Easily Screenable Characteristics Associated with Cognitive Improvement and Dysfunction After Carotid Endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) is an effective treatment for the prevention of stroke in patients with carotid artery stenosis. We aimed to clarify the incidence and risk factors for early cognitive dysfunction (eCD) and early cognitive improvement (eCI), defined as change in cognitive performance ≤24 hours after surgery, using a battery of neuropsychometric tests. METHODS: In total, 585 patients undergoing CEA were tested with neuropsychometric tests before and after surgery; 155 patients undergoing "simple" spine surgery were the reference group. Patient performance for each test was evaluated by z scores. Cognitive change was defined as eCD (or eCI) if: 1) patients had a z score ≤-2 (or ≥2) in ≥2 cognitive domains or 2) patients had mean z scores across all domains ≤-1.5 (or ≥1.5). Associations between the categorical cognitive outcomes and variables of interest were modeled using the proportional odds model. RESULTS: Of the 585 subjects, 24% had eCD, 6% had eCI, and 70% had "no change." Patients who had eCD were more likely to be statin naïve (odds ratio [OR] 1.23 [1.03-1.48], P = 0.02) or women (OR 1.27 [1.06-1.53], P = 0.02). Those with eCI were less likely to have less formal education (OR 0.95 [0.90-1.00], P = 0.04) and less likely to have diabetes mellitus (OR 0.8 [0.65-0.99], P = 0.04). CONCLUSIONS: Patients having CEA may develop eCD or eCI postoperatively. Medications likely to be associated with less eCD are statins and aspirin, which correlate most strongly in asymptomatic patients. In addition to confirming previous findings, we found that women were more likely than men to develop eCD. More sex-specific studies and analysis are needed to better explore these findings.

An imbalance between specialized pro-resolving lipid mediators and pro-inflammatory leukotrienes promotes instability of atherosclerotic plaques.

Chronic unresolved inflammation plays a causal role in the development of advanced atherosclerosis, but the mechanisms that prevent resolution in atherosclerosis remain unclear. Here, we use targeted mass spectrometry to identify specialized pro-resolving lipid mediators (SPM) in histologically-defined stable and vulnerable regions of human carotid atherosclerotic plaques. The levels of SPMs, particularly resolvin D1 (RvD1), and the ratio of SPMs to pro-inflammatory leukotriene B4 (LTB4), are significantly decreased in the vulnerable regions. SPMs are also decreased in advanced plaques of fat-fed Ldlr-/- mice. Administration of RvD1 to these mice during plaque progression restores the RvD1:LTB4 ratio to that of less advanced lesions and promotes plaque stability, including decreased lesional oxidative stress and necrosis, improved lesional efferocytosis, and thicker fibrous caps. These findings provide molecular support for the concept that defective inflammation resolution contributes to the formation of clinically dangerous plaques and offer a mechanistic rationale for SPM therapy to promote plaque stability.

Attending Handoff Is Correlated with the Decision to Delay Extubation After Surgery.

BACKGROUND: Factors including ASA physical status, blood loss, and case length have been described as correlating with the decision to delay tracheal extubation after specific surgical procedures. In this retrospective study, we investigated whether handoffs by anesthesia attendings were associated with delayed extubation after general anesthesia for a broad range of surgical procedures. METHODS: We reviewed the records of 37,824 patients who underwent general anesthesia with an endotracheal tube for surgery (excluding tracheostomy surgery, cardiac surgeries, and liver and lung transplant surgeries) from 2008 to 2013 at Columbia University Medical Center. Our primary outcome was whether the patient was extubated at the end of the surgical case. We hypothesized that attending handoff was a factor that would independently affect the decision of the anesthesiologist to extubate at the end of the surgical case. In addition, we investigated whether the association between handoff and extubation was affected by the timing of the procedure (ending in the daytime versus evening hours) by including an interaction term in the analysis. We adjusted for other variables affecting the decision to delay extubation. RESULTS: Patients (5.4%, n = 2033) were not extubated in the operating room after the completion of their surgery. Cases with an attending handoff appeared to have a greater risk of delayed extubation with an adjusted risk ratio (aRR) of 1.14 (95% confidence interval [CI], 1.03-1.25). Further analysis demonstrated that the attending handoff had a significant effect in daytime cases (aRR, 1.62; 95% CI, 1.29-2.04) but not in evening cases (aRR, 1.07; 95% CI, 0.97-1.19). CONCLUSIONS: Attending handoff was an independent significant factor that increased the risk for the delay of extubation at the end of a surgical case.

