Effect of Raised CBF During CEA on Cognition in DM Patients

Based on previous clinical studies, we have found that patients with diabetes mellitus (DM)
who are having carotid endarterectomy (CEA) have a four-fold higher incidence of cognitive
dysfunction, 1 day and 1 month after surgery, than a control group of elderly diabetic
patients having spine surgery.

We hypothesize that this increased incidence is due to sub-cortical ischemia associated with
the clamping of the ipsilateral carotid artery, because intra-operatively we rarely see EEG
changes, or a significant number of emboli upon clamping or unclamping the carotid artery,
or new cortical lesions of ischemia by MRI after surgery. In order to decrease cognitive
dysfunction in patients with DM, we propose to randomize them to either i) have a shunt
placed across the surgical site assuming it is surgically feasible or ii) be treated by
"conventional" management during which time a shunt is placed only in the unlikely event of
significant cortical ischemia determined by EEG, which occurs in about 5% of all cases.

The purpose of this study is to determine if patients with adult-onset diabetes mellitus
having the surgical procedure called carotid endarterectomy benefit from increasing blood
flow to the brain with a "shunt". A "shunt" is a tube inserted below and above the surgical
area at the time when the carotid artery is clamped to allow the surgeon to work in a
bloodless field and to supplement blood flow to the brain. Benefit is measured after surgery
by comparing performance on a battery of cognitive tests, which test your ability to perform
pencil-paper, memory and finger dexterity tests, to performance before surgery.

Patients in the shunt group whom the surgeon at the time of surgical exposure considers too
technically difficult to shunt, will not have a shunt inserted but will be treated
statistically as if they were shunted (intention to treat). Follow-up evaluations will be
performed 1 day, and 1 and 6 months after surgery so that the long-term effect of shunting
can be evaluated.

Cerebral injury will be determined in two ways.

First, all patients will be evaluated using a battery of neuropsychometric tests before and
after surgery. Patients admitted to the Irving Clinical Research Center (CRC) will have
their tests 1 day before, and 1 day, and 1 and 6 months after surgery. Those coming into the
hospital on the day of surgery, "Same Day", will be evaluated on the day of surgery. They
will be evaluated 1 day, and 1 and 6 months after surgery.

Preoperative neurological and neuropsychological evaluation will be performed. The
neuropsychometric tests are not intended to be diagnostic of specific neuropsychiatric
disorders, but rather are designed to demonstrate general neuropsychological pathology.
These tests can be divided into four types: (1) an evaluation of language, (2) an evaluation
of speed of mental processing, (3) an evaluation of ability to learn using a list of words,
and (4) an evaluation of visual perception requiring a patient to copy a complex figure.
Before the battery is administered we will assess each patient's level of pain while sitting
and standing using a 10 point Visual Analog Scale and gauge their mood with a series called
the Wong/Baker Faces Rating scale. Patients having spine surgery may have significant pain
before surgery which might impair their performance.

We will also be measuring Quality of Life (QOL) in all enrolled patients.

This will be done using two well-known examinations (Telephone Interview for Cognitive
Status (TICS) and Centers for Disease Control and Prevention Health-Related Quality-of-Life
14Item Measure (CDC HRQOL14)) and a series of questions investigating how well patients are
able to perform activities of daily living (ADLs) and instrumental activities of daily
living (IADLs). These tests will be given at two time points, once before the surgery and
then one month after surgery. We will look for changes in quality of life that may correlate
with neuropsychometric test performance.

Second, peripheral serum samples will be drawn before induction, before crossclamping the
carotid artery, 15 minutes after crossclamping the carotid artery and 24 hours after
surgery.

Since the purpose of this study is to determine if a change in "conventional" management
will improve patient's ability to perform our battery of neuropsychometric tests, we will
randomly assign patients to either receive a "shunt" prophylactically if the surgeon
determines that it is technically safe, even if conventional management does not indicate
its necessary, or a "shunt" only if it is indicated by EEG, "conventional" management.
Subjects in the prophylactic group will receive a shunt even when by standard criteria they
would not need to receive one. Randomization will be performed in blocks of four patients
each using a randomization table. Using "block" randomization we will increase the
probability of an equal number of patients "shunted" or not shunted. The surgeon will be
told which group the patient has been randomized into after induction and prior to clamping
the carotid artery.

Inclusion Criteria:

- ability to speak English

- no history of permanent neurological impairment, Axis I psychiatric diagnosis or
drug abuse.

- scheduled for elective carotid endarterectomy for treatment of carotid artery
stenosis.

- diagnosed with diabetes mellitus or HbA1c value greater than 10%

Exclusion Criteria:

- younger than 18 yrs.