Report of the Substudy Assessing the Impact of

Neurocognitive Function on Quality of Life 5 Years

After Cardiac Surgery
Mark F. Newman, MD; Hilary P. Grocott, FRCPC; Joseph P. Mathew, MD; William D. White, MPH;
Kevin Landolfo, MD; Joseph G. Reves, MD; Daniel T. Laskowitz, MD; Daniel B. Mark, MD;
James A. Blumenthal, PhD; for the Neurologic Outcome Research Group and the Cardiothoracic
Anesthesia Research Endeavors (CARE) Investigators of the Duke Heart Center

Background and Purpose—The importance of perioperative cognitive decline has long been debated. We recently
demonstrated a significant correlation between perioperative cognitive decline and long-term cognitive dysfunction.
Despite this association, some still question the importance of these changes in cognitive function to the quality of life
of patients and their families. The purpose of our investigation was to determine the association between cognitive
dysfunction and long-term quality of life after cardiac surgery.
Methods—After institutional review board approval and patient informed consent, 261 patients undergoing cardiac surgery
with cardiopulmonary bypass were enrolled and followed for 5 years. Cognitive function was measured with a battery
of tests at baseline, discharge, and 6 weeks and 5 years postoperatively. Quality of life was assessed with well-validated,
standardized assessments at the 5-year end point.
Results—Our results demonstrate significant correlations between cognitive function and quality of life in patients after
cardiac surgery. Lower 5-year overall cognitive function scores were associated with lower general health and a less
productive working status. Multivariable logistic and linear regression controlling for age, sex, education, and diabetes
confirmed this strong association in the majority of areas of quality of life.
Conclusions—Five years after cardiac surgery, there is a strong relationship between neurocognitive functioning and
quality of life. This has important social and financial implications for preoperative evaluation and postoperative care
of patients undergoing cardiac surgery. (Stroke. 2001;32:2874-2881.)
Key Words: cardiac surgical procedures 䡲 cognitive disorders 䡲 quality of life

N eurocognitive decline after cardiac surgery is a common

complication occurring in up to three quarters of pa-
tients at hospital discharge and persisting in a third of patients
up to 6 months after surgery.1 However, the importance of
postoperative cognitive decline is still debated.2 Descriptions
such as “subtle,” “transient,” and “subclinical” have been
used to minimize the importance of these changes to clini-
cians, patients, and their families. In a 5-year prospective
study, we found a significant association between cognitive
decline immediately after cardiac surgery and both the
incidence and severity of cognitive dysfunction at 5 years.3
This linkage between perioperative injury and long-term
cognitive function suggests that perioperative dysfunction
may serve either as a marker of brain injury, increased
See Editorial Comment, page 2880
susceptibility to brain injury, decreased reserve capacity, or
inability to recover or tolerate similar injury (plasticity).
Changes in cognitive function have been associated with
reduced quality of life in a number of different disease
processes and perioperative settings.4 – 8 However, despite the
evidence in some patients of poor outcome (eg, increase in
depression, anxiety, cognitive decline),9,10 most studies have
demonstrated that cardiac surgery has beneficial effects on
psychological functioning and quality of life for the majority
of patients.11 Within 6 months after surgery, most patients
report a reduction in depressive and anxiety symptoms.12
Patients also experience marked improvements in physical
(eg, fewer restrictions on activity, decreased fatigue, fewer

Received December 28, 2000; final revision received June 28, 2001; accepted September 5, 2001.
From the Department of Anesthesiology (M.F.N., H.P.G., J.P.M., W.D.W., J.G.R.), Department of Surgery (K.L.), Department of Medicine, Division
of Neurology (D.T.L.), Department of Medicine, Division of Cardiology (D.B.M.), and Department of Psychiatry and Behavioral Sciences (J.A.B.), Duke
University Medical Center, Durham, NC.
A complete list of the participants in the Neurologic Outcome Research Group and the CARE Investigators of the Duke Heart Center appears in
Appendix 1 and Appendix 2.
Reprint requests to Mark F. Newman, MD, Department of Anesthesiology, Box 3094, DUMC, Duke University Medical Center, Durham NC 27710.
E-mail newma005@mc.duke.edu
© 2001 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org

