline to 3 years in patients undergoing on-pump CABG (n = 152) with those of three control groups: patients with off-pump surgery (n = 75); with diagnosed coronary artery disease but no surgery (n = 99); and without coronary artery disease risk factors (n = 69). Neuropsychological performance was assessed by standardized tests of attention, language, verbal and visual memory, visuospatial, executive function, and psychomotor and motor speed. RESULTS: Relative to their baseline performance, no group had significantly lower performance at 36 months for any of the cognitive domains. From 12 to 36 months, there were no statistically significant differences in the degree of change between the on- and off-pump surgery groups. There was a trend toward mild decline in some cognitive domains, but overall differences among groups in degree of change over time were not statistically significant. CONCLUSIONS: We found a mild but nonsignificant trend toward late postoperative cognitive decline for all study groups with coronary artery disease, but no significant differences in the degree of late postoperative cognitive decline after on-pump compared with off-pump surgery. These findings suggest that previously reported late decline after bypass surgery is not specific to use of cardiopulmonary bypass.

Early postoperative cognitive dysfunction and blood pressure during coronary artery bypass graft operation.

OBJECTIVE: To determine the relationship between change in blood pressure during coronary artery bypass graft operations and early cognitive dysfunction. DESIGN: Cohort study. SETTING: Quaternary care facility. Patients Fifteen patients undergoing coronary artery bypass graft operations who were at high risk for postoperative stroke. Preoperative and intraoperative mean arterial pressures (MAPs) were measured in all patients. Intervention A subset of patients underwent preoperative and postoperative magnetic resonance imaging. Main Outcome Measure Change in cognitive performance, using the Mini-Mental State Examination and other simple cognitive tests. RESULTS: A drop in MAP (preoperatively to intraoperatively) predicted a decrease in Mini-Mental State Examination score. When change in MAP was dichotomized (after excluding an outlier), subjects with a small decrease improved on the Mini-Mental State Examination by 1 point, whereas those with a large drop in MAP worsened by 1.4 points (P = .04). CONCLUSION: A drop in MAP from a preoperative baseline may put patients at risk for early cognitive dysfunction after a coronary artery bypass graft operation.

Watershed strokes after cardiac surgery: diagnosis, etiology, and outcome.

BACKGROUND AND PURPOSE: Watershed strokes are more prevalent after cardiac surgery than in other stroke populations, but their mechanism in this setting is not understood. We investigated the role of intraoperative blood pressure in the development of watershed strokes and used MRI to evaluate diagnosis and outcomes associated with this stroke subtype. METHODS: From 1998 to 2003 we studied 98 patients with clinical stroke after cardiac surgery who underwent MRI with diffusion-weighted imaging. We used logistic regression to explore the relationship between mean arterial pressure and watershed infarcts, between watershed infarcts and outcome, and chi(2) analyses to compare detection by MRI versus CT of watershed infarcts. RESULTS: Bilateral watershed infarcts were present on 48% of MRIs and 22% of CTs (P<0.0001). Perioperative stroke patients with bilateral watershed infarcts, compared with those with other infarct patterns, were 17.3 times more likely to die, 12.5 and 6.2 times more likely to be discharged to a skilled nursing facility and to acute rehabilitation, respectively, than to be discharged home (P=0.0004). Patients with a decrease in mean arterial pressure of at least 10 mm Hg (intraoperative compared with preoperative) were 4.1 times more likely to have bilateral watershed infarcts than other infarct patterns. CONCLUSIONS: Bilateral watershed infarcts after cardiac surgery are most reliably detected by diffusion-weighted imaging MRI and are associated with poor short-term outcome, compared with other infarct types. The mechanism may include an intraoperative drop in blood pressure from a patient's baseline. These findings have implications for future clinical practice and research.

Cognitive and neurobehavioral dysfunction after cardiac bypass procedures.

From a cognitive standpoint, CABG as currently practiced appears to be safe for the great majority of patients, but transient changes involving memory, executive functions, and motor speed may still occur in a subset of patients during the first few days to weeks after CABG. The etiology most likely is multifactorial and includes a synergistic effect of microemboli, hypo-perfusion, and other variables associated with major surgery. Older age and degree of pre-existing cerebrovascular disease have been identified as important risk factors. The short-term cognitive changes appear to be reversible by 3 months after surgery for most patients. Late cognitive decline after CABG,occurring between 1 and 5 years after the surgery, has been well documented,but controlled studies demonstrating that this decline is specifically attributable to the use of cardiopulmonary bypass itself rather than to progression of underlying cerebrovascular disease or other age-related changes are pending.

Stroke and encephalopathy after cardiac surgery: an update.

BACKGROUND AND PURPOSE: As a result of advances in surgical, anesthetic, and medical management, cardiac surgery can now be performed on older, sicker patients, some of whom have had prior cardiac interventions. As surgical mortality has declined in recent years, attention has focused on the complications of stroke and encephalopathy after cardiac surgery. SUMMARY OF REVIEW: Patients with preexisting cerebrovascular disease are at increased risk for these untoward neurological outcomes, which are associated with longer lengths of hospital stay, higher costs, and greater mortality. The mechanisms underlying these neurological events may include microemboli and hypoperfusion during surgery, and postoperative atrial fibrillation. Predictive models, based on information available before surgery, allow identification of these "high risk" patients. CONCLUSIONS: Establishing the degree of functionally significant vascular disease of the brain before surgery should be an essential part of the preoperative evaluation, particularly when modifications in surgical technique or novel neuroprotective agents are being evaluated.

Quantitative methods for tracking cognitive change 3 years after coronary artery bypass surgery.

The analysis and interpretation of change in cognitive function test scores after coronary artery bypass grafting (CABG) present considerable statistical challenges. Application of hierarchical linear statistical models can estimate the effects of a surgical intervention on the time course of multiple biomarkers. We use an "analyze then summarize" approach whereby we estimate the intervention effects separately for each cognitive test and then pool them, taking appropriate account of their statistical correlations. The model accounts for dropouts at follow-up, the chance of which may be related to past cognitive score, by implicitly imputing the missing data from individuals' past scores and group patterns. We apply this approach to a study of the effects of CABG on the time course of cognitive function as measured by 16 separate neuropsychological test scores, clustered into 8 cognitive domains. The study includes measurements on 140 CABG patients and 92 nonsurgical controls at baseline, and at 3, 12, and 36 months. Our "analyze then summarize" method allows us to identify differences between the treatment groups in individual tests as well as in aggregate measures. It takes into account the correlation structure of the data and thereby produces more precise results than summarizing before analyzing. The methods used have application to a wide range of intervention studies in which multiple biomarkers are followed over time to quantify health effects. Software to implement the methods in the R statistical package is available from the authors at http://www.biostat.jhsph.edu/sbarry/software/ATSrcode.pdf.