Neurologic Critical Care

Six-month neuropsychological outcome of medical intensive care

unit patients
James C. Jackson, PsyD; Robert P. Hart, PhD; Sharon M. Gordon, PsyD; Ayumi Shintani, PhD;
Brenda Truman, MSN; Lisa May, BSN; E. Wesley Ely, MD, MPH

Objective: To examine neuropsychological function, depres-
sion, and quality of life 6 months after discharge in patients who
received mechanical ventilation in the intensive care unit.
Design: Prospective cohort study.
Setting: Tertiary care, medical and coronary intensive care unit
of a university-based medical center.
Study Population: A total of 275 consecutive, mechanically
ventilated patients from a medical intensive care unit were pro-
spectively followed. At 6 months, 157 were alive, of whom 41
(26%) returned for extensive follow-up testing.
Measurement and Main Results: Neuropsychological testing
and assessment of depression and quality of life were performed
at 6-month follow-up. Seven of 41 patients were excluded from
further analysis due to preexisting cognitive impairment deter-
mined via surrogate interviews using the Modified Blessed De-
mentia Rating Scale and a review of medical records. On the basis
of strict criteria derived from normative data, we found that 11 of
34 patients (32%) were neuropsychologically impaired. Impair-
ment was generally diffuse but occurred primarily in areas of
psychomotor speed, visual and working memory, verbal fluency,
and visuo-construction. The rate of neuropsychological deficits in
the study population was markedly higher than population norms
for mild dementia. Scores on the Geriatric Depression Scale–Short
Form were significantly more abnormal in the neuropsychologi-
cally impaired group than in the nonimpaired group at hospital
discharge (p ⴝ .04) and at 6-month follow-up (p ⴝ .02), and
clinically significant depression was found in 27% of impaired
subjects at hospital discharge and in 36% at 6-month follow-up.
No differences were observed between groups in quality of life as
measured with the Short Form Health Survey-12 at discharge or
6-month follow-up.
Conclusions: Prolonged neuropsychological impairment is
common among survivors of the medical intensive care unit and
occurs with greater than anticipated frequency when compared
with relevant normative data. Future investigations are warranted
to elucidate the nature of the association between critical illness,
neuropsychological impairment, depression, and decreased qual-
ity of life. (Crit Care Med 2003; 31:1226 –1234)
KEY WORDS: cognitive impairment; critical illness; delirium; de-
pression; encephalopathy; mechanical ventilation; neuropsycho-
logical assessment; psychoactive medications; quality of life;
respiratory disease

R apid technological and medi-
cal advances have combined
to facilitate the treatment of
critically ill patients. Indeed,
many patients recover from critical ill-
ness they may not have survived a decade
ago (1–5). Those who survive often fail to
return to baseline levels of health and
report diminished quality of life (6 – 8). In
addition, the psychiatric consequences of
critical illness are being studied with
heightened scrutiny (9 –13).
In the last decade, researchers have
become increasingly interested in the re-
From the Department of Internal Medicine, Divi-
sions of General Internal Medicine and Center for
Health Services Research and the Geriatric Research
Education and Clinical Center of the Veterans Admin-
istration Tennessee Valley Healthcare System, Nash-
ville, TN (JCJ, SMG, AS, BT, LM, EWE); the Division of
Allergy/Pulmonary/Critical Care Medicine, Vanderbilt
University School of Medicine, Nashville, TN (EWE); the
Department of Psychiatry, Vanderbilt University School
of Medicine (SMG); and the Department of Psychiatry,
lationship between critical illness and
cognitive outcomes, and a small but im-
pressive body of evidence is emerging
that documents pervasive neuropsycho-
logical impairment among patients after
critical illness (14). Among patients with
sepsis, encephalopathy has been reported
to occur acutely in as many as 70% of
cases (15, 16), and diffuse neuropsycho-
logical deficits have been documented in
individuals with toxic shock syndrome (17),
yet few data exist regarding the long-term
neuropsychological consequences of sepsis.
In the acute respiratory distress syndrome,
Virginia Commonwealth University Health Systems,
Richmond, VA (RPH).
Dr. Ely was supported, in part, by the AFAR Phar-
macology in Aging Grant, the Paul Beeson Faculty
Scholar Award from the Alliance for Aging Research,
and a K23 from the National Institutes of Health
(AG01023-01A1).
Copyright © 2003 by Lippincott Williams & Wilkins
DOI: 10.1097/01.CCM.0000059996.30263.94
80% of survivors in one cohort were found
to have impaired memory, attention, con-
centration, or decreased processing speed a
year after hospital discharge (18), and in
another report, nearly 25% had mild cog-
nitive impairment even 6 yrs after their
intensive care unit (ICU) stay (19). How-
ever, there are no prospective reports de-
scribing neuropsychological impairment in
the general medical ICU population. In ad-
dition, no information is currently available
on the prognostic significance of delirium
during an ICU stay in regard to long-term
neuropsychological outcome. The few data
that exist for general medical patients in
studies that take into account preexisting
cognitive impairment suggest that long-
term mental status is worse in patients
with a history of delirium (20 –22).
We therefore undertook the current
investigation to study the prevalence and
types of neuropsychological impairment
among medical ICU patients who had de-
veloped respiratory failure necessitating