2874
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 Newman et al Neurocognitive Function and Quality of Life After CABG
sleep problems), sexual (eg, decreased pain and worry,
increased desire and energy), social (eg, increased participa-
tion in social activities and hobbies), and work activity (return
to work, increased job performance).12–14 Furthermore, 1 year
after surgery, patients report increased life satisfaction and
improvements in emotional well-being and family life.15
However, these studies have not included detailed serial
psychometric testing to assess the role of cognitive function.
To determine the clinical importance of cognitive dysfunc-
tion after cardiac surgery, we examined these changes in the
context of other aspects of quality of life in patients with
cardiovascular disease undergoing treatment. The purpose of
our investigation was to determine the impact of neurocog-
nitive dysfunction on quality of life after cardiac surgery.
Subjects and Methods
Patient Enrollment
After institutional review board approval and written informed
consent were obtained, 261 patients undergoing elective cardiac
surgery were enrolled in this investigation. Patients with a history of
symptomatic cerebrovascular disease (with residual deficit), psychi-
atric illness, renal disease (serum creatinine concentration ⬎2.0
mg/dL), active liver disease, less than a seventh-grade education, or
an inability to read were excluded from enrollment.
Measurement of Neurocognitive Function
A brief neurocognitive test battery was administered before surgery
(baseline), the day before discharge (approximately 7 days after
coronary artery bypass grafting [CABG]), and at 6 weeks, 6 months,
and 5 years postoperatively (results of neurocognitive outcome were
previously reported).3 Assessments were performed individually by
experienced psychometricians using a well-validated battery that
included the following: (1) The Short Story module of the Randt
Memory Test requires subjects to recall the details of a short story
immediately after it was read to them (immediate) and after a
30-minute delay (delay). Scoring is based on both the “verbatim” and
“gist” of the response on immediate and delayed testing (4 variable
scores).16 (2) The Digit Span subtest of the Wechsler Adult Intelli-
gence Scale–Revised (WAIS-R) requires subjects to repeat a series
of digits that have been orally presented to them both forward and,
in an independent test, in reverse order (2 variable scores).17 (3) The
Benton Revised Visual Retention Test requires subjects to reproduce
from memory a series of geometric shapes after a 10-second
exposure (1 variable score).18 (4) The Digit Symbol subtest of the
WAIS-R is a paper-and-pencil task that requires subjects to repro-
duce, within 90 seconds, as many coded symbols as possible in blank
boxes beneath randomly generated digits according to a coding
scheme for pairing digits with symbols (1 variable score).17 (5) The
Trail-Making Test (Trails B) requires subjects to connect, by
drawing a line, a series of numbers and letters in sequence (ie,
1-A-2-B) as quickly as possible (1 variable score).19
Measurement of Quality of Life
Quality of life instruments were administered individually by a
trained psychometrician who was blinded to the patient’s neurocog-
nitive test results at the 5-year end point. Most of the questionnaires
were self-administered; however, the measures were read to the
patient if he or she was feeling ill or was unable to read. The
following quality of life measures were used:
(1) The Duke Activity Status Index (DASI).20 The DASI is a
12-item scale of functional capacity that has been found to correlate
well with objective measures of maximal exercise capacity. Items
reflect activities of personal care, ambulation, household tasks,
sexual function, and recreational activities. Activities reported to be
done “with no difficulty” receive scores weighted higher for more
taxing activities, which are summed for a quantitative measure of
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2875
functional status (minimum 0, maximum 58.2). A higher weighted
score is better.
(2) The Medical Outcomes Study 36-Item Short Form Health
Survey (SF-36).21,22 The SF-36 was designed to measure general
health status. The results are expressed in terms of 8 subscores and
2 summary scores: the Physical Component Summary (PCS) and the
Mental Component Summary (MCS). SF-36 items and scales are
scored so that a high score indicates a better health state. Summary
scores have been standardized to the US general population (mean
score of 50⫾10) to allow easier norm-based interpretation.
(3) Center for Epidemiological Studies Depression Scale (CES-
D).23 The CES-D is a 20-item self-report measure designed to
measure symptoms of depression. Subjects rate the degree to which
they have experienced a range of symptoms of depression on items
such as “I had crying spells” and “I felt lonely.” Scores range from
0 to 60, with higher scores indicating greater depressive symptoms.
Scores ⬎16 are typically considered indicative of clinically signifi-
cant depression.
(4) Spielberger State and Trait Anxiety Inventory (STAI).24 The
STAI consists of two 20-item scales that measure state (current) and
trait (chronic) anxiety. Representative items include statements such
as “I feel nervous” and “I feel worried.” These items are rated on a
4-point scale of how well they describe the patient’s current or
typical mood from “not at all” to “very much so.” Scores range from
20 to 80, with higher scores indicating greater anxiety.
(5) Mini-Mental State Examination (MMSE).25 This test is de-
signed to grossly assess executive cognitive functioning. It assesses
orientation, memory, calculations, reading and writing capacity,
visuospatial ability, and language. Patients are quantitatively mea-
sured on those functions; a perfect score is 30 points, a score of ⬍25
suggests impairment, and a score of ⬍20 indicates definite
impairment.25,26
(6) Perceived Social Support Scale.27 Twelve items include how
strongly subjects agree there is “a special person who is around when
I am in need” and “my family really tries to help me.” Choices range
from “very strongly disagree” to “very strongly agree.” Items are
summed for a range of 12 to 84, with a high score indicating a better
status.
(7) Working Status. This is a single-item instrument with 9
possible choices: 1, full time; 2, part time; 3, homemaker; 4,
long-term sick leave; 5, short-term sick leave; 6, retired; 7, disabled;
8, unemployed; 9, other.
Patient Management
Anesthetic management with midazolam, fentanyl, isoflurane, and
vecuronium has been previously described.28 The perfusion appara-
tus consisted of a Cobe CML oxygenator (COBE Chem Labs), a
Sarns 7000 max pump (Sarns Inc), and a Pall SP 3840 arterial line
filter (Pall Biomedical Products Co). Nonpulsatile perfusion of 2 to
2.4 L/min per square meter of body surface area was maintained
throughout the study periods. The pump was primed with crystalloid
solution designed to achieve a hematocrit of ⱖ0.18% during extra-
corporeal circulation. Packed red blood cells were added when
necessary to achieve the desired hematocrit. All patients underwent
cardiopulmonary bypass (CPB) through an ascending aortic cannula.
Arterial carbon dioxide tension was maintained throughout CPB at
35 to 40 mm Hg (uncorrected for temperature), and partial pressure
of oxygen (PaO2) was maintained at 150 to 250 mm Hg.
Statistical Methods
All assessment instruments were scored according to the specific
validated algorithms described by the test developers. In particular, the
DASI uses a weighted sum, and the SF-36 uses weights and transfor-
mations to arrive at its 8 scales and 2 summary components.21
To assess neurocognitive decline over time while minimizing the
potential for redundancy in the neurocognitive measures, a factor
analysis with orthogonal rotation was first performed on the 9
individual baseline neurocognitive test scores. This analysis included
scores from the entire baseline population of 261 patients. Factor
analysis was used as a variable reduction technique to reduce the
larger number of correlated scores to a smaller number of uncorre-
2876 Stroke December 2001