Impact of Cognitive Dysfunction on Survival in Patients With and Without Statin Use Following Carotid Endarterectomy.

BACKGROUND: Early cognitive dysfunction (eCD) is a subtle form of neurological injury observed in ∼25% of carotid endarterectomy (CEA) patients. Statin use is associated with a lower incidence of eCD in asymptomatic patients having CEA. OBJECTIVE: To determine whether eCD status is associated with worse long-term survival in patients taking and not taking statins. METHODS: This is a post hoc analysis of a prospective observational study of 585 CEA patients. Patients were evaluated with a battery of neuropsychometric tests before and after surgery. Survival was compared for patients with and without eCD stratifying by statin use. At enrollment, 366 patients were on statins and 219 were not. Survival was assessed by using Kaplan-Meier methods and multivariable Cox proportional hazards models. RESULTS: Age ≥75 years (P = .003), diabetes mellitus (P < .001), cardiac disease (P = .02), and statin use (P = .014) are significantly associated with survival univariately (P < .05) by use of the log-rank test. By Cox proportional hazards model, eCD status and survival adjusting for univariate factors within statin and nonstatin use groups suggested a significant effect by association of eCD on survival within patients not taking statin (hazard ratio, 1.61; 95% confidence interval, 1.09-2.40; P = .018), and no significant effect of eCD on survival within patients taking statin (hazard ratio, 0.98; 95% confidence interval, 0.59-1.66; P = .95). CONCLUSION: eCD is associated with shorter survival in patients not taking statins. This finding validates eCD as an important neurological outcome and suggests that eCD is a surrogate measure for overall health, comorbidity, and vulnerability to neurological insult. ABBREVIATIONS: aHR, adjusted hazards ratiosCEA, carotid endarterectomyCI, confidence intervalDM, diabetes mellituseCD, early cognitive dysfunctionNDI, National Death IndexNLR, neutrophil/lymphocyte ratioSD, standard deviationSEM, standard error of the mean.

Deficits of hand coordination and laterality of carotid endarterectomy.

OBJECT: Neurocognitive performance is used to assess multiple cognitive domains, including motor coordination, before and after carotid endarterectomy (CEA). Although gross motor strength is impaired with ischemia of large cortical areas or of the internal capsule, the authors hypothesize that patients undergoing CEA demonstrate significant motor deficits of hand coordination contralateral to the operative side, which is more clearly manifest in the nondominant hand than in the dominant hand with ischemia of smaller cortical areas. METHODS: The neurocognitive performance of 374 patients was evaluated with a battery of neuropsychometric tests. Both asymptomatic and symptomatic patients undergoing CEA were included. The authors evaluated the patients' dominant and nondominant hand performance on the Grooved Pegboard test, a test of hand coordination, to demonstrate their functional laterality. Neurocognitive dysfunction was evaluated as the difference in performance before and after CEA according to group-rate and event-rate analyses. The z scores were generated for all tests using a reference group of patients who were having simple spine surgery. Dominant and nondominant motor coordination functions were evaluated as raw scores and as calculated z scores. RESULTS: According to event-rate analysis, significantly more patients undergoing CEA of the opposite carotid artery demonstrated nondominant than dominant hand deficits of coordination (41.2% vs 26.4%, respectively, p = 0.02). Similarly, according to group-rate analysis, in patients undergoing CEA of the opposite carotid artery, raw difference scores from the Grooved Pegboard test reflected greater nondominant than dominant hand deficits of coordination (21.0 ± 54.4 vs 9.7 ± 37.0, respectively, p = 0.02). CONCLUSIONS: Patients undergoing CEA of the opposite carotid artery are more likely to demonstrate nondominant than dominant hand deficits of coordination because of greater dexterity in the dominant hand before surgery.

