Does Cognitive Dysfunction after Carotid Endarterectomy Vary by Statin Type or Dose?

Abstract Our prev ious work demonstrates that asymptomatic carotid endarterectomy (CEA ) patients demonstrate less perioperative neurologic in jury, defined as stroke and early cognitive dysfunction (eCD) observed within 24h r of CEA, when taking statins pre-operatively. This study examines whether the incidence of eCD observed 24hr after asympto matic CEA varies as a function of statin type or dose. Patients with asymptomatic carotid stenosis scheduled for CEA consented to participate in an observational IRB-approved study (N=324). Pat ients were evaluated with an extensive battery of neuropsychometric tests pre-operatively and 24hr post-operatively. Of the 324 consented patients, 200 were taking statins. Patients taking pravastatin and fluvastatin exhib ited no eCD, while patients taking lovastatin (17.7%) and rosuvastatin (16.7%) exh ib ited incidences of eCD similar to those not taking statins (20.2%). Patients taking simvastatin exhib ited a significantly lower incidence of eCD than those taking atorvastatin (3.0% vs. 16.0%, P=0.005). Patients taking a maximal dose of any statin exhib ited a significantly lower incidence of eCD than patients taking sub-maximal doses (2.7% vs. 15.9%, P=0.002). These observations suggest that the incidence of eCD may in fact vary as a function of statin type and that maximal doses may be the optimal dose for patients undergoing CEA. This variation may be due to the physico-chemical properties of statins such as lipophilicity, molecu lar size, and b lood brain barrier penetrability. These findings should be used to inspire randomized prospective work to determine the safety, feasibility, and outcomes of optimizing statin use prior to CEA

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 [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

White Matter Hyperintensities in Older Adults and Motoric Cognitive Risk Syndrome

Motoric cognitive risk (MCR) syndrome is a recently described pre-dementia syndrome characterized by slow gait and cognitive complaints that has been implicated as a predictor of cognitive decline and dementia in older adults. Previous work suggests that cerebrovascular disease is associated with MCR. White matter hyperintensities (WMH) are postulated to be a product of cerebrovascular disease, and have been associated with impaired mobility and impaired cognition. This study aimed to determine if MCR is associated with regional WMH

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   (Stroke. 2013;44: 1150-1152.