From the Eastern Vascular Society

Cognitive changes after surgery vs stenting for

carotid artery stenosis
Brajesh K. Lal, MD,a Maha Younes, PhD,b Gina Cruz, APN,c Indu Kapadia, PA,c Zafar Jamil, MD,c and
Peter J. Pappas, MD,c Baltimore, Md; and Newark, NJ

Objectives: Cognitive function has not been evaluated systematically in the context of carotid endarterectomy (CEA)
versus carotid artery stenting (CAS). Cognitive decline can occur from microembolization or hypoperfusion during CEA
or CAS. Carotid revascularization may, however, also improve cognitive dysfunction resulting from chronic hypoperfu-
sion. We compared cognitive outcomes in consecutive asymptomatic patients undergoing CAS or CEA.
Methods: This is a prospective nonrandomized single-center study of patients with asymptomatic carotid stenosis >70%
undergoing CAS or CEA using standard techniques. Neurologic symptoms were evaluated by history, physical
examination, and the National Institutes of Health Stroke Scale. A 50-minute cognitive battery was performed 1 to 3 days
before and 4 to 6 months after CEA/CAS. The tests (Trail Making Tests A/B, Processing Speed Index (PSI) of the
Wechsler Adult Intelligence Scale – Third Edition (WAIS-III), Boston Naming Test, Working Memory Index (WMI) of
the Wechsler Memory Scale ⴚ Third Edition (WMS-III), Controlled Oral Word Association, and Hopkins Verbal
Learning Test) for six cognitive domains (motor speed/coordination and executive function, psychomotor speed,
language (naming), working memory/concentration, verbal fluency, and learning/memory) were conducted by a
neuropsychologist. The primary analysis of impact of treatment modality was a normalized cognitive change score.
Results: Forty-six patients underwent prepost testing (CEA ⴝ 25, CAS ⴝ 21). Women comprised 36% of the cohort, mean
preprocedural stenosis was 84%, and 54% were right-sided lesions. All patients were successfully revascularized without
periprocedural complications. The scores for each test improved after CEA except WMI, which decreased in 20 of 25
patients. Improvement occurred in all tests after CAS except PSI, which decreased in 18 of 21 patients. In addition to
comparing the changes in individual test scores, overall cognitive change was measured by calculating the change in
composite cognitive score (CCS) postprocedure versus baseline. To compute the CCS, the raw scores from each test were
transformed into z scores and then averaged to calculate each patient’s composite score. The composite score at baseline
was then compared with that from the postprocedure testing. The CCS improved after both CEA and CAS, and the
changes were not significantly different between the groups (.51 vs .47; P ⴝ NS).
Conclusions: Carotid revascularization results in an overall improvement in cognitive function. There are no differences in
the composite scores of five major cognitive domains between CEA and CAS. When individual tests are compared, CEA
results in a reduction in memory, while CAS patients show reduced psychomotor speed. Larger studies will help confirm
these findings. ( J Vasc Surg 2011;54:691-8.)

Cognitive function is being increasingly recognized as
an important outcome measure that affects patient well-
being, functional status, and quality of life.1-3 Almost 30%
of patients may experience cognitive impairment after car-
diac surgery.4 This has stimulated extensive research to
establish standards of prevention,5 management,5 testing,6
and reporting7 of cognitive impairment after cardiac sur-
gery. However, cognitive function has not been evaluated
systematically in the context of carotid revascularization.
From the Division of Vascular Surgery, University of Maryland Medical
Center, Baltimorea; the Division of Neuropsychology, Department of
Psychiatryb and the Division of Vascular Surgery,c UMDNJ-New Jersey
Medical School, Newark.
Supported by a grant from the American Heart Association (B.K.L.).
Competition of interest: none.
Presented at the Twenty-third Annual Meeting of the Eastern Vascular
Society, Philadelphia, Pa, September 24-26, 2009.
Reprint requests: Brajesh K. Lal, MD, University of Maryland Medical
Center, 22 S. Greene St., S10B00, Baltimore, MD 20212 (e-mail: blal@
smail.umaryland.edu).
The editors and reviewers of this article have no relevant financial relationships
to disclose per the JVS policy that requires reviewers to decline review of any
manuscript for which they may have a competition of interest.
0741-5214/$36.00
Copyright © 2011 by the Society for Vascular Surgery.
doi:10.1016/j.jvs.2011.03.253
Clinical investigations designed to contrast the efficacy of
carotid endarterectomy (CEA) versus best medical therapy,
and CEA versus carotid artery stenting (CAS) in patients
with carotid artery stenosis have only been based on the
traditional end points of stroke, myocardial infarction
(MI), and death.
A decline in cognitive function could occur during
carotid revascularization from microembolic ischemia dur-
ing surgical dissection (CEA) or intravascular instrumenta-
tion (CAS). It could also occur from hypoperfusion during
clamping (CEA) or balloon dilation (CAS). Conversely,
restoring perfusion may improve cognitive dysfunction that
may have occurred from a state of chronic hypoperfusion. It
is not known whether these complex interactions ultimately
result in a net improvement or deterioration of cognitive
function. Furthermore, it is not known whether the two
methods of carotid revascularization have a differential effect
on cognitive outcome. It is well-known though, that there is a
positive relationship between improvement in cognition and
improvement in functional outcome of patients.1,3
The reviews of Lunn et al8 and Irvine et al9 exemplify
the current absence of consensus regarding cognitive out-
come after CEA. They found that 16 of 28 studies demon-
691