TABLE 1. Patient Demographics

Enrolled Lost to Follow-up 5-Year Participants
Characteristic (n⫽261) (n⫽89) (n⫽172)
Age at surgery, mean⫾SD, y 60.9⫾10.6 61.6⫾10.8 60.8⫾10.4
Education, mean⫾SD, y 12.2⫾3.8 13.0⫾3.8 12.1⫾3.8
Sex, % male 74.7 84.4 71.6
Race, % white 91.2 92.2 89.7
CPB time, mean⫾SD, min 111.6⫾34.5 108.5⫾35.3 113.2⫾34.0
LVEF, mean⫾SD, % 51.7⫾11.9 51.2⫾12.8 52.2⫾11.3
History of hypertension, % 51.2 50.0 51.8
ASA class 4 risk, % 57.4 67.1* 52.5
CCS class IV angina, % 43.0 43.1 43.0
Diabetes, type 1 or 2, % 14.0 15.66 13.2
Previous myocardial infarction, % 47.3 57.1* 42.2
Previous symptomatic neurological event, % 7.6 13.3† 4.8
LVEF indicates left ventricular ejection fraction; ASA, American Society of Anesthesiologists; and
CCS, Canadian Classification System.
*P⫽0.03 for the comparison with patients who completed follow-up.
†P⫽0.02 for the comparison with patients who completed follow-up.

