Archives of Clinical Neuropsychology 23 (2008) 809822

Effects of day-of-injury alcohol intoxication on neuropsychological

outcome in the acute recovery period following traumatic
brain injury
Rael T. Lange a, , Grant L. Iverson a , Michael D. Franzen b
a

British Columbia Mental Health and Addiction Services & University of British Columbia, Canada
b Allegheny General Hospital, Canada
Accepted 21 July 2008

Abstract
Some researchers have found that day-of-injury alcohol intoxication is associated with worse outcome following traumatic brain
injury (TBI). The purpose of this study is to examine the effects of day-of-injury intoxication on the acute neuropsychological
outcome from TBI. Participants were 36 patients with TBI (18 sober, 18 intoxicated) matched on injury severity characteristics
and demographic variables. A larger group of 146 patients (112 sober, 36 intoxicated) with TBI was also selected for analyses; not
matched on injury severity or demographic variables. Patients had no history of pre-injury alcoholism and were assessed within 10
days post-injury on 13 cognitive measures. Unexpectedly, patients who were sober at the time of injury performed lower on many
of the cognitive measures compared to those who were intoxicated. In contrast to the research literature, these results suggest that
individuals who were intoxicated at the time of injury performed similarly, and in some cases, better than those who were sober at
the time of injury.
Crown Copyright 2008 Published by Elsevier Ltd on behalf of National Academy of Neuropsychology. All rights reserved.
Keywords: Ethanol; Head injury; Cognition; Neurocognitive; Acute outcome; Risk factors

1. Introduction
Individuals who sustain a traumatic brain injury (TBI) are frequently intoxicated with alcohol at the time of injury
(Brismar, Engstrom, & Rydberg, 1983; Edna, 1982; Kaplan & Corrigan, 1992; Sparadeo, Strauss, & Barth, 1990). The
prevalence of positive blood alcohol levels (BAL) in hospital patients presenting to the Emergency Department (ED)
with head trauma ranges from 33% to 72% (e.g., Corrigan, 1995; Dikmen, Machamer, Donovan, Winn, & Temkin,
1995; Gurney et al., 1992; Kreutzer, Doherty, Harris, & Zasler, 1990; Rimel & Jane, 1983; Solomon & Malloy, 1992;
Sparadeo & Gill, 1989; Sparadeo et al., 1990), with 3753% having BALs that exceed the legal limit for intoxication
(Gurney et al., 1992; Kraus, Morgenstern, Fife, Conroy, & Nourjah, 1989; Rimel, Giordani, Barth, & Jane, 1982).
Day-of-injury alcohol intoxication has significant implications for the diagnosis, management, treatment, and recovery

A portion of these data were presented at the annual conference of the Research Society on Alcoholism, July 2007, Chicago, Illinois, USA.
Corresponding author at: BC Mental Health and Addiction Services, Suite 201, 601 West Broadway, Vancouver, BC V5Z 4CZ, Canada.
Tel.: +1 604 707 6374; fax: +1 604 707 6399.
E-mail address: rlange@bcmhs.bc.ca (R.T. Lange).

0887-6177/$ see front matter. Crown Copyright 2008 Published by Elsevier Ltd on behalf of National Academy of Neuropsychology. All rights reserved.

doi:10.1016/j.acn.2008.07.004

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R.T. Lange et al. / Archives of Clinical Neuropsychology 23 (2008) 809822