Republished: Society for Neuroscience in Anesthesiology and Critical Care expert consensus statement: Anesthetic management of endovascular treatment for acute ischemic stroke.

Literature on the anesthetic management of endovascular treatment of acute ischemic stroke (AIS) is limited. Anesthetic management during these procedures is still mostly dependent on individual or institutional preferences. Thus, the Society of Neuroscience in Anesthesiology and Critical Care (SNACC) created a task force to provide expert consensus recommendations on anesthetic management of endovascular treatment of AIS. The task force conducted a systematic literature review (up to August 2012). Because of the limited number of research articles relating to this subject, the task force solicited opinions from experts in this area. The task force created a draft consensus statement based on the available data. Classes of recommendations and levels of evidence were assigned to articles specifically addressing anesthetic management during endovascular treatment of stroke using the standard American Heart Association evidence rating scheme. The draft consensus statement was reviewed by the Task Force, SNACC Executive Committee and representatives of Society of NeuroInterventional Surgery (SNIS) and Neurocritical Care Society (NCS) reaching consensus on the final document. For this consensus statement the anesthetic management of endovascular treatment of AIS was subdivided into 12 topics. Each topic includes a summary of available data followed by recommendations. This consensus statement is intended for use by individuals involved in the care of patients with acute ischemic stroke, such as anesthesiologists, interventional neuroradiologists, neurologists, neurointensivists and neurosurgeons.

Radiographic absence of the posterior communicating arteries and the prediction of cognitive dysfunction after carotid endarterectomy.

OBJECT: Approximately 25% of patients exhibit cognitive dysfunction 24 hours after carotid endarterectomy (CEA). One of the purported mechanisms of early cognitive dysfunction (eCD) is hypoperfusion due to inadequate collateral circulation during cross-clamping of the carotid artery. The authors assessed whether poor collateral circulation within the circle of Willis, as determined by preoperative CT angiography (CTA) or MR angiography (MRA), could predict eCD. METHODS: Patients who underwent CEA after preoperative MRA or CTA imaging and full neuropsychometric evaluation were included in this study (n = 42); 4 patients were excluded due to intraoperative electroencephalographic changes and subsequent shunt placement. Thirty-eight patients were included in the statistical analyses. Patients were stratified according to posterior communicating artery (PCoA) status (radiographic visualization of at least 1 PCoA vs of no PCoAs). Variables with p < 0.20 in univariate analyses were included in a stepwise multivariate logistic regression model to identify predictors of eCD after CEA. RESULTS: Overall, 23.7% of patients exhibited eCD. In the final multivariate logistic regression model, radiographic absence of both PCoAs was the only independent predictor of eCD (OR 9.64, 95% CI 1.43-64.92, p = 0.02). CONCLUSIONS: The absence of both PCoAs on preoperative radiographic imaging is predictive of eCD after CEA. This finding supports the evidence for an underlying ischemic etiology of eCD. Larger studies are justified to verify the findings of this study. Clinical trial registration no.: NCT00597883 ( http://www.clinicaltrials.gov ).

Effect of atropine dose on heart rate during electroconvulsive therapy.