lated variables to be used in the final analysis. The factor loadings demonstrate a significant relationship over and above the effects of
(weights) of each test on each factor were used to construct covariables. Because there was no single way to bring together our
comparable domain scores at the 5-year follow-up time periods on multiple assessment of quality of life, we have presented all of the
the basis of patients’ test scores for that time period. In this manner, univariate and multivariate probability values for comparison.
the domains were identified at baseline and remained consistent at
follow-up.3 Results
Factor analysis on 9 baseline neuropsychological test scores Two hundred sixty-one patients initially enrolled in the study
suggests that 4 factors account for 86% of the variance present in our
and underwent baseline neurocognitive testing. Of these, a
test battery at baseline. The 4 factors coherently represent the
cognitive domains of (1) verbal memory and language comprehen- total of 172 patients were available for 5-year follow-up and
sion (short-term and delayed); (2) abstraction and visuospatial completed both neurocognitive functioning and quality of life
orientation; (3) attention, psychomotor processing speed, and con- assessments (reasons for withdrawal of the 89 patients were
centration; and (4) visual memory. previously described).3 The demographics and background
A change score for each of the factors was calculated by clinical information of this patient population are listed in
subtracting baseline factor scores from the follow-up factor scores.
Categorically, a cognitive deficit was defined as a decline of 1 SD or Table 1. Demographic parameters of the entire population
more in performance on any 1 of the 4 domains. To quantify overall (baseline) and those available for 5-year follow-up were
cognitive function and the degree of learning (practice from repeated similar, with exceptions as noted.
exposure to the testing procedures) or cognitive decline across all
domains, a composite cognitive index was calculated as the sum of TABLE 2. Neurocognitive Function Scores at Baseline
the 4 domain scores to yield a single, continuous measure of
and 5 Years
cognitive function. This summary measure, accounting for improve-
ment as well as decline, was used to represent overall cognitive Baseline 5 Years
functioning as the predictor of interest in our models. Test/Score (n⫽261) (n⫽172)*
The association between quality of life and long-term cognitive
dysfunction was investigated univariately with each of the measures Digit Symbol† 38.78⫾13.71 38.00⫾14.94
of quality of life with the use of our continuous measure of overall Benton Revised Visual Retention 5.14⫾2.25 5.02⫾2.17
cognitive function. Continuous quality of life outcome measures
Randt Delayed Gist‡ 5.01⫾2.14 5.63⫾2.31
were tested with Pearson correlation tests and confirmed with
Spearman correlation tests to guard against nonnormal distributions. Randt Delayed Verbatim‡ 6.23⫾3.26 7.30⫾3.51
For analysis, the 6 responses to the “Work Status” item were grouped Randt Immediate Gist‡ 5.73⫾1.83 6.49⫾1.90
into a dichotomous response of “Yes” if work status was full time,
Randt Immediate Verbatim‡ 7.88⫾3.25 9.21⫾3.34
part time, or homemaker, and “No” if work status was reported as
retired, disabled, or unemployed. Logistic regression was then used Digit Span†
to test the effect of cognitive function on the dichotomous working Repeat Forward 5.43⫾2.26 5.30⫾2.19
outcome. Quality of life outcomes that showed a significant univar-
iate relationship with cognitive function at ␣⫽0.05 were subse- Repeat Backward 7.25⫾2.29 7.00⫾2.29
quently tested in multivariable linear or logistic regression models to Trail Making Test (Trails B) 142.24⫾73.56 184.54⫾146.69
account for the possible competing effects of age, sex, years of Composite cognitive index 0.183⫾1.944 ⫺0.133⫾2.321
education, diabetes, and the 2-way interactions of each of these with
cognitive function. In the multivariate models, the best predictive Values are mean⫾SD.
model without cognitive function was developed first, starting with *Number of patients still participating in trial (excludes withdrawals and
all covariables listed and removing nonsignificant terms iteratively patients lost to follow-up and death).
until only significant terms remained. The effect of cognitive †Subtest of WAIS-R.
function was then added to this “best” model to test whether it would ‡Short Story module of Randt Memory Test.

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 Newman et al Neurocognitive Function and Quality of Life After CABG 2877