692 Lal et al
strated cognitive improvement after CEA. The remaining
12 studies showed no improvement or a decline.
Ghogawala et al identified 17 additional studies that pro-
vided follow-up cognitive data for at least 1 month after
carotid revascularization and found equally conflicting re-
sults. There are even fewer studies addressing cognitive
outcome after CAS,10-14 and they have variously reported a
decline, improvement, or no change in cognitive function
after the procedure. These conflicting results may, in part,
be explained by the sample sizes, short duration of follow-
up, variability in the timing of cognitive assessment, the
types of cognitive tests used, types of cognitive domains
tested, use of comparators, absence of baseline assessments,
and significant variability of severity of stenosis or pre-
existing neurological symptoms in patients.
Only two studies have compared cognitive outcomes
between surgical and endovascular carotid revasculariza-
tion.10,11 However, they used limited cognitive testing on
a mixed cohort of symptomatic and asymptomatic patients,
and a significant proportion of patients underwent angio-
plasty without stenting in the endovascular arm of the
cohort. One other study compared stenting to CEA but
used a limited cognitive evaluation restricted to left-
hemispheric functions alone (the Mini Mental State Exam-
ination) and did not find any differences.12 No formal
assessment of cognitive function has been made in prior or
recent randomized trials comparing revascularization strat-
egies for carotid stenosis.15-18 There is a strong need for
such an evaluation to test whether carotid revascularization
does indeed have an effect beyond prevention of stroke.
Furthermore, since the major North American carotid trial
failed to show a difference in combined stroke, MI and
death rate between CAS and CEA,17 the superiority of a
procedure may be predicated on cognitive outcome.
In this study, we developed, implemented, and evalu-
ated a unique battery of cognitive tests designed specifically
for patients with carotid stenosis. The battery was imple-
mented in patients with asymptomatic high-grade carotid
stenosis undergoing revascularization (CEA or CAS) at
baseline and 4 to 6 months postprocedure. A standard-
ized change score of the average of all the tests at baseline
versus postprocedure testing served as the primary anal-
ysis of impact on cognition. A secondary analysis com-
pared change scores for separate cognitive domains eval-
uated by individual tests.
METHODS
Patients and study design. This was a prospective
nonrandomized single-center study of patients with asymp-
tomatic primary carotid stenosis ⱖ70% undergoing CAS or
CEA using standard techniques. Patients were recruited at
Saint Michael’s Medical Center. Since stroke is known to be
associated with cognitive impairment, and since stroke may
interfere with the performance of certain cognitive tests
even in the absence of a cognitive deficit, we did not recruit
symptomatic patients in this study.19 Only patients without
neurological symptoms of a stroke, transient ischemic at-
tack or amaurosis fugax were considered for the study.
JOURNAL OF VASCULAR SURGERY
September 2011
Patients with medical conditions limiting life expectancy
(⬍1 year) or interfering with outcome evaluations were
excluded. Duplex ultrasonography was utilized to assess the
degree of carotid stenosis using modified Washington Uni-
versity velocity criteria published and validated by our
group previously.20 Neurologic assessment involved a his-
tory, physical examination, and the National Institutes of
Health Stroke Scale21 implemented by a qualified vascular
surgeon. Patients were evaluated at baseline within 1 to 3
days prior to their revascularization procedure and again at
4 to 6 months after revascularization.
Carotid revascularization procedures. All physicians
were fellowship trained in Vascular and Endovascular Sur-
gery. The Division’s protocol for CEA is standardized for
general anesthesia, surgical incision, intraoperative moni-
toring, the use of a shunt, and patch angioplasty.22 The
protocol for CAS is also standardized, including local anes-
thesia, periprocedural monitoring, use of an embolic pro-
tection device, mandatory stenting, and the use of antico-
agulation and antiplatelet agents.20 The selection of the
type of revascularization (CEA or CAS) to be utilized in
each patient was according to patient/surgeon preference
and was not influenced by the study.
Cognitive testing protocol. The National Institute of
Neurological Disorders-Canadian Stroke Network (NINDS-
CSN) harmonization standards for testing vascular cogni-
tive impairment,23 previous experience from the assess-
ment of cognitive function in cardiac surgery,7,24
medical treatment outcomes studies,25 and carotid re-
vascularization studies8-14 were utilized to select the test
battery. These reports emphasize testing within specific
cognitive domains with an analysis of both composite
and domain-specific outcomes.26 They also recommend
follow-up testing remote from the intervention to avoid
confounding the results with periprocedural medications
and/or stress.
A 50-minute cognitive battery was performed 1 to 3
days before and 4 to 6 months after CEA/CAS. The tests27
for six cognitive domains (motor speed/coordination and
executive function, psychomotor speed, language [nam-
ing], working memory/concentration, verbal fluency, and
learning/memory) were conducted by a neuropsycholo-
gist. We selected tests that were broadly accepted cognitive
measures with standardized administration procedures and
well-documented validity, accuracy, and reliability statis-
tics.27 All patients underwent all cognitive tests. The
order of test administration was constant for baseline and
follow-up evaluations. Tests were conducted in a quiet
room. The order of administration accommodated the
delays required for recall intervals and minimized stimuli
interference in memory tasks.
Cognitive testing battery.