INTRODUCTION: Transient bradycardia during the stimulation phase of electroconvulsive therapy (ECT) is a well-known clinical observation. The optimal dose of atropine needed to prevent bradycardia has not been determined. This study was designed to investigate the effect of low doses of atropine on heart rate during ECT. METHODS: Patients who received at least 2 different doses of atropine over their series of right unilateral ECT were included in the analysis. The anesthetic consisted of 0, 0.2, 0.3, or 0.4 mg of atropine, methohexital, and succinylcholine. Heart rate was measured by the RR interval, the time between sequential R waves on the electrocardiogram. Analysis was performed using logistic multivariate regression and repeated-measures multivariate analysis of variance. RESULTS: One hundred eighteen ECT sessions were identified from 19 patients. Patients were grouped into 4 groups by atropine dose (0, 0.2, 0.3, or 0.4 mg) with 9, 33, 13, and 63 ECT sessions identified for each dose, respectively. Patients who received atropine had significantly less bradycardia after electrical stimulus and a faster heart rate through the seizure than patients who did not receive atropine. There was no significant difference in heart rate between patients receiving 0.2, 0.3, and 0.4 mg of atropine at any time point. There was no significant difference in heart rate at time points after the seizure conclusion in any group of patients. CONCLUSION: Low-dose atropine results in significantly less bradycardia after electrical stimulus. There was no significant difference in heart rate across low doses of atropine.

Society for Neuroscience in Anesthesiology and Critical Care Expert consensus statement: anesthetic management of endovascular treatment for acute ischemic stroke*: endorsed by the Society of NeuroInterventional Surgery and the Neurocritical Care Society.

Literature on the anesthetic management of endovascular treatment of acute ischemic stroke (AIS) is limited. Anesthetic management during these procedures is still mostly dependent on individual or institutional preferences. Thus, the Society of Neuroscience in Anesthesiology and Critical Care (SNACC) created a task force to provide expert consensus recommendations on anesthetic management of endovascular treatment of AIS. The task force conducted a systematic literature review (up to August 2012). Because of the limited number of research articles relating to this subject, the task force solicited opinions from experts in this area. The task force created a draft consensus statement based on the available data. Classes of recommendations and levels of evidence were assigned to articles specifically addressing anesthetic management during endovascular treatment of stroke using the standard American Heart Association evidence rating scheme. The draft consensus statement was reviewed by the Task Force, SNACC Executive Committee and representatives of Society of NeuroInterventional Surgery (SNIS) and Neurocritical Care Society (NCS) reaching consensus on the final document. For this consensus statement the anesthetic management of endovascular treatment of AIS was subdivided into 12 topics. Each topic includes a summary of available data followed by recommendations. This consensus statement is intended for use by individuals involved in the care of patients with acute ischemic stroke, such as anesthesiologists, interventional neuroradiologists, neurologists, neurointensivists, and neurosurgeons.

Neutrophil-lymphocyte ratio as a predictor of cognitive dysfunction in carotid endarterectomy patients.

BACKGROUND: Systemic inflammation has been implicated in the development of cognitive dysfunction following carotid endarterectomy (CEA). Neutrophil-lymphocyte ratio (NLR) is a reliable measure of systemic inflammation. We hypothesize that patients with elevated preoperative NLR have increased risk of cognitive dysfunction 1 day after CEA. METHODS: Five hundred fifty-one patients scheduled for CEA were enrolled at Columbia University in New York, NY from 1995 to 2012. NLR was retrospectively reviewed; only 432 patients had preoperative NLR values available within 2 weeks of CEA. NLR was analyzed as a continuous variable and categorically with a cutoff of ≥5 and <5 and equal tertiles, as done in previous studies. RESULTS: Patients with cognitive dysfunction had significantly higher NLR than those without cognitive dysfunction (4.5 ± 4.0 vs 3.2 ± 2.6; P < .001). The incidence of cognitive dysfunction was significantly higher in patients with NLR ≥5 than NLR <5 (34.7% vs 12.8%; P < .001). Significantly fewer patients in the low tertile had cognitive dysfunction than in the high tertile (6.9% vs 25.9%; P <.001) and middle tertile (6.9% vs 17.4%; P = .006). In the final multivariate model, diabetes mellitus (odds ratio [OR], 2.03; 95% confidence interval [CI], 1.08-3.75; P = .03) and NLR ≥5 (OR, 3.38; 95% CI, 1.81-6.27; P < .001) were significantly associated with higher odds of cognitive dysfunction, while statin use was significantly associated with lower odds (OR, 0.48; 95% CI, 0.27-0.84; P = .01). CONCLUSIONS: Preoperative NLR is associated with cognitive dysfunction 1 day after CEA. NLR ≥5 and diabetes mellitus are significantly associated with increased odds of cognitive dysfunction whereas statin use is significantly associated with decreased odds.