TABLE 3. Multivariable Adjusted Effects of Total 5-Year Cognitive Function Score (Factor Sum) on Quality
of Life Measures*
Quality of Life Spearman
Score, Correlation Multivariable Total
Quality of Life Outcome Mean⫾SD Coefficient R P† P‡ Covariates§ Model R 2
DASI weighted sum (higher⫽better) 25.5⫾16.8 0.289 0.0002 0.0085 Age, sex, DM 0.298
Cognitive Difficulties Scale (higher⫽worse) 43.7⫾27.1 ⫺0.308 ⬍0.0001 0.0046 Age, sex, DM, education 0.199
SF-36 Standardized PCS 41.0⫾11.3 0.228 0.0038 0.0170 Sex 0.105
Physical Functioning (10 items) 64.6⫾27.4 0.259 0.0009 0.0010 Sex, DM 0.216
Role—Physical (4 items) 61.8⫾40.2 0.173 0.0296 0.0058 Sex, DM 0.089
Pain Index (2 items) 67.6⫾26.7 0.102 0.1961
General Health Perceptions (5 items) 57.0⫾23.0 0.178 0.0231 0.0037 Age, sex 0.081
SF-36 Standardized MCS 52.7⫾10.1 0.024 0.7600 䡠䡠䡠 䡠䡠䡠 䡠䡠䡠
Vitality (4 items) 53.9⫾23.3 0.089 0.2607 䡠䡠䡠 䡠䡠䡠 䡠䡠䡠
Social Functioning (2 items) 80.2⫾25.8 0.057 0.4745 䡠䡠䡠 䡠䡠䡠 䡠䡠䡠
Role–Emotional (3 items) 78.6⫾33.7 0.146 0.0660 䡠䡠䡠 䡠䡠䡠 䡠䡠䡠
Mental Health Index (5 items) 78.4⫾19.0 0.085 0.2825 䡠䡠䡠 䡠䡠䡠 䡠䡠䡠
CES-D: Depression 10.2⫾9.9 ⫺0.254 0.0012 0.0006 Age, sex, DM 0.177
STAI: State Anxiety 33.0⫾11.8 ⫺0.026 0.7401
STAI: Trait Anxiety 35.0⫾11.5 ⫺0.179 0.0231 0.0071 Age, sex, DM, education 0.206
Perceived Social Support Scale 73.8⫾10.4 ⫺0.137 0.0827 䡠䡠䡠 䡠䡠䡠 䡠䡠䡠
MMSE 27.1⫾3.4 0.617 ⬍0.0001 0.0001 Age, sex 0.455
Working Status (32.4%⫽Yes) Odds ratio⫽1.4 ⬍0.0001㛳 0.0060 Age, sex C⫽0.786¶
*All models allowed for potential effects of age in years, sex, years of education, diabetes mellitus (DM), and preoperative left ventricular ejection fraction.
†Correlation with total 5-year cognitive function score.
‡Effect of cognitive function score in multivariable regression. All models were linear regression on continuous outcome measures except for
working status, which was a logistic regression on the binary outcome of working productively (yes, no).
§Covariates remaining significant in the final model.
㛳P-value from logistic regression with 5-year cognitive function score as single predictor (odds ratio for multiple testing⫽1.3).
¶Logistic model C index.

Cognitive Function cognitive impairment status, change in composite cognitive

The mean values for the raw neurocognitive function test battery
and composite cognitive index scores at baseline and at 5-year
follow-up are shown in Table 2. The raw scores represent the
actual obtained scores from the test battery before factor analy-
sis. Seventy-three patients (42.4%) experienced a decline of at
least 1 SD in at least 1 domain of cognitive function at 5 years.
Patients who showed a deficit also declined significantly on
the composite cognitive index (average change⫽⫺0.91;
P⬍0.0001), while patients with no deficit improved significantly
over the 5 years on the composite cognitive index (average
change⫽0.03; P⫽0.006, t test of no change).
Quality of Life Results
Quality of life results for all measures are reported in Table 3.
Patients’ general health and working status self-ratings 5
years after cardiac surgery are illustrated in Figures 1 and 2.
Participants reported their general health status at 5-year
follow-up to be either excellent, very good, good, fair, or poor
(see Figure 1 for distribution). Only 5.2% of patients reported
a poor general health status.
Association of Quality of Life and Working Status
With Cognitive Function
Univariate associations were assessed between dichotomous
cognitive deficit status, baseline composite cognitive index,
index, 5-year composite cognitive index, and the independent
measures of quality of life. In many areas, significant correla-
tions existed between the cognitive indices and the assessments
of quality of life. Univariate associations were demonstrated
between baseline cognitive index, change in cognitive index,
5-year cognitive index, and quality of life assessed at 5 years.
The association between 5-year composite cognitive index and
5-year quality of life was more robust than the association of
quality of life with baseline cognitive function or change in
function. Two of the associations between 5-year cognitive
index and 5-year quality of life are demonstrated graphically in
Figures 1 and 2. Figure 1 demonstrates the correlation between
absolute level of cognitive function and the individual’s percep-
tion of better general health. Figure 2 demonstrates significant
association between composite cognitive function score and the
individual work status 5 years after CABG.
Multivariate Association of Quality of Life With
Cognitive Function
Table 3 demonstrates the multivariable associations of 5-year
cognitive function level (total score), defined by the compos-
ite cognitive index, and the various measures of quality of life
outcome. Significant covariables in the models are listed as
well as the total R2 for the individual models. Substantial