1. Trail Making Test (TMT)28 is a two-part test of motor
speed/coordination and executive function. The first
part, Trails A, requires the subject to draw lines to connect
numbered circles, in consecutive order, that are randomly
arranged on a page. In Trails B, the subject connects
JOURNAL OF VASCULAR SURGERY
Volume 54, Number 3
randomly arranged, numbered and lettered circles by alter-
nating between them (1, A, 2, B, 3, C, etc.). The test is
timed and the subject is urged to connect the circles “as fast
as you can” without lifting the pencil from the paper. The
score for each test is the total time to completion.
2. Processing Speed Index is a subset of the Wechsler
Adult Intelligence Scale-Third Edition (WAIS-III)29
and can measure psychomotor speed. Digit Symbol
Coding requires the patient to quickly match and copy a
series of symbols to a series of numbers. Symbol Search
requires the patient to assess a series of stimuli to deter-
mine if a given target is present. Both of these tests
require the patient to do as many items as possible in 2
minutes. The number of items completed is the score.
3. Boston Naming Test30 is a language task used to assess
the ability to name pictured objects. It consists of 60
line-drawn objects of graded difficulty ranging from
“bed” to “abacus.” The pictures are presented one at a
time on cards, and two prompting cues can be given if
the subject does not produce the word spontaneously.
The score is the total number of correct words given
without a phonemic cue.
4. Working Memory Index is part of the Wechsler Mem-
ory Scale-Third Edition (WMS-III)31 composed of the
Letter-Numbering Sequencing and the Spatial Span
tests to assess working memory/concentration. The
Letter-Number sequencing test requires the patient to
repeat back a series of random numbers and letters in
ascending order (numbers) and alphabetical order. The
task gets increasingly difficult as more numbers and
letters are added. Spatial Span requires the subject to
point to a series of blocks in an array in the same order
that the examiner does and later in the reverse order
from the examiner.
5. Controlled Oral Word Association Test (COWA)32
assesses verbal fluency in three word-naming trials. Each
1-minute trial requires the production of words begin-
ning with a given letter (F, A, S; excluding proper names
and the same word with a different suffix) with the test
score equaling the sum of all acceptable words.
6. Hopkins Verbal Learning Test (HVLT-revised)33 is
a word-list learning task used to assess a subject’s ability
to recall a list of words after a delay. Over three trials, a
12-word list of three semantic categories is presented to
the subject who then recalls as many words as possible,
in any order. After a 20-minute delay, a recall trial is
administered. The score is the total number of words
recalled after the delay. Six parallel forms are available.
Statistical analysis. The first step in generating the
overall composite cognitive score was to transform the raw
test score of each patient into a z score by using the mean
and standard deviation for that test in all the patients so that
the z score ⫽ (x –m)/␴; where x ⫽ the raw score for the
test, m ⫽ mean score of the test for the entire cohort, and
␴ ⫽ the standard deviation of the test score for the entire
cohort. The z scores of each test were then summed and
divided by the total number of tests to calculate the pa-
Lal et al 693
Table I. Demographic features of patients undergoing
CAS and CEA for asymptomatic high-grade carotid artery
stenosis
CAS CEA
Feature n ⫽ 21 n ⫽ 25 P
Female gender 38% 32% NS
Right-sided lesion 57% 56% NS
Percent stenosis (mean) 82% 88% NS
Hypertension 42% 32% NS
Coronary artery disease 62% 56% NS
Hypercholesterolemia 67% 76% NS
Diabetes 38% 28% NS
CAS, Carotid artery stenting; CEA, carotid endarterectomy; NS, not significant.
tient’s composite score (CS) so that CS ⫽ ⌺ z ⫺ scores/n;
where n ⫽ total number of tests performed in the patient.
CS was calculated at baseline and at follow-up. The change
in each patient’s standardized composite score from base-
line to follow-up was used as the primary endpoint in this
study. The average change in composite score for patients
undergoing CAS was then compared to that in patients
undergoing CEA.
Since a group analysis combining the scores of all the
tests across multiple domains may not be sensitive to
changes in one particular cognitive domain (ie, an improve-
ment in one domain may cancel out a decline in another
domain), a secondary analysis involved a comparison of
change scores of each individual test.
RESULTS
Patient demographics. Forty-six patients with pri-
mary carotid artery stenosis agreed to participate in this
study and completed pre- and postprocedural cognitive
testing. Of these, 25 patients underwent CEA, and 21
underwent CAS. Women comprised 36% of the cohort, the
mean preprocedural stenosis was 84%, and 56% were right-
sided lesions. These and other risk factor distributions were
not significantly different between the two groups of pa-
tients (Table I). The CAS group had embolic protection in
all cases, and the Abbott Acculink, Accunet system (Abbott
Park, IL) was utilized in all instances. All patients were
successfully revascularized without periprocedural stroke,
MI, or deaths. Patients were followed for a mean of 5.2
months (range, 4-6 months).
Cognitive outcomes. The composite and domain-
specific cognitive outcomes are summarized in Table II.
The composite change score for the entire test battery
improved in patients both after CEA and after CAS when
compared to their baselines. However, the changes were
not significantly different between the two groups (⫹0.51
vs ⫹0.47; P ⫽ ns).
When individual test results were evaluated to assess the
outcome of individual cognitive functional domains
(Fig 1), the scores improved for each test after CEA except
the Working Memory Index. This test measures working
memory/concentration and was found to be decreased in
 JOURNAL OF VASCULAR SURGERY
694 Lal et al September 2011