Arterial blood pressure management during carotid endarterectomy and early cognitive dysfunction.

BACKGROUND: A common practice during cross-clamp of carotid endarterectomy (CEA) is to manage mean arterial pressure (MAP) above baseline to optimize the collateral cerebral blood flow and reduce the risk of ischemic stroke. OBJECTIVE: To determine whether MAP management ≥20% above baseline during cross-clamp is associated with lower risk of early cognitive dysfunction, a subtler form of neurological injury than stroke. METHODS: One hundred eighty-three patients undergoing CEA were enrolled in this ad hoc study. All patients had radial arterial catheters placed before the induction of general anesthesia. MAP was managed at the discretion of the anesthesiologist. All patients were evaluated with a battery of neuropsychometric tests preoperatively and 24 hours postoperatively. RESULTS: Overall, 28.4% of CEA patients exhibited early cognitive dysfunction (eCD). Significantly fewer patients with MAP ≥20% above baseline during cross-clamp exhibited eCD than those managed <20% above (11.6% vs 38.6%, P < .001). In a multivariate logistic regression model, MAP ≥20% above baseline during the cross-clamp period was associated with significantly lower risk of eCD (odds ratio [OR], 0.18 [0.07-0.40], P < .001), whereas diabetes mellitus (OR, 2.73 [1.14-6.61], P = .03) and each additional year of education (OR, 1.19 [1.06-1.34], P = .003) were associated with significantly higher risk of eCD. CONCLUSION: The observations of this study suggest that MAP management ≥20% above baseline during cross-clamp of the carotid artery may be associated with lower risk of eCD after CEA. More prospective work is necessary to determine whether MAP ≥20% above baseline during cross-clamp can improve the safety of this commonly performed procedure.

Reduced middle cerebral artery velocity during cross-clamp predicts cognitive dysfunction after carotid endarterectomy.

Transcranial Doppler (TCD) is a useful monitor that can be utilized during carotid endarterectomy (CEA). Cognitive dysfunction is a subtler and more common form of neurologic injury than stroke. We aimed to determine whether reduced middle cerebral artery (MCA) mean velocity (MV) predicts cognitive dysfunction and if so, whether a threshold of increased risk of cognitive dysfunction can be identified. One hundred twenty-four CEA patients were included in this observational study and neuropsychometrically evaluated preoperatively and 24 hours postoperatively. MCA-MV was measured by TCD and percentage of baseline during cross-clamp was calculated (MV(cross-clamp)/MV(baseline)). Patients with cognitive dysfunction had significantly lower MV during cross-clamp than those without cognitive dysfunction (33.1 ± 13.7 cm/s versus 39.6 ± 16.0 cm/s, p=0.02). In the final multivariate model, each percent reduction in MV was significantly associated with greater risk of cognitive dysfunction (odds ratio [OR]: 0.05 [95% confidence interval {CI} 0.01-0.23], p < 0.001) while statin use was associated with lower risk (OR: 0.33 [95% CI 0.12-0.92], p = 0.03). Using receiver operator characteristic curve analysis, the Youden index identified 72% of baseline MV during cross-clamp as the cutoff of maximum discrimination. Significantly more patients with MV < 72% of baseline during cross-clamp exhibited cognitive dysfunction than patients with MV ≥ 72% of baseline (74.1% versus 27.1%, p < 0.001). Reduced MCA-MV during cross-clamp is a predictor of cognitive dysfunction exhibited 24 hours after CEA. MCA-MV reduced to <72% of baseline, or a ≥28% reduction from baseline, is the threshold most strongly associated with increased risk of cognitive dysfunction. These observations should be considered by all clinicians that utilize intraoperative monitoring for CEA.