from TBI. Patients who present to the ED with a positive BAL are more difficult to manage and treat, have a slower
acute recovery (Barker et al., 1999; Brismar et al., 1983; Cunningham, Maio, Hill, & Zink, 2002; Gururaj, 2004; Kaplan
& Corrigan, 1992; Kraus et al., 1989; Wilde et al., 2004), and consequently place an increased economic burden on
the health care system.
The effects of day-of-injury alcohol intoxication on the neuropsychological and neuropathological outcome from
TBI have received modest attention in the research literature. Researchers have reported that patients who are intoxicated at the time of TBI have worse cognitive recovery (Bombardier & Thurber, 1998; Kelly, Johnson, Knoller,
Drubach, & Winslow, 1997; Sparadeo & Gill, 1989; Tate, Freed, Bombardier, Harter, & Brinkman, 1999; Wilde et al.,
2004) and greater atrophic changes in the brain (Barker et al., 1999; Wilde et al., 2004) compared to those who are
sober. Specifically, individuals who are intoxicated at the time of injury (a) have worse global cognitive and neurobehavioral status at discharge as measured by the Rancho Los Amigos Scale (Sparadeo & Gill, 1989), (b) show greater
trauma induced degenerative changes post-injury as indicated by higher ventricle-to-brain ratio and lower whole brain
volume (i.e., grey and white matter) (Barker et al., 1999; Wilde et al., 2004), and (c) perform more poorly on measures
of verbal ability, visuospatial ability, immediate and delayed memory, processing speed skills, and executive functioning (Bombardier & Thurber, 1998; Kelly, Johnson, et al., 1997; Tate et al., 1999; Wilde et al., 2004). Although
some studies have reported findings that are inconsistent with this premise (Barker et al., 1999; Bigler et al., 1996;
Lange, Iverson, & Franzen, 2007b; Vickery et al., 2008), the majority of the research literature in this area provides
support for the presence of a deleterious interaction between day-of-injury alcohol intoxication and outcome from
TBI.
It has been suggested that worse outcome following day-of-injury alcohol intoxication may be the result of an
increased magnitude of brain injury resulting from a variety of negative responses in the brain not present in a
person who is sober at the time of injury. Negative responses include, but are not limited to, hemodynamic and
respiratory depression, altered homeostasis due to increased blood clotting time, bloodbrain barrier impairment,
and/or increased risk for developing hematomas (Alexander, Kerr, Yonas, & Marion, 2004; Altura & Altura, 1999;
Altura, Memon, Altura, & Cracco, 1995; Barker et al., 1999; Kelly, 1995; Mautes et al., 2001; Sparadeo & Gill,
1989; Wilde et al., 2004; Woolf, Cox, Kelly, McDonald, & Hamill, 1990; Zink & Feustel, 1995; Zink et al., 2001).
However, researchers have reported a significant relationship between day-of-injury alcohol intoxication and premorbid history of alcohol abuse in TBI samples (Dikmen et al., 1995; Kreutzer et al., 1996; Sparadeo & Gill,
1989), with up to 75% of patients who are intoxicated at the time of injury having a positive history of pre-injury
chronic alcoholism (Bombardier, 1995). Regardless of BAL at the time of injury, prevalence rates of chronic alcoholism in all TBI patients range from 25% to 79% (Bogner, Corrigan, Mysiw, Clinchot, & Fugate, 2001; Corrigan,
1995; Corrigan, Bogner, Mysiw, Clinchot, & Fugate, 2001; Kolakowsky-Hayner et al., 1999; Kreutzer et al., 1990;
Rimel et al., 1982; Sparadeo & Gill, 1989; Tobis, Puri, & Sheridan, 1982). As such, worse outcome may simply reflect the effects of pre-injury alcohol abuse that is very common in this patient population (e.g., Barker et
al., 1999; Bogner et al., 2001; Corrigan et al., 2001; Fein, Fletcher, & Di Sclafani, 1998; Kolakowsky-Hayner et
al., 1999; Paraherakis, Charney, & Gill, 2001; Parsons, 1998; Pfefferbaum & Sullivan, 2002; Pfefferbaum et al.,
2000).
The influence of pre-injury alcohol abuse on poor outcome following intoxicated TBI cannot be underestimated.
Researchers attempting to differentiate the contribution of day-of-injury alcohol intoxication from pre-injury chronic
alcohol abuse have found mixed results. Some studies have clearly supported the influence of alcohol intoxication
at the time of injury as more influential in determining neuropsychological and neuropathological outcome than
pre-injury alcohol abuse history (Brooks et al., 1989; Tate et al., 1999), other studies have found pre-injury alcohol
abuse to be more influential than day-of-injury intoxication (Lange et al., 2007b), or have reported that day-ofinjury intoxication and pre-injury alcohol abuse are equally important (Wilde et al., 2004) or non-contributory factors
(Vickery et al., 2008). Although these studies do not provide us with clear answers regarding the competing influence
of these two alcohol variables on outcome from TBI, this research highlights the methodological importance of
controlling for the effects of pre-injury alcohol consumption in research examining the effects of day-of-injury alcohol
intoxication.
The purpose of this study is to examine the effects of day-of-injury alcohol intoxication on the acute neuropsychological outcome (i.e., within the first 10 days post-injury) from TBI in a sample of patients with no pre-injury alcohol
abuse. It is hypothesized that patients who are intoxicated at the time of injury will have worse neuropsychological
outcome compared to those who were sober at the time of injury.