1226 Crit Care Med 2003 Vol. 31, No. 4

mechanical ventilation from a variety of
etiologies. Using well-validated surrogate
instruments, we were careful to exclude
patients with any detectable baseline neu-
ropsychological impairment, and we
chose strict thresholds for categorizing
patients as impaired at a point in time
considerably remote from their ICU stay
(i.e., 6-month examinations after hospital
discharge).
MATERIALS AND METHODS
Subjects. All patients admitted to the med-
ical and coronary ICUs at the Vanderbilt Uni-
versity Medical Center between the dates of
February 21, 2000, and May 3, 2001, who were
treated with mechanical ventilation were as-
sessed for enrollment in the study by two
research nurses. Patients with mental retarda-
tion, brain lesions, neurologic disorders affect-
ing cognitive function, or major psychiatric
illness were excluded, as were those unable to
communicate with examiners because of sen-
sory deficits or limitations in the use of En-
glish. Of the 275 patients in the study popu-
lation, 96 (34%) died while in the hospital, and
an additional 23 (8%) died within 6 months of
hospital discharge. Of the remaining 157 pa-
tients, 27 (17%) were either too ill to partici-
pate in follow-up assessment or declined par-
ticipation, and 89 (57%) were lost to follow-
up, despite multiple methods and attempts to
contact or find them. Because Vanderbilt Med-
ical Center is a major tertiary care facility,
study participants were frequently from other
states and, in many cases, did not live within
easily drivable distances. A total of 41 (26%)
Table 1. Test descriptions
Test Author/Year (Reference No.)
APACHE II Knaus et al., 1985 (24)
Brussels Bernard 1997 (25)
CAM-ICU Ely et al., 2001 (28, 29)
GCS Teasdale and Jennett, 1974 (30)
GDS-SF Sheikh & Yesavage, 1986 (33)
mBDRS Kay, 1977 (23)
MMSE Folstein et al., 1975 (35)
RASS Sessler et al., 2002 (31)
SOFA Vincent et al., 1996 (26)
SF-12 Ware et al., 1996 (34)
APACHE II, Acute Physiology and Chronic Health Evaluation II; Brussels, Brussels Organ Failure Assessment; CAM-ICU, Confusion Assessment Method
for the Intensive Care Unit; GCS, Glasgow Coma Scale; GDS-SF, Geriatric Depression Scale–Short Form; mBDRS, modified Blessed Dementia Rating Scale;
MMSE, Mini Mental State Exam; RASS, Richmond Agitation and Sedation Scale; SOFA, Sequential-related Organ Failure Assessment; SF-12 ⫽ Short Form
Health Survey-12.
Crit Care Med 2003 Vol. 31, No. 4
returned to receive a formal neuropsycholog-
ical evaluation 6 months after hospital dis-
charge. Screening for preexisting cognitive
impairment had taken place at the time of
enrollment through surrogate interviews that
included the Modified Blessed Dementia Rat-
ing Scale (mBDRS) (23). Patients were defined
as having suspected dementia if their mBDRS
score was ⱖ3 or if they had a history of de-
mentia based on review of medical records and
other available information. A cutoff of 3 was
used for the mBDRS, rather than the recom-
mended cutoff of 4, to provide more sensitive
criteria to detect suspected preexisting de-
mentia. It was determined a priori that pa-
tients who met this criterion would be ex-
cluded from further analysis. The Vanderbilt
University Institutional Review Board ap-
proved this study, and informed consent was
obtained from patients or their surrogates at
the time of enrollment.
Procedures. In addition to the mBDRS,
enrollment data included the Acute Physiol-
ogy and Chronic Health Evaluation II
(APACHE II) (24), Brussels Organ Failure As-
sessment (25), and the Sequential-Related Or-
gan Failure Assessment(26, 27). Patients were
assessed daily with the Confusion Assessment
Method for the ICU for delirium (28, 29), Glas-
gow Coma Scale (30), and the Richmond Ag-
itation Sedation Scale (31, 32). At hospital
discharge, patients were assessed with the Ge-
riatric Depression Scale–Short Form (GDS-
SF) (33); Short Form Health Survey (34),
which includes the Mental Component Sum-
mary or Physical Component Summary; and
the Mini-Mental State Exam (MMSE) (35) (Ta-
ble 1).
Description
A severity of illness scoring system
A scoring system that grades organ dysfunction
A 2-min assessment tool to detect delirium in
mechanically ventilated patients
A 15-point scale measuring pupillary, verbal, and
motor responses
A 15-point screening tool designed to measure
depression among geriatric populations
A 17-point surrogate instrument to screen for
dementia
A brief 30-point tool assessing mental status
A 10-point scale (⫹5 to ⫺5) used to rate
agitation and sedation
A scoring system (0–4) that provides a severity of
illness score
A 12-point generic quality of life measure
Neuropsychological Battery and Criteria
for Impairment. A battery of neuropsycholog-
ical tests was designed specifically to assess
function in ICU survivors by two of the inves-
tigators (R. P. Hart, S. M. Gordon) and admin-
istered 6 months (⫾1 month) after hospital
discharge by a neuropsychologist (S. M. Gordon)
or a clinical psychologist (J. C. Jackson) pro-
ficient and experienced in neuropsychological
assessment or by a trained research nurse (B.
Truman, L. May). At that time, patients were
also assessed with the GDS-SF and Short
Form Health Survey. The neuropsychological
battery contained standardized, well-validated
tests surveying core areas of neuropsycholog-
ical functioning (Table 2) and took approxi-
mately 1–1.5 hrs to administer. The MMSE is
a formalized brief screening instrument that
tests a restricted set of cognitive functions and
provides a gross estimate of mental ability
(35). Digit Symbol Coding is a test of psy-
chomotor speed that tests a subject’s ability to
fill in a series of blanks using a key containing
numbers and nonsense symbols (36). The
Thurstone Word Fluency Test is designed to
measure verbal fluency and the speed and flex-
ibility of verbal thought processes (37). Letter-
Number Sequencing is a test of working mem-
ory involving the correct ordering of letters
and numbers (36). Verbal Paired Associates is
a paired word-learning test that measures ver-
bal memory (36). Faces is a recognition test
that measures immediate and delayed visual
memory (38). Digit Symbol Paired Recall is a
test of visual memory involving the recall of
pairs of symbols and numbers (36). The Rey
Osterrieth Complex Figure is a drawing test
consisting of both copying and delayed com-
ponents that assesses visuo-construction and
Area Measured
Global measure of severity of illness
Measure of organ dysfunction in six different
systems
A measure of delirium
Global measure of cognitive status
Global measure of depression
Gross measure of dementia and cognitive
impairment
Global measure of a restricted set of cognitive
functions
Measure of the presence and/or degree of
agitation/sedation
Describes a sequence of complications in the
critically ill
Global measure of physical and mental quality
of life
1227
Table 2. Neuropsychologic test descriptions

Test Author/Year (Reference No.) Items Total Points Area Measured

Digit Symbol Coding Wechsler, 1997 (36) 133 133 Psychomotor speed
Thurstone Word Fluency Thurstone and Thurstone, 1962 (37) Unlimited 1 point per word Verbal Fluency
Letter Number Sequencing Wechsler, 1997 (36) 21 21 Working Memory
Sequencing
Verbal Paired Associates Wechsler, 1997 (36) Verbal Memory
Immediate 32 32
Delayed 8 8
Digit Symbol Paired Recall Wechsler, 1997 (36) 18 18 Visual Memory
Recall
Faces Wechsler, 1997 (38) Visual Memory
Immediate 24 24
Delayed 48 48
Rey Osterrieth Complex Figure Rey, 1958 (39)
Figure
Copy 36 Visuo-construction
30 Minute Recall 36 Visual Memory

Digit Symbol Coding, Letter Number Sequencing, Verbal Paired Associates, and Digit Symbol Paired Recall are from the WAIS-III (Wechsler Adult
Intelligence Scale Battery). Thurstone Word Fluency requires a subject to list as many words as possible beginning with the letters S and C during two
timed intervals (5 mins and 4 mins). Verbal Paired Associates Immediate consists of four 8-point subscales. The REY Osterrieth Complex Figure requires
a subject to copy a complex geometric figure and to reproduce it from memory after a 30-min delay.

perceptual organization and visual memory
(39). For a more comprehensive description of
these tests, which together comprise the neu-
ropsychological battery, refer to Lezak (40).
As previously detailed, this battery was de-
signed to assess seven cognitive domains:
mental status, psychomotor speed, verbal flu-
ency, working memory, verbal memory, visual
memory, and visuo-construction. Each patient
was classified as impaired or nonimpaired on
the basis of normative population data. Pa-
tients were considered impaired if they had
either two neuropsychological test scores that
were at least 2 SD below the norm-referenced
mean or three scores that were at least 1.5 SD
below the norm-referenced mean. These cri-
teria for impairment were determined using
published methodology according to the num-
ber of tests in the battery, which minimized
the probability that an individual could exceed
the cutoff for impairment by chance at the
␣-level of significance of .05 (41). For the
purposes of this report, patients who had ab-
normal neuropsychological test results but
who did not meet the above stringent criteria
were classified as nonimpaired.
Data Management and Statistical Analy-
sis. Descriptive analyses on these data were
performed, and mean scores and standard de-
viations were obtained. On Letter-Number Se-
quencing, Digit Symbol Coding, Verbal Paired
Associates, and Faces, age-corrected scaled
scores were obtained from the Wechsler Adult
Intelligence Scale–Third Edition (36) or
Wechsler Memory Scale–Third Edition (38),
and for Digit Symbol Pair Recall, age-
corrected percentiles were converted to T-
scores. For Verbal Paired Associates and Faces,
the averages of age-corrected scaled scores for
immediate and delayed trials were used. For
the Rey Osterrieth Complex Figure, age norms
from Spreen and Strauss (42) were used to
obtain Z-scores. For the Thurstone Word Flu-
ency Test, T-scores adjusted for age, educa-
tion, and sex were obtained from the Heaton et
al. (43) manual. For the MMSE, Z-scores were
derived from the age- and education-adjusted
norms of Crum et al (44). All scores were later
converted to T-scores for consistency of pre-
sentation. Comparisons of baseline character-
istics between the impaired and nonimpaired
patients and comparisons of neuropsycholog-
ical test scores were performed using Wilcox-
on’s rank-sum tests, as were comparisons of
follow-up and nonfollow-up patients. Compar-
isons of GDS-SF, Short Form Health Survey,
and MMSE scores at discharge and 6-month
follow-up and the degree of change occurring
between hospital discharge and 6-month fol-
low-up between impaired and nonimpaired pa-
tients were also made using Wilcoxon’s rank-
sum tests. SAS 8.12 (Cary, NC) was used for all
statistical analysis. An alpha of .05 was used to
indicate significance for all analyses.
RESULTS
Patient Baseline Characteristics. The
present study focused on a population
composed of 41 patients. Of these, seven
were determined to have preexisting cog-
nitive impairment and were therefore ex-
cluded from our final analysis and im-
pairment characterization, leaving a final
sample size of 34. To ensure that our final
sample was representative, we compared
baseline demographic and other data ob-
tained at the time of hospital discharge
between our final sample and the 146
patients not receiving follow-up testing
(Table 3). No significant differences were
found between groups with regard to age
(54.2 vs. 53.2 yrs, p ⫽ .58) or severity of
illness as measured by APACHE II (24.9
vs. 24.9, p ⫽ .92). Significant differences
existed between groups on measures of
depression and mental status at the time
of hospital discharge. The mean GDS-SF
score was significantly lower for the pa-
tients not receiving follow-up testing
than for the follow-up group (2.5 vs. 4.5,
p ⫽ .0004). Similarly, the mean MMSE
score was significantly lower for nonfol-
low-up than for follow-up patients (20.4
vs. 24.4, p ⫽ .01).
For purposes of comparison, the final
population was divided into two groups—
impaired (n ⫽ 11) and nonimpaired (n ⫽
23)— using criteria defined a priori
(“METHODS”). The baseline demograph-
ics of the patients are shown in Table 4.
The mean age of the impaired group was
60.3 ⫾ 16.2 yrs and, for the nonimpaired
group, was 49.2 ⫾ 13.5 yrs (p ⫽ .07),
with four patients 65 yrs or older in each
respective group. The mean years of ed-
ucation were significantly lower among
the impaired than among the nonim-
paired group (11.3 vs. 14.1 yrs, p ⫽ .03).
This cohort was found to have a high
severity of illness and a broad range of
causes of respiratory failure, with no sig-
nificant differences between the two
groups (p ⬎ .20 for all) in any of the three
measures of severity presented in Table 4.
Hospital Outcomes (Length of Stay
and Disposition). The duration of me-
chanical ventilation was similar between
the impaired and nonimpaired patients
(median, 6 days [interquartile ranges,
4 –12 for impaired] vs. 7 days [4 to 11], p
⫽ .94). The length of stay in the ICU for
impaired vs. nonimpaired patients was 10

1228 Crit Care Med 2003 Vol. 31, No. 4

Table 3. Comparison of nonfollow-up patients and follow-up patients For the 23 nonimpaired patients, 14
(60.9%) went home and nine (39.1%)
Outcome Nonfollow-up Follow-up
went to another healthcare facility (one
Variable (n ⫽ 146) (n ⫽ 34) p Value
to a nursing home, six to a subacute
Age, yrs 54.2 (17.4) 53.2 (15.3) 0.58 facility, two to another hospital).
Race, Black 33 (22.6%) 7 (21%) 0.80 Neuropsychological Data. Of the 34
Sex, female 73 (50%) 16 (47%) 0.76 patients without apparent preexisting
ADL 0.9 (2.2) 0.6 (1.9) 0.22 cognitive impairment, 11 (32%) were
APACHE 24.9 (8.3) 24.9 (8.8) 0.92
Charlson 3.3 (2.8) 3.8 (3.0) 0.39
classified as impaired at 6-month fol-
GDS-SF 2.5 (3.3) 4.5 (3.3) 0.0004 low-up using our strict criteria. Differ-
mBDRS 0.3 (0.9) 0.04 (0.1) 0.15 ences in age and level of education were
MMSE 20.4 (8.8) 24.4 (6.4) 0.01 noted between groups, although the nor-
PCS 12 33.1 (9.3) 33.6 (8.7) 0.81 mative data we employed adjusted either
MCS 12 45.5 (12.2) 43.9 (10.1) 0.40
for age or for age and education (“METH-
ADL, activities of daily living; APACHE, Acute Physiology an Chronic Health Evaluation; GDS-SF, ODS”). The mean raw test scores for the
Geriatric Depression Scale–Short Form; mBDRS, modified Blessed Dementia Rating Scale; MMSE, impaired and nonimpaired patients are
Mini-Mental State Exam; PCS, Physical Component Summary; MCS, Mental Component Summary. presented in Table 5, and the mean T-
All data presented as mean (⫾SD); higher scores on the GDS-SF are more positive (e.g., reflect scores are presented by domain in Figure
greater levels of depression); lower scores on both the MMSE and the MCS12 and PCS12 are more 1. Scores for Faces and Verbal Paired As-
negative (e.g., reflect lower levels of mental status and lower levels of quality of life, respectively). sociates are presented separately for im-
mediate and delayed trials. All 11 im-
paired patients (100%) demonstrated
Table 4. Patient Baseline Characteristics
memory impairment on at least one mea-
Impaired Nonimpaired sure, five (45%) demonstrated memory
Characteristic (n ⫽ 11) (n ⫽ 23) p Value impairment on at least two measures,
and four (36%) on three or more mea-
Age, mean (SD) 60.3 (16.2) 49.2 (13.5) .08 sures.
Male, n(%) 5 (45) 13 (56) .57 For the impaired group, abnormalities
Race: White, % 73 83 .53
Black, % 27 17 were pervasive in a few select areas. Nine
Education, mean (SD) 11.3 (5.7) 14.1 (3.4) .03 patients (81%) were impaired on Digit
mBDRS, mean (SD) 0.13 (0.2) 0 .04 Symbol Coding and eight (72%) on recall
Severity of Illness, mean (SD) of Digit Symbol Paired Recall. Impair-
APACHE II 23.5 (6.3) 25.5 (9.8) .57
ment was also widespread (70%, n ⫽ 7)
Brussels 2.1 (0.9) 2.5 (1.3) .42
SOFA 10.0 (2.6) 10.3 (3.6) .78 on the Thurstone Word Fluency and on
Organ Involvement (SOFA), mean (SD) the Rey Osterrieth Complex Figure (63%
Cardiovascular 1.4 (1.3) 1.6 (1.4) .81 on both the copy and the recall trial, n ⫽
Coagulation 0.6 (1.1) 0.9 (1.2) .48 6) (Fig. 2 shows patient examples of the
Central nervous system 2.8 (1.2) 2.7 (1.6) .85
Liver 1.2 (1.0) 1.4 (0.9) .48 Rey Osterrieth Complex Figure copy). At
Renal 0.9 (1.4) 1.2 (1.4) .50 least one patient was impaired on every
Respiratory 3.0 (1.2) 2.4 (1.0) .12 remaining test. Although nonimpaired
Admission Diagnoses, n (%) subjects failed to meet our predetermined
Cardiovascular 0 3 (13.0) .53
criteria for a designation of impairment,
Gastrointestinal 1 (9.1) 0 .32
Hematology/Oncology 0 3 (13.0) .53 in some instances, they also displayed
Neurologic 2 (18.2) 1 (4.4) .24 neuropsychological deficits. These defi-
Perioperative Managment 0 1 (4.4) 1.00 cits occurred most frequently on Digit
Pulmonary 7 (63.6) 14 (60.9) 1.00 Symbol Coding (26%, n ⫽ 6) and Word
Renal/metabolic 1 (9.1) 1 (4.4) 1.00
Fluency (17%, n ⫽ 4).
APACHE II, Acute Physiology and Chronic Health Evaluation II; Brussels, Brussels Organ Failure Age and Education Adjustment.
Assessment; mBDRS, Modified Blessed Dementia Rating Scale; SOFA, Sequential Organ Failure Spearman’s correlation coefficients for
Assessment. age, education, and mBDRS against each
Secondary diagnoses for both impaired and nonimpaired groups included: cardiac (11.8%), T-score in the neuropsychological battery
hematology/oncology (2.9%), neurologic (2.9%), pulmonary (14.7%), and renal/metabolic (8.8). A suggested a trend toward a statistical as-
total of 58.8% of patients did not have a secondary diagnosis, and there were no significant differences sociation between age (p ⫽ .08) and im-
between the groups. pairment and significant associations for
education (p ⫽ .034) and mBDRS (p ⫽
.035). We therefore employed multivari-
days (8 –13 days) vs. 10 days (6 –15 days), tween groups (p ⫽ .61). For the 11 im- ate analysis of variance, regressing a set
p ⫽ .77. The length of stay in the hospital paired patients, five (45.6%) went home, of the nine T-scores on patient’s impair-
for impaired vs. nonimpaired patients five (45.6%) went to another healthcare ment status, controlling for age, educa-
was 18 days (14 –24 days) vs. 24 days facility (one to a nursing home, three to a tion, and mBDRS. The p value based on
(17–32 days), p ⫽ .35. Discharge disposi- subacute facility, one to another hospi- Wilks’ Lambda for impaired vs. nonim-
tion was not significantly different be- tal), and one patient’s data were missing. paired after adjusting for these baseline

Crit Care Med 2003 Vol. 31, No. 4 1229

Table 5. Neuropsychologic test scores at 6-mo follow-up earning scores of ⱖ6. There were no sig-
nificant differences in the degree of
Impaired Non-impaired
change occurring in GDS-SF scores
Domain Measure (n ⫽ 11) (n ⫽ 23)
(⫺0.2 vs. 0.5, p ⫽ .76) between impaired
Mental status Mini-Mental State Exam 24.6 (4.4) 28.8 (1.2) and nonimpaired patients over 6 months.
Psychomotor speed Digit Symbol Coding 30.3 (17.1) 57.6 (21.1) Quality of Life. No significant differ-
Verbal fluency Thurstone Word Fluency 22.2 (16.8) 47.5 (14.4) ences in quality-of-life scores (Short
Working memory Letter Number Sequencing 6.0 (2.5) 10.3 (2.1) Form Health Survey) were observed be-
Verbal memory Verbal Paired Associates:
Immediate 9.2 (6.9) 17.8 (7.1)
tween groups at the time of hospital dis-
Delay 3.0 (2.3) 5.8 (2.1) charge on either Mental Component
Visual memory Digit Symbol Pair Recall Faces 2.9 (3.0) 12.2 (4.6) Summary (43.6 vs. 44.1, p ⫽ .88) or
Faces Physical Component Summary (32.8 vs.
Immediate 34.9 (7.1) 34.8 (4.4) 34.0, p ⫽ .81). Similarly, there were no
Delay 34.9 (6.2) 36.9 (5.7)
REY-O Recall 4.2 (5.5) 14.2 (6.4) significant differences between impaired
Visuo-construction REY-O Copy 19.4 (9.9) 32.3 (4.1) and nonimpaired groups at 6-month fol-
low-up on either the Mental Component
All data presented as mean (⫾ SD); higher scores reflect greater levels of performance. Summary (45.0 vs. 51.5, p ⫽ .15) or the
Physical Component Summary (32.7 vs.
39.5, p ⫽ .20) (Table 6). Finally, there
were no significant differences in the de-
gree of change occurring in Mental Com-
ponent Summary (⫺1.4 vs. ⫺8.1, p ⫽
.33) or Physical Component Summary
(0.02 vs. ⫺6.2, p ⫽ .23) scores between
impaired and nonimpaired patients over
6 months.

DISCUSSION
This study demonstrates that in a gen-
eral medical ICU cohort, neuropsycho-
logical impairment is common among
mechanically ventilated patients after
hospital discharge. Using conservative
criteria to define impairment, we found
that nearly one third of patients were
impaired on neuropsychological testing
at 6-month follow-up. Furthermore, we
found that the mean MMSE score at hos-
Figure 1. Histogram plotting the mean T-scores of the impaired and nonimpaired groups according to pital discharge among patients not par-
the primary domains of the neuropsychological functioning tested. T-scores represent a mean of 50 ticipating in follow-up was both below
and a SD of 10. The visual memory score is the average of Faces I and II, Digit Symbol Pair Recall, and the commonly recognized impairment
Rey Osterrieth Complex Figure Recall. Mean composite T-scores are 35.4 (impaired) and 49.3 cutoff of 24 and significantly lower than
(nonimpaired). the mean score of our final sample. This
suggests that cognitive impairment is
likely more pervasive among survivors of
covariates was .0005 (i.e., a highly signif- ⫺2.2, p ⫽ .44), as were mean scores on critical illness than our estimate reflects.
icant difference between groups as cate- the Glasgow Coma Scale (9.7 vs. 10.5, p In addition, as shown by other investiga-
gorized). In other words, our categoriza- ⫽ .48). tions (8, 13, 45), this study also con-
tion scheme for impairment was Depression. At hospital discharge, the firmed that diminished quality of life and
maintained. mean score of the impaired group on the depression were experienced by survivors
Delirium and Sedation Scale Mea- GDS-SF was significantly higher (i.e., of mechanical ventilation after their ICU
surements. During the ICU stay, duration more abnormal) than the mean score of stay.
of delirium (as measured by the Confu- the nonimpaired group (6.2 vs. 3.7, p ⫽ Abnormalities found in our impaired
sion Assessment Method for the ICU) was .04) (Table 6), and 27% and 8% of pa- sample were commensurate with clinical
slightly greater for the impaired than for tients met criteria for clinically signifi- dementia of at least mild severity and
the nonimpaired group (4.5 vs. 4.2 days, p cant depression (ⱖ6) in the impaired and were most striking in specific neuropsy-
⫽ .24). Over the duration of the ICU stay, nonimpaired groups, respectively. At chological domains. For example, impair-
sedation scale scores (i.e., Richmond Ag- 6-month follow-up, group means were ment in visuo-construction was particu-
itation Sedation Scale) were lower (al- again significantly different (6.4 vs. 3.0, p larly severe, as was impairment in other
though not significantly so) for impaired ⫽ .02), with four impaired patients (36%) domains such as visual memory, psy-
than nonimpaired subjects (⫺2.6 vs. and four nonimpaired patients (17%) chomotor speed, and verbal fluency. Us-

1230 Crit Care Med 2003 Vol. 31, No. 4

Figure 2. Rey Osterrieth Complex Figure, a test of visuo-construction in which the patient is asked to copy a complex geometric design, was administered
to all patients 6 months after hospital discharge as a component of the neuropsychological battery. This Figure shows the original Rey Osterrieth Complex
Figure and the examples of three patients (all of whom had no detectable baseline cognitive deficits) as a visual depiction of the character of deficits found
in the study cohort. ARDS, acute respiratory distress syndrome. Reproduced by special pernission of the Publisher, Psychological Assessment Resources,
Inc., 16204 North Florida Avenue, Lutz, FL 33549, from the Rey Complex Figure Test and Recognition Trial by John E. Meyers, Kelly R. Meyers. Copyright
1992 by PAR, Inc. Further reproduction is prohibited without permission of PAR, Inc.

Table 6. Depression and quality-of-life indices

Hospital Discharge 6-Mon Follow-up

Impaired Nonimpaired Impaired Nonimpaired

Instrument (n ⫽ 11) (n ⫽ 23) p Value (n ⫽ 11) (n ⫽ 23) p Value

GDS-SF 6.2 (3.1) 3.7 (3.1) .04 6.4 (4.3) 3.0 (3.4) .02
MCS-12 43.6 (12.1) 44.1 (9.0) .88 45.0 (11.6) 51.5 (11.0) .15
PCS-12 32.8 (8.9) 34.0 (8.8) .81 32.7 (11.9) 39.5 (12.6) .20

GDS-SF, Geriatric Depression Scale–Short Form; MCS, Mental Component Summary; PCS, Physical Component Summary.
All data presented as mean (⫾SD); higher scores on the GDS-SF reflect greater levels of depression; higher scores on both the MCS-2 and PCS-12 reflect
more favorable ratings of quality of life (i.e., less impairment); the range of possible scores on the GDS-SF is 0 –15; the range of possible scores on both
the MCS-12 and the PCS-12 is 0 –100.

ing behavioral rating scales for dementia
as a reference (46, 47), the deficits of the
impaired group were of the type and se-
verity to impair social and occupational
functioning. For example, the impaired
patients likely have recent memory prob-
lems sufficient to interfere with everyday
activities, decreased ability to perform
complex tasks or handle complicated
problems, and decreased ability to inde-
pendently perform business, financial, or
community affairs. Impairment in visuo-
construction—a complex neuropsycho-
logical domain involving planning, per-
ceptual organization, and visual
memory—would likely lead to difficulties
in such tasks as driving, map reading, and
assembling common household items
such as children’s toys or a set of book-
shelves.
The frequency of impairment in our
patients was much higher than the prev-
alence of mild dementias in older popu-
lation-based samples (48). Our finding of
serious neuropsychological dysfunction
in 11 of 34 patients is more than ten
times higher than the expected number
of patients with mild dementia at a sim-
ilar or greater age (49).
The precise etiology of the neuropsy-
chological impairment in our patients is
unclear, although there is little doubt
that it is multifactorial. Chief among pos-
sible explanations is that the toxic effects
of syndromes such as acute lung injury
and sepsis may cause brain damage, pos-
sibly due to the systemic nature of in-
flammatory and coagulopathic derange-
ments found in these processes (16, 18).

Crit Care Med 2003 Vol. 31, No. 4 1231


P
rolonged neuro-
psychological im-
pairment is com-
mon among survivors of the
medical intensive care unit
and occurs with greater than
anticipated frequency when
compared with relevant nor-
mative data.
Another likely culprit is hypoxemia,
which has already been implicated in nu-
merous investigations regarding the de-
velopment of cognitive dysfunction (18,
50, 51). Although we did not demonstrate
a significant relationship between delir-
ium and neuropsychological decline, this
investigation was not powered to detect
this association, and its absence may re-
flect a type II error. We believe that future
studies of larger cohorts should examine
the association of severe or prolonged
delirium and negative long-term cogni-
tive outcomes (20, 28, 29, 52–55). Psy-
choactive medications, used extensively
and in significant doses among critically
ill patients, may play a causal role in the
persistence of cognitive deficits even
months after their discontinuation (56 –
58, 59). The lower education levels found
among impaired patients may be signifi-
cant as well, particularly in light of data
showing education to be protective
against the development of neuropsycho-
logical deficits (60, 61). In addition, al-
though it appears unlikely that age was
the sole reason for the impairment ob-
served among our patients, it may also be
that their greater age made them partic-
ularly vulnerable to neuropsychological
insults (62). Whereas our multivariable
analysis confirmed highly significant dif-
ferences in the neuropsychological pro-
files of our impaired vs. nonimpaired pa-
tients even after adjusting for age,
educational level, and baseline dementia,
future studies enrolling larger numbers
of patients would clearly be more capable
of determining the interactions between
these covariates and long-term neuropsy-
chological sequelae.
Our documentation of depressed qual-
ity-of-life scores in the population as a
1232
whole is consistent with emerging find-
ings that demonstrate an association be-
tween cognitive deficits and diminished
quality of life (63, 64). Although physical
illness has long been associated with poor
quality of life (65, 66), it is increasingly
apparent that even mild cognitive diffi-
culties can have an adverse impact as well
(67) and that cognitive impairment is as-
sociated with functional decline and a
decrease in subjective well-being (68).
The prevalence of clinically significant
depression in our sample of both im-
paired and nonimpaired patients is within
expected ranges based on relevant litera-
ture that estimates that up to 30% of
elderly patients experience depression
while in the hospital (69) and that as
many as 40% of medically ill patients are
depressed up to a year after hospital dis-
charge (70). Although the precise causes
of depression among the patients in our
sample are unclear, they are likely related
to the variables of medical illness, neuro-
psychological dysfunction, diminished
quality of life, and in some cases, ad-
vanced age—all of which have been re-
ported to be risk factors for depression
(71, 72).
In addition to the small sample size of
our study, an additional important limi-
tation of the present study was that pre-
existing cognitive impairment was iden-
tified by chart review and surrogate
interview rather than by previous psycho-
metric testing. It is important to ac-
knowledge that this will be an inevitable
reality of all similar studies in which the
ICU population is admitted “nonelec-
tively” due to critical illness. We used a
sensitive cutoff score for the mBDRS to
eliminate those patients with any detect-
able baseline deficits to avoid falsely at-
tributing their decline to factors related
to mechanical ventilation, critical illness,
or ICU hospitalization. Furthermore, the
low test scores in our 11 impaired pa-
tients indicate deficits of a severity that
presumably would have been identified by
a close informant, if not documented in
patient medical records, had they been
preexisting. Another limitation of this
study was that we did not formally assess
the work status or activities of daily living
of the cohort at long-term follow-up. In-
vestigations of these issues would be
helpful in determining the functional im-
pact of neuropsychological impairment.
The current investigation provides ev-
idence of the prevalence of cognitive im-
pairment in patients after ICU hospital-
ization and contributes to a growing body
of research documenting the negative
neuropsychological outcomes associated
with critical illness. Neuropsychological
impairment is problematic for numerous
reasons and generally contributes to
strain on family and social support net-
works, reduced occupational capacity, di-
minished life satisfaction, and the in-
creased utilization of resources (73–78).
These results provide a mandate for both
critical care physicians and health ser-
vices researchers to invest their consid-
erable energies toward recognizing, un-
derstanding, and intervening in ways that
will minimize the development and con-
sequences of prolonged cognitive impair-
ment in ICU survivors.
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