Middle cerebral artery pulsatility index and cognitive improvement after carotid endarterectomy for symptomatic stenosis.

OBJECT: Transcranial Doppler (TCD) is frequently used to evaluate peripheral cerebral resistance and cerebral blood flow (CBF) in the middle cerebral artery prior to and during carotid endarterectomy (CEA). Patients with symptomatic carotid artery stenosis may have reduced peripheral cerebral resistance to compensate for inadequate CBF. The authors aim to determine whether symptomatic patients with reduced peripheral cerebral resistance prior to CEA demonstrate increased CBF and cognitive improvement as early as 1 day after CEA. METHODS: Fifty-three patients with symptomatic CEA were included in this observational study. All patients underwent neuropsychometric evaluation 24 hours or less preoperatively and 1 day postoperatively. The MCA was evaluated using TCD for CBF mean velocity (MV) and pulsatility index (PI). Pulsatility index ≤ 0.80 was used as a cutoff for reduced peripheral cerebral resistance. RESULTS: Significantly more patients with baseline PI ≤ 0.80 exhibited cognitive improvement 1 day after CEA than those with PI > 0.80 (35.0% vs 6.1%, p = 0.007). Patients with cognitive improvement had a significantly greater increase in CBF MV than patients without cognitive improvement (13.4 ± 17.1 cm/sec vs 4.3 ± 9.9 cm/sec, p = 0.03). In multivariate regression model, a baseline PI ≤ 0.80 was significantly associated with increased odds of cognitive improvement (OR 7.32 [1.40-59.49], p = 0.02). CONCLUSIONS: Symptomatic CEA patients with reduced peripheral cerebral resistance, measured as PI ≤ 0.80, are likely to have increased CBF and improved cognitive performance as early as 1 day after CEA for symptomatic carotid artery stenosis. Revascularization in this cohort may afford benefits beyond prevention of future stroke. Clinical trial registration no: NCT00597883 ( ClinicalTrials.gov ).

Apolipoprotein E-ε4 polymorphism and cognitive dysfunction after carotid endarterectomy.

Approximately 25% of patients undergoing carotid endarterectomy (CEA) exhibit cognitive dysfunction (CD) 1 day and 1 month after CEA. The apolipoprotein E (apoE)-ε4 polymorphism has been previously identified as a robust independent risk factor for CD 1 month after CEA. We aimed to determine whether the apoE-ε4 polymorphism is also an independent risk factor for CD as early as 1 day after CEA and to confirm the previous findings at 1 month. Patients undergoing elective CEA (n=411) were enrolled with written informed consent in this follow-up observational study. CD was evaluated via an extensive neuropsychometric battery. apoE-ε4 carriers exhibited significantly more CD 1 day (30.1% versus 17.9%, p=0.01) and 1 month (25.7% versus 9.8%, p=0.001) after CEA compared to non-carriers. Multivariate regression models were generated to determine independent predictors of CD. At 1 day, apoE-ε4 was significantly associated with higher risk of CD (odds ratio [OR]: 2.24 [95% confidence interval 1.29-3.84], p=0.004), while statin use was significantly associated with lower risk (OR: 0.40 [0.24-0.67], p<0.001). At 1 month, apoE-ε4 was significantly associated with higher risk of CD (OR: 3.14 [1.53-6.38], p=0.002), while symptomatic status was significantly associated with lower risk (OR: 0.45 [0.20-0.94], p=0.03). The apoE-ε4 polymorphism is an independent risk factor for CD as early as 1 day after CEA and is confirmed to be an independent risk factor for CD at 1 month as well.

Factors that correlate with the decision to delay extubation after multilevel prone spine surgery.