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2878 Stroke December 2001
Figure 1. Patients’ general health self-rating and 5-year cognitive
function score. (The 5-year cognitive function score is the sum of the
4 domain scores, including cognitive decline and learning effects.)
correlation persisted between 5-year cognitive function and
quality of life in the majority of domains assessed. Additional
variables assessed included age, sex, diabetes, left ventricular
ejection fraction, and education. Where multiple cognitive
indices were placed in the model, 5-year cognition eliminated
other cognitive variables.
Discussion
It is well established that cardiac surgery affects neurocogni-
tive functioning. The results from this investigation further
define a consistent and broad-based association between
neurocognitive function and quality of life 5 years after
cardiac surgery, independent of the recognized effects of age,
sex, diabetes, and education.3,29 The results indicate that
patients’ perception of general health correlates directly with
neurocognitive functioning (Figure 1). In addition, patients
with higher cognitive function scores were more likely to be
working productively 5 years after cardiac surgery, indepen-
dent of age. While some studies have investigated the
longitudinal effects of cardiac surgery on neurocognitive
functioning, there are very few studies that have included
neurocognitive functioning and quality of life in this partic-
ular patient population (Table 3).2,3,8,29 –35 The strengths of
Figure 2. Patients’ work status and 5-year cognitive function
score. (The 5-year cognitive function score is the sum of the 4
domain scores, including cognitive decline and learning effects.)
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our methodology include the longitudinal nature of the study
and our ability to maintain follow-up. Our results are unique
because they provide an overall weighted cognitive function
score (factor sum) instead of individual scores from neuro-
cognitive measures. Although these factors limit the direct
comparisons to other studies, they enhance the inferential
integrity of the statistical results.
Cohen et al8 assessed neurocognitive functioning and im-
provement in quality of life at baseline and after 12 weeks of
cardiac rehabilitation. The study included a small subset of
patients who had undergone cardiac surgery. Cohen noted that
cardiac surgery patients performed significantly worse in mea-
sures of neurocognitive function than the other patients under-
going cardiac rehabilitation at baseline. Baseline quality of life
scores of the PCS and MCS of the SF-36 were also found to be
lower than average in all patients but improved after cardiac
rehabilitation and were statistically significant for PCS rather
than MCS measures. He suggested that because neurocognitive
performance was strongly associated with changes in SF-36
scores, cognitive abilities might be an important determinant of
cardiac rehabilitation outcome.8 Such an observation could also
be applied to the current study such that neurocognitive function
could be a determinant of “cardiac surgery outcome.”
Quality of life is important in the assessment of any invasive
surgical procedure, particularly when performed on a patient
population considered by many to have a limited life expect-
ancy. The primary limitation of our study is the lack of baseline
quality-of-life data in order to measure change over time.
Another limitation is loss to follow-up that is inevitable in the
longitudinal study we have accomplished. The lack of baseline
quality of life data limits our ability to compare cognitive change
with quality of life change or to fully understand or compare the
associations with our different cognitive indices and quality of
life. With no well-defined mechanism to compile our multiple
assessments of quality of life, we have presented all of the
multivariate probability values for comparison. We encourage
readers to assess for themselves the possible role of multiple
comparisons in our analysis.
Implications
The association between neurocognitive functioning and
quality of life has considerable financial and social implica-
tions. With older individuals presenting for cardiac surgery in
ever-increasing numbers, cognitive dysfunction must be re-
duced if patients are to be given the same extension in the
quality as well as the quantity of life that can be offered by
undergoing cardiac surgery. These results further emphasize
the need for aggressive strategies to monitor and improve
both the neurocognitive function and quality of life of
patients after cardiac surgery, a practice that is currently
uncommon.8 Assessment of strategies to provide CABG
without cardiopulmonary bypass should be assessed to deter-
mine whether cardiopulmonary bypass produces cognitive
dysfunction and quality of life change. The same attention
must go into improvement in brain protection and quality of
life that has gone into myocardial protection. Methods must
be developed to minimize the adverse affects of CABG on
cognitive function since deterioration in cognitive function
has adverse societal consequences.
 Newman et al Neurocognitive Function and Quality of Life After CABG
Appendix 1
Neurologic Outcome Research Group of the Duke
Heart Center
Director: M. Newman, MD; Co-Director: J. Blumenthal, PhD;
Director of Operations: J. Mathew, MD. Anesthesiology: F. Clem-
ents, MD; N. de Bruijn, MD; K. Grichnik, MD; H. Grocott, MD; S.
Hill, MD; J. Reves, MD; D. Schwinn, MD; M. Stafford Smith, MD;
J. Kirchner, BS; V. Gaver, BA; M. Harris, RN, BSN; J. Hawkins,
RN, BSN; B. Mickley, BS; M. Tirronen, BS; W. White, MPH; B.
Phillips-Bute, PhD. Behavioral Medicine: J. Blumenthal, PhD; M.
Babyak, PhD. Neurology: C. Graffagnino, MD; D. Laskowitz, MD;
A. Saunders, PhD; W. Strittmatter, MD. Surgery: R. Anderson, MD;
T. D’Amico, MD; R. Davis, MD; D. Glower, MD; R. Harpole, MD;
J. Jaggers, MD; R. Jones, MD; K. Landolfo, MD; C. Milano, MD; P.
Smith, MD; W. Wolfe, MD. Cardiology: D. Mark, MD; E. Peterson,
MD; M. Sketch, Jr, MD; R. Califf, MD.
Appendix 2
Cardiothoracic Anesthesia Research Endeavors
(CARE) Investigators of the Duke Heart Center
Director: M. Newman, MD. Anesthesiology: F. Clements, MD; N. de
Bruijn, MD; K. Grichnik, MD; H. Grocott, MD; S. Hill, MD; A.
Hilton, MD; J. Mathew, MD; J. Reves, MD; D. Schwinn, MD; M.
Stafford Smith, MD; I. Weslby, MD; J. Booth, MD.
Acknowledgments
This study was supported in part by National Institutes of Health
(NIH) grant RO1–AG09663, NIH grant 1R01HL54316, Clinical
Research Centers Program, NIH grant MO1-RR-30, and American
Heart Association Grant-in-Aid 95010970.
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2880 Stroke December 2001
Editorial Comment
Cognitive Function and Quality of Life
Cognitive dysfunction after major surgery is not uncommon.
Cognitive dysfunction is not the same as delirium, encepha-
lopathy, or an altered state of consciousness. Rather, it refers
to a condition in which memory and intellectual abilities
seem impaired when the patient appears to have otherwise
recovered from the immediate effects of surgery. It is a major
concern for the patient, family, and physician when a patient
is found not to be intellectually the same on awakening after
surgery as before.
The precise pathophysiological mechanisms for postoper-
ative cognitive decline are unknown, but are probably mul-
tifactorial.1 Elderly patients undergoing major cardiac surgery
(eg, coronary artery bypass grafting [CABG] and thoracic
vascular surgery)2 and noncardiac surgery (eg, orthopedic and
abdominal)3 are at the greatest risk for postoperative cogni-
tive decline. Other individual patient features that increase the
risk of postoperative cognitive dysfunction include previous
cerebrovascular disease, undetected cognitive impairment or
dementia, and cardiovascular risk factors such as hyperten-
sion, diabetes, and peripheral vascular disease.4 Intraopera-
tive risk factors include surgical technique (eg, duration of
cardiopulmonary bypass and duration of aortic cross-
clamping), hypotension, manipulation of the diseased aorta,
and the effects of general anesthesia and hypothermia.
Atherothromboembolic phenomena (microemboli) and hyp-
oxia with watershed area injury secondary to hypoperfusion
are also possible etiological mechanisms.5–7
Cognitive changes may be obvious when there are gross
deficits in learning, memory, attention, or concentration. The
decline can also be subtle, with problems in initiative and
planning. These changes can persist well beyond the imme-
diate postoperative period, when the effects of anesthesia and
analgesia directly affecting cognitive functions have clearly
worn off. Most mental status changes improve but can persist
for months and years.2,8,9
In a recent report, Newman and colleagues8 found the
incidence of cognitive decline after CABG to be 53% at
discharge, 36% at 6 weeks, 24% at 6 months, and 42% at 5
years. Cognitive decline was defined as a drop of 1 or more
standard deviations from baseline scores on tests in at least 1
of 4 domains of cognitive function identified by factor
analysis. Older age, lower level of education, and evidence of
cognitive decline at discharge were found to be significant
predictors of long-term cognitive dysfunction. This suggests
that injury during surgery caused in some way cognitive
deficits 5 years later. In their accompanying editorial, Selnes
and McKhann10 offer alternative explanations including the
possibility that patients who undergo CABG are not cogni-
tively normal because of comorbid cerebrovascular disease.
In the preceding article, Newman and colleagues have
expanded their earlier study to investigate the relationship
between cognitive function and quality of life 5 years after
Downloaded from http://stroke.ahajournals.org/ by guest on June 25, 2016
CABG. Self-perceived health status/quality of life indices are
useful as broad outcome measures of the impact of disease
and interventions,11 and associations have been found be-
tween cognitive function and quality of life.12,13 The study by
Newman et al represents an important addition to this
literature by demonstrating significant correlations between
quality of life and cognitive function 5 years after CABG.
Lower cognitive status was associated with lower perceived
general health and less-productive work status. Unfortu-
nately, however, the conclusions are limited by the lack of
baseline quality of life data, which makes comparisons with
postsurgical values impossible. Without this comparison, it is
not possible to evaluate whether there has been a change in
quality of life after CABG.
In this study, 5-year quality of life measures (16 continuous
variables) were correlated with 5 cognitive indices, including
the baseline cognitive index score (sum of 4 cognitive domain
scores), change in composite cognitive index at 5 years, and
an absolute 5-year cognitive index score. All 3 composite
indices correlated with the 5-year quality of life measures.
The association between the 5-year cognitive index and
quality of life at 5 years was reported to be more robust than
the association of quality of life with baseline cognitive
function or change in function in the univariate analyses.
It is surprising that baseline cognitive status would corre-
late with 5-year quality of life measures. This raises the
possibility that some of the patients did not have normal
cognitive abilities before the surgery. It is also possible that
the correlations represent spuriously significant results given
the number of comparisons made. The latter explanation is
likely because when the multiple cognitive indices were
placed in the multivariate model, only the 5-year cognitive
index was associated with quality of life.
CABG is a common surgical procedure in the United
States. As with other major surgeries, there is a risk of
cognitive changes that can persist for months and years.
Newman and colleagues eloquently demonstrated this in a
recent study.8 The intent of the current study to investigate
quality of life in patients who have undergone CABG is
important and laudable. However, due to the absence of
baseline quality of life data, the conclusion should be limited
to the association of 5-year cognitive status and 5-year quality
of life.
Joan M. Swearer, PhD, Guest Editor
Department of Neurology
University of Massachusetts Medical School
Worcester, Massachusetts
1. Selnes OA, Goldsborough MA, Borowicz LM Jr, Enger C, Quaskey SA,
McKhann GM. Determinants of cognitive change after coronary artery
bypass surgery: a multifactorial problem. Ann Thorac Surg. 1999;67:
1669 –1676.
 Newman et al Neurocognitive Function and Quality of Life After CABG
2. Borowicz LM, Goldsborough MA, Selnes OA, McKhann GM. Neuro-
psychologic change after cardiac surgery: a critical review. J Cardio-
thorac Vasc Anesth. 1996;10:105–112.
3. Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J,
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857– 861.
4. Newman MF, Croughwell ND, Blumenthal JA, Lowry E, White WD,
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Predictors of cognitive decline after cardiac operation. Ann Thorac Surg.
1995;59:1326 –1330.
5. Caplan LR, Hennerici M. Impaired clearance of emboli (washout) is an
important link between hypoperfusion, embolism, and ischemic stroke.
Arch Neurol. 1998;55:1475–1482.
6. Moody DM, Bell MA, Challa VR, Johnston WE, Prough DS. Brain
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7. Williams-Russo P, Sharrock NE, Mattis S, Szatrowski TP, Charlson ME.
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8. Newman MF, Kirchner JL, Phillips-Bute B, Gaver V, Grocott H, Jones RH,
Mark DB, Reves JG, Blumenthal JA; Neurological Outcome Research
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2881
Group and the Cardiothoracic Anesthesiology Research Endeavors Investi-
gators. Longitudinal assessment of neurocognitive function after coronary-
artery bypass surgery. N Engl J Med. 2001;344:395–402.
9. Selnes OA, Royall RM, Grega MA, Borowicz LM Jr, Quaskey S,
McKhann GM. Cognitive changes 5 years after coronary artery bypass
grafting: is there evidence of late decline? Arch Neurol. 2001; 58:
598 – 604.
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N Engl J Med. 2001;344:451– 452.
11. Rumsfeld JS, MaWhinney S, McCarthy M Jr, Shroyer AL, VillaNueva
CB, O’Brien M, Moritz TE, Henderson WG, Grover FL, Sethi GK,
Hammermeister KE; participants of the Department of Veterans Affairs
Cooperative Study Group on Processes, Structures, and Outcomes of Care
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tality following coronary artery bypass graft surgery. JAMA. 1999;281:
1298 –1303.
12. Cohen RA, Moser DJ, Clark MM, Aloia MS, Cargill BR, Stefanik S,
Albrecht A, Tilkemeier P, Forman DE. Neurocognitive functioning and
improvement in quality of life following participation in cardiac rehabil-
itation. Am J Cardiol. 1999;83:1374 –1378.
13. Lloyd AJ, Boyle J, Bell PRF, Thompson MM. Comparison of cognitive
function and quality of life after endovascular or conventional aortic
aneurysm repair. Br J Surg. 2000;87:443– 447.
Report of the Substudy Assessing the Impact of Neurocognitive Function on Quality of Life
5 Years After Cardiac Surgery
Mark F. Newman, Hilary P. Grocott, Joseph P. Mathew, William D. White, Kevin Landolfo,
Joseph G. Reves, Daniel T. Laskowitz, Daniel B. Mark and James A. Blumenthal
for the Neurologic Outcome Research Group and the Cardiothoracic Anesthesia Research
Endeavors (CARE) Investigators of the Duke Heart Center

Stroke. 2001;32:2874-2881
doi: 10.1161/hs1201.099803
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