Table II. Standardized cognitive change scores (follow-up vs baseline) in patients undergoing CAS and CEA for
asymptomatic high-grade carotid artery stenosis

Raw scores Change score

CAS CEA CAS CEA
Pre-op Post-op Pre-op Post-op
Cognitive function test Domain (SD) (SD) P (SD) (SD) P n ⫽ 21 n ⫽ 25 P

Trail Making Test A Motor speed/coordination 121 (22) 120 (19) .44 138 (26) 129 (21) .04 0.63 0.74 NS
and B and executive function
Processing Speed Index Psychomotor speed 107 (16) 102 (16) .24 106 (13) 144 (14) .12 ⫺0.32 0.58 .001
Boston Naming Test Language (naming) 52 (8) 57 (9) .11 56 (10) 63 (7) .06 0.59 0.66 NS
Working Memory Working memory/ 100 (16) 108 (12) .13 103 (15) 97 (12) .17 0.46 ⫺0.41 .001
Index concentration
Controlled Oral Word Verbal fluency 38 (9) 44 (9) .07 39 (11) 46 (11) .09 0.69 0.61 NS
Association Test
Hopkins Verbal Learning/memory 7.9 (2.0) 9.4 (1.9) .05 8.1 (1.7) 9.6 (2.1) .05 0.77 0.86 NS
Learning Test
Composite for all tests 0.47 0.51 NS
NS, not significant; SD, standard deviation.
A positive change score indicates improvement in cognitive function after the procedure, a negative score indicates deterioration.

Fig 1. Change (follow-up vs baseline) in the cognitive scores of a composite of all domains tested, and of each
individual test, in patients undergoing carotid artery stenting (CAS) and carotid endarterectomy (CEA) for asymp-
tomatic high-grade carotid artery stenosis. A positive change score indicates improvement in cognitive function after
the procedure, a negative score indicates deterioration.

20 of 25 patients after CEA but was improved after CAS
(P ⫽ .001). The scores for each cognitive test improved
after CAS, except the Processing Speed Index, which de-
creased in 18 out of 21 patients. This test measures psy-
chomotor speed and was improved after CEA (P ⫽ .001).
DISCUSSION
In this nonrandomized study of neurologically asymp-
tomatic patients with high-grade carotid stenosis ⱖ70%,
carotid revascularization resulted in an overall improve-
ment in cognitive function. There were no differences in
the composite scores of six major cognitive domains be-
tween patients undergoing CEA versus CAS. When indi-
vidual tests were compared, CEA resulted in a reduction in
memory, while CAS patients showed reduced psychomotor
speed.
Cognitive function is the term used to describe how a
person produces and controls behavioral and mental pro-
cesses such as thinking, learning, remembering, problem
solving, and consciousness. Conversely, a neurologic deficit
is associated with a loss of localized sensory or motor
function. The two types of deficits may occur alone or
concurrently. There is clear evidence for the coexistence of
cognitive deficits in patients with stroke from carotid ste-
nosis.19 However, a subset analysis of the Cardiovascular
Health Study suggests that carotid stenosis may be a risk
factor for cognitive impairment even in the absence of
strokes.34 Of the 4,006 patients in that study, 32 were
identified with asymptomatic carotid stenosis ⱖ75%. These
patients, along with the rest of the cohort, were serially
tested with a modified mini-mental state examination.
There was a significant decline in cognitive function in 34%
JOURNAL OF VASCULAR SURGERY
Volume 54, Number 3 Lal et al 695