R.T. Lange et al. / Archives of Clinical Neuropsychology 23 (2008) 809822

811

2. Method
2.1. Participant pool and selection procedure
Participants were selected from an archival database of 2160 patients seen as part of the Allegheny General Hospital
(AGH) trauma service clinical pathway in Pittsburgh, Pennsylvania, for a known or suspected TBI. These patients
presented to the trauma service during the period of 19911994 and 20022003. The basic clinical pathway for any
person with known or suspected brain injury, irrespective of severity, involved a Glasgow Coma Scale (GCS) rating
obtained on admission to the trauma centre (by emergency department personnel), head X-ray, CT scan of the brain,
and an assessment of post-traumatic amnesia with the Galveston Orientation and Amnesia Test (Levin, ODonnell, &
Grossman, 1979). Only those patients with a definite TBI were of interest, defined by the following criteria: (a) evidence
of skull fracture on X-ray, (b) evidence of trauma-related brain abnormality (e.g., edema, hematoma, or contusion) on
CT-scan, and/or (c) a Glasgow Coma Scale score of eight or less. Of the sample, 667 patients (42.4%) were classified
as sustaining a definite TBI.
Patients were further selected for inclusion if they had a blood alcohol level (BAL) measured as part of a toxicology
screen on admission (n = 524; 78.6%). Toxicology screening at the time of admission is fairly routinely undertaken
by the trauma service; however, some patients do not receive a toxicology screen (n = 143, 21.4%; e.g., not ordered
or refusal). Alcohol intoxication was defined as a BAL of 100 mg/dl or higher, consistent with the extant research
literature. Of the patients who received a toxicology screen, the prevalence of (a) any detectable alcohol (i.e., BAL > 0)
at the time of injury was 53.4% (n = 280), (b) intoxication (i.e., BAL 100 mg/dl) at the time of injury was 49.2%
(n = 258), and (c) sobriety at the time of injury (i.e., BAL = 0 mg/dl) was 50.8% (n = 266). Patients were only selected
if their BAL at the time of admission was 0 mg/dl or 100 mg/dl (n = 480, 91.6%). Patients with BAL between 1 mg/dl
and 99 mg/dl were excluded in order to create two distinct BAL groups.
Patients were further selected for inclusion if they had available information regarding their pre-injury alcohol use
(n = 360, 75.0%). Pre-injury alcohol use was determined by a chart review and patient interview by the neuropsychologist on duty at the time evaluation. Patients with a significant history of pre-injury alcohol use were targeted
for exclusion. Pre-injury alcohol abuse was classified as present when (a) the patients medical records indicated a
history of abuse or treatment, or heaving drinking [i.e., more than 56 drinks a few times per week] and (b) if the
patient reported, during interview, a history of abuse or treatment, or heavy drinking. Patients classified as having a
significant pre-injury alcohol abuse history represent a relatively mixed group of individuals whose pre-injury alcohol
abuse varied from mild to severe. Detailed information relating to duration, frequency, and degree of pre-injury alcohol
abuse was not coded and entered into the database, and is not available. Nonetheless, representative patients in this
category who were excluded were those patients (a) with a current addiction problem at the time of injury, (b) who
participated in a rehabilitation treatment program several years prior to injury, (c) who participated in a rehabilitation
treatment program just prior to injury, (d) had a history of addiction in the past, (e) who reported to consume 56 alcoholic drinks a few times a week, and/or (f) who reported to consume more than 5 drinks per day. Of the 360 patients
with available information, 50.8% (n = 183) had a positive pre-injury alcohol abuse history and 49.2% (n = 177) had a
negative pre-injury alcohol abuse history.
All patients presenting to the trauma service with a known or suspected traumatic brain injury were referred to the neuropsychology service for consultation. A brief neuropsychological battery was administered to document the patients
cognitive status in terms of attention, memory, language, and executive functions. In order to control for the effects of
testing time post-injury, only those patients who were tested within 10 days of injury were selected for inclusion (n = 148,
86.4%; TBI Sober, n = 112; TBI Intoxicated, n = 36 [BAL: M = 158.4 mg/dl, S.D. = 41.5, range = 100268 mg/dl; participants with BAL > 200 mg/dl = 4]). In many cases however, all measures were not routinely administered due to
time constraints and/or other factors (such as orthopedic injuries). Only those patients who had been administered
the entire battery of tests were included (n = 95, 62.1%). Of this group, 25.3% of patients (n = 24) were intoxicated
(i.e., BAL 100 mg/dl) at the time of injury, and 74.7% of patients (n = 71) were sober at the time of injury (i.e.,
BAL = 0 mg/dl).
Through sorting and visual inspection, an attempt was made to match the 24 patients who were intoxicated at the
time of injury with a patient who was sober. Patients were matched based on (a) injury severity classification [e.g.,
complicated mild TBI, mild TBI with skull fracture, moderate TBI, and severe TBI], (b) ethnicity, (c) days post-injury
[2 days], (d) age [5 years], and (e) education [2 years]. Patients who could not be matched on all five criteria

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R.T. Lange et al. / Archives of Clinical Neuropsychology 23 (2008) 809822

Table 1
Demographic and injury severity characteristics
TBI Sober

Age (in years)

Education (in years)
GCS score
Days tested post-injury

TBI Intoxicated

S.D.

S.D.

26.8
12.4
11.5
5.0

8.8
1.7
4.8
2.6

27.6
12.6
11.3
3.6

9.4
1.5
5.2
2.6

TBI Sober
N
Gender
Male
Female

TBI Intoxicated
%

12
6

66.7
33.3

12
6

66.7
33.3

6
6
6

33.3
33.3
33.3

6
6
6

33.3
33.3
33.3

LOC
Positive
Negative
Equivocal

12
2
4

66.7
11.1
22.2

10
3
5

55.6
16.7
27.8

Mechanism of injury
MVA/MCA
Falls
Pedestrian struck MV
Object/blow/assault
Other

12
2
2
0
2

66.7
11.1
11.1

11.1

9
1
2
2
4

50.0
5.6
11.1
11.1
22.2

CT scan
Normal
Abnormalities
Missing

5
12
1

27.8
66.7
5.5

5
12
1

27.8
66.7
5.5

Data collection period

19911993
20022003

17
1

94.4
5.6

15
3

83.3
16.7

Injury severity
MTBI with skull Fx
Complicated MTBI
Severe TBI

Note: n = 36 (TBI Sober, n = 18; TBI Intoxicated, n = 18); CT = computed tomography; GCS = Glasgow Coma Scale; LOC = loss of consciousness;
MTBI = mild traumatic brain injury; TBI = traumatic brain injury; MVA = motor vehicle accident; MCA = motor cycle accident; MV = motor vehicle.

were not included. Of the 24 patients who were intoxicated at the time of injury, 18 patients were matched successfully
to 18 patients who were sober. All other patients were excluded from the final sample. The results, as seen in Table 1,
were two closely matched groups on demographic and injury severity variables.
2.2. Participant description
The participants in the final sample were 36 patients (i.e., 18 sober [0 mg/dl]; 18 intoxicated [100 mg/dl; M = 151.6,
S.D. = 33.1, range = 100248 mg/dl] with definite TBI and no history of alcohol abuse or other substances. More than
half of the patients (61.1%) were assessed within 4 days after presenting to the trauma service, with all patients assessed
within 10 days. The average age and education of the sample was 27.2 years (S.D. = 9.0) and 12.5 years (S.D. = 1.6),
respectively. There were no significant differences between TBI-sober versus TBI-intoxicated groups in the number of
days tested post-injury (p = .308), age (p = .755), or education (p = .558). Sex of the sample was predominantly male
(66.7%). Mechanism of injury was predominantly motor vehicle accident with no seatbelt (41.7%), followed by motor
vehicle accident with seatbelt (11.1%), and pedestrian struck by a motor vehicle (11.1%). The breakdown of injury

R.T. Lange et al. / Archives of Clinical Neuropsychology 23 (2008) 809822

813

Table 2
Descriptive statistics, ANOVA results, and effect sizes by group
Measures

Logical Memory I
Logical Memory II
LM % Savings
Visual Rep I
Visual Rep II
VR % Savings
Digit Span: Forward
Digit Span: Backward
Trails A
Trails B
COWAT: CFL
WCST-64 Categories
WCST-64 PE

TBI Sober

TBI Intoxicated

S.D.

S.D.

21.0
12.8
56.3
31.8
24.7
75.8
8.0
4.7
32.7
97.1
29.7
2.4
16.4

6.0
8.8
34.1
6.5
10.9
32.4
1.8
1.8
18.7
57.9
9.5
1.4
11.7

24.5
19.1
76.0
34.6
31.9
91.4
8.9
5.7
27.0
61.4
35.3
3.7
8.8

6.7
7.7
19.6
4.6
6.9
12.5
1.8
2.4
7.7
21.0
13.1
1.2
4.4

Effect size

.109
.028
.041
.148
.023
.066
.151
.197
.242
.019
.158
.009
.015

0.55
0.77
0.73
0.50
0.82
0.69
0.50
0.44
0.43
0.91
0.50
0.92
0.94

Medium
Large
Medium-Large
Medium
Large
Medium-Large
Medium
Small-Medium
Small-Medium
Large
Medium
Large
Large

Note: n = 36 (TBI Sober, n = 18; TBI Intoxicated, n = 18). Cohens (1988) effect size (d): small (.20), medium (.50), large (.80). LM = Logical
Memory; Visual Rep/VR = Visual Reproduction; COWAT = Controlled Oral Word Association Test, CFL Letters; WCST-64 = Wisconsin Card Sort
Test-64; PE = Perseverative Errors.

severity for the sample was 33.3% for mild TBI with skull fracture [i.e., GCS score = 13 to 15 with a skull fracture on
X-ray, but no intracranial CT abnormality], 33.3% for complicated mild TBI [i.e., GCS score = 13 to 15 and abnormal
day-of-injury CT], and 33.3% for severe TBI [i.e., GCS score < 9 and abnormal day-of-injury CT (e.g., presence of
cerebral contusion, swelling, or intracranial hematoma]. The breakdown regarding loss of consciousness was 61.1%
positive, 13.9% negative, 5.6% equivocal, and 19.4% unknown. Ethnicity of the sample was predominantly Caucasian
(94.6%). There were an identical number of patients between groups for gender, ethnicity, and injury severity categories.
There were no significant differences in the proportion of patients in each group for mechanism of injury (p = .277) or
loss of consciousness (p = .300). Given that the trauma patients were seen in the first few weeks post-injury, as part of
the trauma clinical pathway, it is unlikely that they had major incentives to malinger at the time of evaluation. However,
effort was not formally assessed.
2.3. Measures
The cognitive measures were the Trail Making Test [TMT] (Reitan, 1992): Part A and Part B; Controlled Oral Word
Association Test [COWAT] (Benton, Hamsher, & Sivan, 1994): Total letters CFL; Wisconsin Card Sorting Test-64
Card Version [WCST-64] (Kongs, Thompson, Iverson, & Heaton, 2000): Total Categories and Perseverative Errors;
and selected subtests from the Wechsler Memory Scale-Revised [WMS-R] (Wechsler, 1987): Digit Span Forward
and Backward, Logical Memory I and II, Visual Reproduction I and II. Savings scores for the Visual Reproduction
and Logical Memory subtests were also included in the analyses. Savings scores represent a ratio (presented as a
percentage) of the amount of information recalled after a delay relative to the initial acquisition of information. This
is calculated by dividing the delayed recall score by the immediate recall score and multiplying this product by 100
(e.g. [Logical Memory II/Logical Memory I] 100). These measures were selected based on the available data in the
AGH Trauma database. These measures were originally selected by the AGH clinicians to provide a brief evaluation
of neuropsychological functioning as soon as practical following injury. Raw scores were used in the analysis unless
otherwise stated. A total of 13 cognitive measures were considered in all.
3. Results
A series of one-way ANOVAs were conducted using the 13 cognitive measures as dependent variables and day-ofinjury alcohol intoxication status as the independent variable (i.e., TBI-Sober & Intoxicated). The use of MANOVA
was precluded by the relatively small sample size and large number of dependent variables. Descriptive statistics,
ANOVA results, and effect sizes (Cohen, 1988) for the 13 cognitive measures by group are presented in Table 2.

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R.T. Lange et al. / Archives of Clinical Neuropsychology 23 (2008) 809822

There were significant main effects on six of the 13 cognitive measures (range: p = .009 to p = .041). Overall, patients
who were sober at the time of injury performed worse on tasks of delayed verbal memory (Logical Memory II and
LM % Savings), delayed visual memory (Visual Reproduction II), and executive functioning (Trails B, WCST-64
Categories, and WCST-64 Perseverative Errors) compared to those who were intoxicated at the time of injury. For
all comparisons, the effect sizes were large, ranging from d = 0.73 to d = 0.94. Medium effect sizes were found on
four additional cognitive measures (d = .50 to .55), although not statistically significant likely due to small sample
size (p = .109 to .158). For these measures, patients who were sober at the time of injury again performed worse on
tasks of immediate verbal memory (Logical Memory I), immediate visual memory (Visual Reproduction I), immediate
attention span (Digit Span forward), and verbal fluency (COWAT: CFL).
Additional analyses were undertaken based on the clinical interpretation of these measures. Raw scores were
converted to percentile scores using the following published norms: (a) WMS-R manual for Logical Memory I and
II, Digit Span Forward and Backward, and Visual Reproduction I and II (Wechsler, 1987), (b) normative tables by
Prifitera and Ledbetter (1992) for Logical Memory and Visual Reproduction savings scores (Spreen & Strauss, 1998),
(c) WCST-64 manual for Total Categories and Perseverative Errors (Kongs et al., 2000), (d) TMT Part A and B
completion time normative data by Heaton and colleagues (Heaton, Miller, Taylor, & Grant, 2004), and (e) COWAT
normative data for the letters CFL by Ruff and colleagues (Ruff, Light, Parker, & Levin, 1996). The percentages of
patients with scores less than the 10th percentile and 16th percentile on each of the 13 cognitive measures by group are
presented in Table 3. Chi-square analysis was used to compare the proportion of low scores on each measure between
groups. In some analyses, the expected frequencies of cells were less than five and Fishers Exact Test statistics were
interpreted. Cutoff scores at the 1st percentile, 10th percentile, and 16th percentile are often used by clinicians to infer
degrees of cognitive impairment. However, a cutoff score at the 1st percentile was not included in these analyses due
to the low prevalence of scores in this range.
Overall, there was a greater number of low scores in the TBI-sober group compared to the TBI-intoxicated group.
Using the 10th percentile cutoff score, the prevalence of low scores on the 13 individual cognitive measures in the
Sober-TBI group ranged from 5.6% (Digit Span Forward) to 50.0% (LM % Savings), with 11 of the 13 measures
having a prevalence rate greater than 22.1%. For the TBI-Intoxicated group, the prevalence of scores falling below the
10th percentile on the 13 cognitive measures ranged from 5.6% (e.g., Digit Span Forward, Trails A) to 16.7% (LM %
Savings), with 10 of the 13 measures having a prevalence rate less than 11.2%. Chi-square analyses revealed significant
differences in the proportion of low scores between groups on three of the 13 measures (all p < .05; LM % Savings, VR
% Savings, WCST-64 Categories). However, the small sample size likely masked other differences between groups.
Using the 16th percentile cutoff score, the prevalence of low scores on the 13 cognitive measures in the Sober-TBI
group ranged from 27.8% (e.g., Trails A, Visual Reproduction I and II) to 50.0% (e.g., LM % Savings, WCST-64
Table 3
Prevalence of low scores on each cognitive measure by group
Measures

TBI Sober (<10th)

TBI Intoxicated (<10th)

TBI Sober (<16th)

TBI Intoxicated (<16th)

Logical Memory I
Logical Memory II
LM % Savings
Visual Reproduction I
Visual Reproduction II
VR % Savings
Digit Span: Forward
Digit Span: Backward
Trails A
Trails B
COWAT: CFL
WCST-64 Categories
WCST-64 PE

27.8
33.3
50.0a
22.2
22.2
38.9a
5.6
33.3
16.7
27.8
27.8
44.4b
27.8

11.1
11.1
16.7a
5.6
11.1
11.1a
5.6
16.7
5.6
5.6
16.7
5.6b
5.6

33.3
50.0a
50.0
27.8
27.8
38.9
22.2
44.4
27.8
38.9
33.3
50.0a
50.0

11.1
11.1a
22.2
5.6
16.7
16.7
11.1
38.9
16.7
22.2
22.2
16.7a
22.2

Note: n = 36 (TBI Sober, n = 18, TBI Intoxicated, n = 18). Fishers Exact Test; a p < .05; b p < .01, LM = Logical Memory; VR = Visual Reproduction;
COWAT = Controlled Oral Word Association Test, CFL Letters; WCST-64 = Wisconsin Card Sort Test-64; PE = Perseverative Errors. Fishers Exact
Test was used for the majority of comparisons with the exception of LM % Savings and the following measures using the 16th percentile criterion:
LM II, VR % Savings, Digit Span Backward, Trails B, COWAT-CFL, and the WCST-64.

R.T. Lange et al. / Archives of Clinical Neuropsychology 23 (2008) 809822

815

Categories), with 10 of the 13 measures having a prevalence rate of greater than 33.2%. For the TBI-Intoxicated group,
the prevalence of low scores on the 13 cognitive measures ranged from 5.6% (e.g., