Assessing Neurocognition After Cerebrovascular Intervention
Assessing Neurocognition After Cerebrovascular Intervention
Decreased blood flow to the brain can cause decreased cognitive function. Carotid disease can
 result in decreased blood flow to the brain. The investigators seek to assess this
 relationship prospectively through performing a battery of neurocognitive assessments,
 collection of serum markers of inflammation, and through neuroimaging at two points before
 intervention (2 months and 1 month before stenting) and at two points after intervention (1
 month and 2 months after intervention). The goal is to provide prospective evidence to
 identify the extent to which carotid stenosis and hypoperfusion of the brain results in
 diminished neurocognitive performance, and see if serum biomarkers before and after stenting
 correlate with these findings.
Patients are being asked to partake in this study because the PI has decided on clinical
 grounds as outlined in the clinical trial, NASCET, (either asymptomatic 70% carotid stenosis
 or symptomatic >50% carotid stenosis) that CAS or CEA is indicated. The only aspect of the
 study that is research is the cognitive testing, the inflammatory blood markers, and
 components of the neuroimaging.

 In this pilot study 20 patients, undergoing CAS for CS, will undergo cognitive testing at 2
 time points before intervention (1 months, and 2 months) and at 2 time points after invention
 (1 month and 2 months). The two preoperative time points will serve as the control group and
 the two postoperative time points will serve as the intervention group.

 Patients, as outlined by NASCET criteria, will have between 50% symptomatic stenosis or 70%
 asymptomatic stenosis of the carotid artery. If patients present acutely or are otherwise
 clinically determined to be unstable (e.g. crescendo TIAs, intolerance of normal physiologic
 blood pressure, etc.) due to their carotid disease, they will excluded from the study.

 Patients will serve as their own controls, classifying the study as a within-subjects design.
 Patients will also have venous blood drawn to ascertain the change in serum markers
 associated with endothelial dysfunction and inflammation before and after intervention.
 Finally, patients will have magnetic resonance imaging (MRA) one month before intervention
 and 2 months after intervention in order to assess changes in global cerebral blood flow.

 The following neurocognitive tests will take place - the duration of all typically takes one
 hour to complete.

 1. Memory measured with the Hopkins Verbal Learning Test-Revised (HVLT-R) and Rey Complex
 Figure

 2. Executive function assessed with Trails A and B

 3. Attention/processing speed measured with Wechsler Adult Intelligence Scale Digit Span
 and Coding subtests

 4. Language assessed with the Multilingual Naming Test and Verbal Fluency

 5. Visuospatial abilities measured with Block Design

 6. Global cognition measured with Mattis Dementia Rating Scale

 7. Estimated premorbid intelligence measured with the American version of the National
 Adult Reading Test (preoperatively only)

 8. Mood assessed with the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory
 (BAI) Biomarkers, as a proxy for systemic inflammation will also be collected. The
 following biomarkers are associated with inflammation-TNF-α, IL-6, IL-1β, CRP, IFN-γ and
 endothelial cell activation-sICAM sVCAM will be obtained from venous blood (5 ml) and
 stored at -80° C until the time of electrochemiluminescence assay. As an accompanying
 measurement of inflammation, complete blood counts will be assessed.

 R statistical software will be used for the statistical analysis. Fisher exact, chi square,
 and logistic regression testing will be used to assess categorical data while paired t tests
 and linear regression models will be used to assess continuous variables. Multivariable
 univariate logistic and linear regression will be performed to assess if carotid intervention
 is associated with statistically significant changes in neurocognitive performance or changes
 in serum biomarker levels.

 Additional predictors to assess neurocognitive performance will include age, gender, race,
 degree of carotid stenosis, side of stenosis, prior history of stroke, prior history of
 neurosurgical or endovascular interventions, presence of coronary artery disease, active
 malignancy, vasculopathy including diabetes, hypertension, hyperlipidemia, obesity, systemic
 vascular disease, intracranial atherosclerosis, ultrasound perfusion of intracranial vessels,
 prior neurocognitive decline: ie prior history of Alzheimer's, degenerative neurological
 disease. Outcome variables will include standardized neuropsychological measures. The
 investigators hypothesize a more exuberant neurocognitive response in patients with an
 incomplete circle of Willis.

 A dropped model will be performed to prevent overfitting of the regression analysis. A p
 value less than 0.05 will be used to define statistical significance.

 The investigators predict that patients will not have a statistically significant change in
 neurocognitive performance during the three-month and six-week time points prior to
 intervention-and this will serve as the control period. We predict that 35% of patients will
 have some improvement in neurocognition after intervention. The sample size calculator to
 identify a difference in groups at a p<0.05 with a power of 0.8 predicts with 5% attrition
 determines that 20 patients will be required for the analysis.
Inclusion Criteria:

 -  patients >18 years of age

 -  ultrasound evidence of carotid stenosis; in which the patient has either 50% or
 greater symptomatic carotid stenosis or 70% or greater asymptomatic carotid stenosis.

 Exclusion Criteria:

 1. patients <18 years of age

 2. patients with without compatibility for MRI

 3. patients requiring carotid stenting for reasons not related to long-standing stenosis

 4. patients requiring emergency carotid stenting for acute symptoms such as crescendo
 transient ischemic attacks, intolerance of physiologic blood pressure.

 5. Patients that do not have appropriate capacity (i.e. understand the risks and benefits
 associated with this study) or are unable to consent for themselves will not be
 included in this study.