of the carotid stenosis patients over 5 years. Such a decline

was not observed in the remaining cohort. In our study,
carotid revascularization (by CEA or CAS) resulted in
improved cognition. This indicates that revascularization
may serve the dual function of preventing neurologic as
well as cognitive decline in patients with carotid stenosis.
Cognitive outcomes must be strongly considered as an
additional outcome measure when future trials are de-
signed to evaluate the optimal treatment (revascularization
or pharmacologic) of neurologically asymptomatic pa-
tients.
While neurologic examinations focus on specific sen-
sory or motor deficits, cognitive assessments examine a set
of more-or-less independent functional domains.24 Most
tests are designed to test individual domains, but some may
examine combined categories. All cognitive tests used in
our study have standardized administration procedures
with appropriate normative comparison groups. Guidelines
for the assessment of cognition in cardiac surgery7,24 and
medical treatment outcomes studies25 have been pub-
lished. However, a cognitive battery of tests specifically
addressing the unique issues relating to carotid stenosis has
not been devised. Our study reports on a cognitive test
battery that is comprehensive and responsive to the unique
subset of carotid stenosis patients, while maintaining clin-
ical feasibility (takes approximately 50 minutes to com-
plete). The selected tests are sensitive to changes in six
major cognitive domains that have been reportedly
affected in patients with vascular disease and carotid
stenosis.7-14,23-25
Crawley et al compared cognitive outcome in 20 pa-
tients undergoing carotid angioplasty without stenting and
26 patients undergoing CEA.10 At 6 weeks, five patients in
each group had an equivalent decline in cognitive perfor-
mance. Another study based on the same cohort of patients
(Carotid and Vertebral Artery Transluminal Angioplasty
Study, CAVATAS)15 also demonstrated an equivalent de-
cline in cognitive performance in both groups of patients.11
These early studies highlighted the likelihood of cognitive
consequences from carotid angioplasty. However, endo-
vascular carotid revascularization methodology has since
evolved, and currently includes mandatory stenting with
embolic protection in all patients treated for primary ath-
erosclerosis.35
The current standard CAS methodology was utilized
in a more recent study of 40 patients.12 Based on a
mini-mental state examination, the authors reported a

4™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™
Fig. 2. Representative diffusion-weighted magnetic resonance
images of the brain before and after carotid artery stenting (CAS)
demonstrating a silent cortical microinfarct that did not manifest as
a frank neurologic deficit on thorough neurological examination.
A, Preprocedure diffusion-weighted coronal view. B, Preproce-
dure fluid-attenuated inversion-recovery (FLAIR) transverse im-
age. C, Preprocedure diffusion-weighted transverse view. D, Dif-
fusion-weighted transverse view obtained 24 hours postcarotid
stenting. Note new infarction (circled).

696 Lal et al
trend toward improvement in cognitive outcome after
CAS. The study received widespread reportage in the
media36; however, the cognitive battery utilized focused
primarily on left hemispheric cognitive functions and
patients with prior stroke (vs asymptomatic patients), or
patients with primary atherosclerosis (vs smooth, post-
CEA restenosis) were not separated out, thereby pre-
cluding any firm conclusions.
Our study compared CAS and CEA performed using
the current standard of care on a more consistent cohort
of asymptomatic patients with primary atherosclerosis.
The cognitive tests comprising our battery were selected
to assess multiple domains affected by right, left, or both
hemispheres, and to assess domains that have been con-
sistently reported to be affected in patients with vascular
disease and carotid artery stenosis. Our results are there-
fore likely to be reliable and applicable to current prac-
tice.
The notion that carotid artery disease can produce
cognitive impairment or a dementia state, was first pro-
posed by Dr Fisher in 1951, based on a necropsy case.37 He
proposed that restoration of blood supply could reverse the
condition. Improved cerebral blood flow has subsequently
been shown to translate into improved cognitive out-
come.38-40 Our results indicate that composite cognitive
function improves after revascularization regardless of the
method utilized (CAS or CEA) and are consistent with
Fisher’s original hypothesis.
Cerebral microinfarctions in the form of white matter
or cortical lesions correlate with poor cognition.41,42 In
experimental studies, injection of 50-␮m microspheres into
rat carotid arteries resulted in cerebral injury and reduced
attentional performance.43 Manipulation of the carotid
artery during surgical or endovascular revascularization
causes atheroembolization with consequent silent cerebral
microinfarction.44 Transcranial Doppler monitoring has
identified approximately 1000 microemboli during CAS
while CEA is associated with eight to 17 times fewer
microemboli.44,45 Consistent with the microembolization
rates, CAS results in cerebral microinfarctions more fre-
quently than CEA (54% vs 17%).46 One such microinfarct
in a post-CAS patient from our study is demonstrated in Fig
2. While the neurological complication rates between CAS
and CEA may not differ dramatically, these reports raise a
justifiable concern that silent microembolic cerebral injury
with consequent cognitive decline may occur more fre-
quently after CAS compared with CEA.
The fact that cognition, on average, was no different
between the two groups argues against a clinical signifi-
cance for the observed differences in microemboli and
microinfarctions between the two procedures. One study
has reported reduced microinfarction rates in patients un-
dergoing CAS with embolic protection versus unprotected
CAS (26% vs 36%).47 Therefore, it is possible that the
addition of anti-embolic devices may reduce cognitive in-
jury from CAS.
Despite the improvement in composite function, each
procedure adversely affected one unique cognitive domain.
JOURNAL OF VASCULAR SURGERY
September 2011
This interesting observation argues in favor of distinct
injury patterns in each of the two procedures. Emboli
released during CEA tend to be larger in size despite being
less numerous. It is possible that these stream preferentially
to areas critical to memory functions. Conversely, the more
numerous but smaller emboli associated with CAS may
distribute to the more globally controlled process of psy-
chomotor speed.
LIMITATIONS
This is a nonrandomized study with patient alloca-
tion to treatment groups made on the basis of physician–
patient preference and is therefore subject to selection
bias. In view of the limited cohort and lack of differences
in baseline characteristics, we did not perform a regres-
sion analysis. However, based on demographic compar-
isons, the two cohorts did not differ significantly, and
important conclusions can therefore be derived from the
results. Importantly, baseline cognitive test results did
not differ significantly between the two groups, implying
that they started with a similar cognitive status. The
cohort studied is small, and the results are therefore
subject to Type II error. However, in the absence of an
established cognitive testing battery and a comparison of
their results and standard deviations in patients with CAS
versus CEA, a power analysis with calculation of number
of patients required to be tested was not possible. The
results of this study provide this information, and vali-
date a carotid disease-specific cognitive test battery, for
facilitating future larger trials.
CONCLUSIONS
Individuals with cognitive deficits are at greater risk for
problems with employment, activities of daily living, driv-
ing, social interactions, and family relationships. They also