BACKGROUND: Multilevel spinal decompressions and fusions often require long anesthetic and operative times, which may result in airway edema and prolonged postoperative intubation. Delayed extubation can lead to bronchopulmonary infections and other complications. This study analyzed which factors correlated with the decision to delay extubation after multilevel spine surgery. METHODS: We reviewed the records of 289 patients who underwent multilevel spine surgery lasting ≥8 hours in the prone position from 2006 to 2012. Variables hypothesized to affect the decision of the anesthesiologist to delay extubation at the end of the surgery were collected. These included preoperative factors (age, sex, ASA class, history of obstructive sleep apnea, BMI, previous spine surgery, current cervical surgery, anterior in addition to posterior spine surgery, emergency surgery) and intraoperative factors (difficult intubation, number of surgical levels, case time, estimated blood loss, fluid and blood administration, attending handoff and resident handoff, and case end time). We also compared the incidence of pulmonary postoperative complications between patients extubated at the end of the case to patients who had a delayed extubation. RESULTS: A total of 126 patients (44%) were kept intubated after multilevel spine surgery. Multiple linear regression analysis showed factors that correlated with prolonged intubation which included age, ASA class, procedure duration, extent of surgery, total crystalloid volume administered, total blood volume administered, and the case end time. Patients who had a delayed extubation had a 3-fold higher rate of postoperative pneumonia. CONCLUSIONS: Our study found that age, ASA class, procedure duration, extent of surgery, and total crystalloid and blood volume administered correlate with the decision to delay extubation in multilevel prone spine surgery. It also finds that the time the case ends is an independent variable that correlates with the decision not to extubate at the end of a long multilevel spinal surgery. The incidence of postoperative pneumonia is higher in patients who had a delayed extubation after surgery.

Phosphodiesterase 4D single-nucleotide polymorphism 83 and cognitive dysfunction in carotid endarterectomy patients.

BACKGROUND: Phosphodiesterase 4D (PDE4D), through the regulation of cyclic AMP, modulates inflammation and other processes that affect atherosclerosis and stroke. A PDE4D polymorphism, single-nucleotide polymorphism (SNP) 83 (rs966221), is associated with ischemic stroke. The association of SNP 83 with postoperative cognitive dysfunction has never been investigated. OBJECTIVE: To determine whether SNP 83 is associated with cognitive dysfunction 1 day and 1 month following carotid endarterectomy (CEA). METHODS: Three hundred fourteen patients with high-grade carotid stenosis scheduled for CEA consented to participate in this single-center cohort study of cognitive dysfunction. RESULTS: Patients with the C/C genotype of SNP 83 exhibited significantly more cognitive dysfunction at 1 day (29.7%) than the C/T (15.8%, P = .008) and T/T (12.7%, P = .01) genotypes. In a multivariate logistic regression model, C/T and T/T genotypes were both associated with significantly decreased odds of cognitive dysfunction compared with the C/C genotype (odds ratio, 0.45 [0.24-0.83], P = .01 and odds ratio, 0.33 [0.12-0.77], P = .02). There were no significant associations at 1 month. CONCLUSION: The C/C genotype of SNP 83 is significantly associated with the highest incidence of cognitive dysfunction 1 day following CEA in comparison with the C/T and T/T genotypes. This PDE4D genotype may lead to accelerated cyclic AMP degradation and subsequently elevated inflammation 1 day after CEA. These observations, in conjunction with previous studies, suggest that elevated inflammatory states may be partially responsible for the development of cognitive dysfunction after CEA, but more investigation is required.

Inflammation and cognitive dysfunction in type 2 diabetic carotid endarterectomy patients.

OBJECTIVE: Type 2 diabetic patients have a high incidence of cerebrovascular disease, elevated inflammation, and high risk of developing cognitive dysfunction following carotid endarterectomy (CEA). To elucidate the relationship between inflammation and the risk of cognitive dysfunction in type 2 diabetic patients, we aim to determine whether elevated levels of systemic inflammatory markers are associated with cognitive dysfunction 1 day after CEA. RESEARCH DESIGN AND METHODS: One hundred fifteen type 2 diabetic CEA patients and 156 reference surgical patients were recruited with written informed consent in this single-center cohort study. All patients were evaluated with an extensive battery of neuropsychometric tests. Preoperative monocyte counts, HbA1c, C-reactive protein (CRP), intercellular adhesion molecule 1, and matrix metalloproteinase 9 activity levels were obtained. RESULTS: In a multivariate logistic regression model constructed to identify predictors of cognitive dysfunction in type 2 diabetic CEA patients, each unit of monocyte counts (odds ratio [OR] 1.76 [95% CI 1.17-2.93]; P=0.005) and CRP (OR 1.17 [1.10-1.29]; P<0.001) was significantly associated with higher odds of developing cognitive dysfunction 1 day after CEA in type 2 diabetic patients. CONCLUSIONS: Type 2 diabetic patients with elevated levels of preoperative systemic inflammatory markers exhibit more cognitive dysfunction 1 day after CEA. These observations have implications for the preoperative medical management of this high-risk group of surgical patients undergoing carotid revascularization with CEA.

Complement polymorphisms and cognitive dysfunction after carotid endarterectomy.

OBJECT: The role of genetic polymorphisms in the neurological outcome of patients after carotid endarterectomy (CEA) remains unclear. There are single nucleotide polymorphisms (SNPs) that predispose patients to postoperative cognitive dysfunction (CD). We aim to assess the predictability of three complement cascade-related SNPs for CD in patients having CEAs. METHODS: In 252 patients undergoing CEA, genotyping was performed for the following polymorphisms: complement component 5 (C5) rs17611, mannose-binding lectin 2 (MBL2) rs7096206, and complement factor H (CFH) rs1061170. Differences among genotypes were analyzed via the chi-square test. Patients were evaluated with a neuropsychometric battery for CD 1 day and 1 month after CEA. A multiple logistic regression model was created. All variables with univariate p < 0.20 were included in the final model. RESULTS: The C5 genotypes A/G (OR 0.26, 95% CI 0.11-0.60, p = 0.002) and G/G (OR 0.22, 95% CI 0.09-0.52, p < 0.001) were significantly associated with lower odds of exhibiting CD at 1 day after CEA compared with A/A. The CFH genotypes C/T (OR 3.37, 95% CI 1.69-6.92, p < 0.001) and C/C (OR 3.67, 95% CI 1.30-10.06, p = 0.012) were significantly associated with higher odds of exhibiting CD at 1 day after CEA compared with T/T. Statin use was also significantly associated with lower odds of exhibiting CD at 1 day after CEA (OR 0.43, 95% CI 0.22-0.84, p = 0.01). No SNPs were significantly associated with CD at 1 month after CEA. CONCLUSIONS: The presence of a deleterious allele in the C5 and CFH SNPs may predispose patients to exhibit CD after CEA. This finding supports previous data demonstrating that the complement cascade system may play an important role in the development of CD. These findings warrant further investigation.

Statins reduce neurologic injury in asymptomatic carotid endarterectomy patients.

BACKGROUND AND PURPOSE: Statins are neuroprotective in a variety of experimental models of cerebral injury. We sought to determine whether patients taking statins before asymptomatic carotid endarterectomy exhibit a lower incidence of neurological injury (clinical stroke and cognitive dysfunction). METHODS: A total of 328 patients with asymptomatic carotid stenosis scheduled for elective carotid endarterectomy consented to participate in this observational study of perioperative neurological injury. RESULTS: Patients taking statins had a lower incidence of clinical stroke (0.0% vs 3.1%; P=0.02) and cognitive dysfunction (11.0% vs 20.2%; P=0.03). In a multivariate regression model, statin use was significantly associated with decreased odds of cognitive dysfunction (odds ratio, 0.51 [95% CI, 0.27-0.96]; P=0.04). CONCLUSIONS: Preoperative statin use was associated with less neurological injury after asymptomatic carotid endarterectomy. These observations suggest that it may be possible to further reduce the perioperative morbidity of carotid endarterectomy. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00597883.