incur significantly higher costs related to personal assis-
tance.1,3 Reported and ongoing studies on carotid stenosis
have not included cognitive outcome as an endpoint. Our
results indicate a potentially beneficial effect on cognition
after carotid revascularization and emphasize the need
for larger studies to confirm these findings. Our results
argue in favor of incorporating cognitive testing in future
clinical trials and in clinical practice related to carotid
artery stenosis.
AUTHOR CONTRIBUTIONS
Conception and design: BL
Analysis and interpretation: BL, MY
Data collection: BL, MY, GC, IK, PP, ZJ
Writing the article: BL
Critical revision of the article: BL, MY, GC, IK, PP, ZJ
Final approval of the article: BL, MY, GC, IK, PP, ZJ
Statistical analysis: BL, MY
Obtained funding: BL
Overall responsibility: BL
JOURNAL OF VASCULAR SURGERY
Volume 54, Number 3
REFERENCES
1. Chaytor N, Schmitter-Edgecombe M. The ecological validity of neuro-
psychological tests: a review of the literature on everyday cognitive skills.
Neuropsychol Rev 2003;13:181-97.
2. Tatemichi TK, Paik M, Bagiella E, Desmond DW, Pirro M, Hanzawa
LK, et al. Dementia after stroke is a predictor of long-term survival.
Stroke 1994;25:1915-9.
3. Rao SM, Leo GJ, Ellington L, Nauertz T, Bernardin L, Unverzagt F, et
al. Cognitive dysfunction in multiple sclerosis. II. Impact on employ-
ment and social functioning. Neurology 1991;41:692-6.
4. Baker RA, Andrew MJ, Knight JL. Evaluation of neurologic assessment
and outcomes in cardiac surgical patients. Semin Thorac Cardiovasc
Surg 2001;13:149-57.
5. Murkin JM. Neurocognitive outcomes: the year in review. [Miscella-
neous]. Cur Opin Anæsth 2005, Febr;2005:57-62.
6. Scott RB, Farmer E, Smiton A, Tovey C, Clarke M, Carpenter K, et al.
Methodology of neuropsychological research in multicenter random-
ized clinical trials: a model derived from the International Subarachnoid
Aneurysm Trial. Clin Trials 2004;1:31-9.
7. Murkin JM, Newman SP, Stump DA, Blumenthal JA. Statement of
consensus on assessment of neurobehavioral outcomes after cardiac
surgery. Ann Thorac Surg 1995;59:1289-95.
8. Lunn S, Crawley F, Harrison MJ, Brown MM, Newman SP. Impact of
carotid endarterectomy upon cognitive functioning. A systematic re-
view of the literature. Cerebrovasc Dis 1999;9:74-81.
9. Irvine CD, Gardner FV, Davies AH, Lamont PM. Cognitive testing in
patients undergoing carotid endarterectomy. Eur J Vasc Endovasc Surg
1998;15:195-204.
10. Crawley F, Stygall J, Lunn S, Harrison M, Brown MM, Newman S, et al.
Comparison of microembolism detected by transcranial Doppler and
neuropsychological sequelae of carotid surgery and percutaneous
transluminal angioplasty. Stroke 2000;31:1329-34.
11. Sivaguru A, Gains P, Beard J, Venables G. Neuropsychological outcome
after carotid angioplasty: a randomized controlled trial. J Neurol Neu-
rosurg, Psychiatry 1999;66 (Suppl):262.
12. Grunwald IQ, Suppurian T, Politi M, Struffert T, Falkai P, Krick C, et
al. Cognitive changes after carotid artery stenting. Neuroradiology
2006;48:319-23.
13. Moftakhar R, Turk AS, Niemann DB, Hussain S, Rajpal S, Cook T, et
al. Effects of carotid or vertebrobasilar stent placement on cerebral
perfusion and cognition. AJNR Am J Neuroradiol 2005;26:1772-80.
14. Xu G, Liu X, Meyer JS, Yin Q, Zhang R. Cognitive performance after
carotid angioplasty and stenting with brain protection devices. Neurol
Res 2007;29:251-5.
15. Endovascular versus surgical treatment in patients with carotid stenosis
in the Carotid and Vertebral Artery Transluminal Angioplasty Study
(CAVATAS). a randomised trial. Lancet 2001;357:1729-37.
16. Yadav JS, Wholey MH, Kuntz RE, Fayad P, Katzen BT, Mishkel GJ, et
al; Stenting and Angioplasty with Protection in Patients at High Risk for
Endarterectomy Investigators. Protected carotid-artery stenting versus
endarterectomy in high-risk patients. N Engl J Med 2004;351:1493-
501.
17. Brott TG, Hobson RW 2nd, Howard G, Roubin GS, Clark WM,
Brooks W, et al; CREST Investigators. Stenting versus endarterectomy
for treatment of carotid-artery stenosis. N Engl J Med 2010;1:11-23.
18. Lal BK, Brott TG. The Carotid revascularization Endarterectomy vs.
Stenting Trial completes randomization: lessons learned and antici-
pated results. J Vasc Surg 2009;50:1224-31.
19. Zhu L, Fratiglioni L, Guo Z, Aguero-Torres H, Winblad B, Viitanen M,
et al. Association of stroke with dementia, cognitive impairment, and
functional disability in the very old: a population-based study. Stroke
1998, 1998;29:2094-9.
20. Lal BK, Hobson RW 2nd, Tofighi B, Kapadia I, Cuadra S, Jamil Z, et al.
Duplex ultrasound velocity criteria for the stented carotid artery. J Vasc
Surg 2008;47:63-73.
21. Brott T, Adams H Jr, Olinger CP, Marler JR, Barsan WG, Biller J, et al.
Measurements of acute cerebral infarction: a clinical examination scale.
Stroke 1989;20:864-70.
Lal et al 697
22. DeGroote RD, Lynch TG, Jamil Z, Hobson RW 2nd. Carotid resteno-
sis: long-term noninvasive follow-up after carotid endarterectomy.
Stroke 1987;18:1031-6.
23. Hachinski V, Iadecola C, Petersen RC, Breteler MM, Nyenhuis DL,
Black SE, et al. National Institute of Neurological Disorders and
Stroke-Canadian Stroke Network vascular cognitive impairment har-
monization standards. Stroke 2006;37:2220-41.
24. Blumenthal JA, Mahanna EP, Madden DJ, White WD, Croughwell
ND, Newman MF, et al. Methodological issues in the assessment of
neuropsychologic function after cardiac surgery. Ann Thorac Surg
1995;59:1345-50.
25. Ryan CM, Hendrickson R. Evaluating the effects of treatment for
medical disorders: has the value of neuropsychological assessment been
fully realized? Appl Neuropsychol 1998;5:209-19.
26. Murkin JM, Stump DA, Blumenthal JA, McKhann G. Defining dys-
function: group means versus incidence analysis—a statement of con-
sensus. Ann Thorac Surg 1997;64:904-5.
27. Strauss E, Sherman EMS, Spreen O. A Compendium of Neuropsycho-
logical Tests. Administration, Norms, and Commentary. 3rd ed. New
York: Oxford University Press; 2006.
28. Partington JE, Leiter RG. Partington’s pathway test. The Psychological
Serv Center Bulletins 1949;1:9-20.
29. Wechler D. Wechsler Adult Intelligence Scale. 3rd ed. San Antonio,
Texas: The Psychological Corporation; 1997.
30. Spreen O, Benton A. Neurosensory Center Comprehensive Examina-
tion for Aphasia (ed). Victoria, BC: University of Victoria Neuropsy-
chology Laboratory; 1977.
31. Wechler D. Administration and Scoring Manual for the Wechsler
Memory Scale. 3rd ed. San Antonio, TX: H. Brace; 1997.
32. Goodglass H, Kaplan E. Assessment of Aphasia and Related Disorders.
Philadelphia, PA: Lea & Febiger; 1983.
33. Brandt J, Benedict R. The Hopkins Verbal Memory Test-Revised:
Professional Manual. Lutz, FL: Psychological Assessment Resources,
Inc; 2001.
34. Johnston SC, O’Meara ES, Manolio TA, Lefkowitz D, O’Leary DH,
Goldstein S, et al. Cognitive impairment and decline are associated with
carotid artery disease in patients without clinically evident cerebrovas-
cular disease. Ann Intern Med 2004;140:237-47.
35. Hobson RW 2nd, Mackey WC, Ascher E, Murad MH, Calligaro KD,
Comerota AJ, et al; Society for Vascular Surgery. Management of
atherosclerotic carotid artery disease: clinical practice guidelines of the
Society for Vascular Surgery. J Vasc Surg 2008;48:480-6.
36. ABC News. Carotid artery stent procedure makes you smarter. Avail-
able at: http://abcnews.go.com/GMA/Health/story?id⫽1796304&
page⫽1. Accessed: April 2, 2006.
37. Fisher C. Senile dementia-A new explanation of its causation. Arch
Neurol 1951;65:1-7.
38. Sasoh M, Ogasawara K, Kuroda K, Okuguchi T, Terasaki K, Yamadate
K, Ogawa A. Effects of EC-IC bypass surgery on cognitive impairment
in patients with hemodynamic cerebral ischemia. Surg Neurol 2003;59:
455-60; Discussion:460-53.
39. Younkin D, Hungerbuhler JP, O’Connor M, Goldberg H, Burke A,
Kushner M, et al. Superficial temporal-middle cerebral artery anasto-
mosis: effects on vascular, neurologic, and neuropsychological func-
tions. Neurology 1985;35:462-9.
40. Marshall RS, Lazar RM, Pile-Spellman J, Young WL, Duong DH, Joshi
S, Ostapkovich N. Recovery of brain function during induced cerebral
hypoperfusion. Brain 2001;124:1208-17.
41. Schmidt R, Ropele S, Enzinger C, Petrovic K, Smith S, Schmidt H,
et al. White matter lesion progression, brain atrophy, and cognitive
decline: the Austrian stroke prevention study. Ann Neurol 2005;58:
610-6.
42. Vermeer SE, Prins ND, den Heijer T, Hofman A, Koudstaal PJ, Breteler
MM, et al. Silent brain infarcts and the risk of dementia and cognitive
decline. N Engl J Med 2003, 2003;348:1215-22.
43. Craft TKS, Mahoney JH, DeVries AC, Sarter M. Microsphere embo-
lism-induced cortical cholinergic deafferentation and impairments in
attentional performance. Europ J Neuroscien 2005;21:3117-32.
44. Jordan WD Jr, Voellinger DC, Doblar DD, Plyushcheva NP, Fisher
WS, McDowell HA, et al. Microemboli detected by transcranial Dopp-

698 Lal et al
ler monitoring in patients during carotid angioplasty versus carotid
endarterectomy. Cardiovasc Surg 1999;7:33-8.
45. Flach HZ, Ouhlous M, Hendriks JM, Van Sambeek MR, Veenland JF,
Koudstaal PJ, et al. Cerebral ischemia after carotid intervention. J
Endovasc Ther 2004, 2004;11:251-7.
46. Poppert H, Wolf O, Resch M, Theiss W, Schmidt-Thieme T, Graefin
von Einsiedel H, et al. Differences in number, size and location of
intracranial microembolic lesions after surgical versus endovascular
JOURNAL OF VASCULAR SURGERY
September 2011
treatment without protection device of carotid artery stenosis. J Neurol
2004;251:1198.
47. Cosottini M, Michelassi MC, Puglioli M, Lazzarotti G, Orlandi G,
Marconi F, et al. Silent cerebral ischemia detected with diffusion-
weighted imaging in patients treated with protected and unprotected
carotid artery stenting. Stroke 2005;36:2389-93.
Submitted Dec 3, 2010; accepted Mar 21, 2011.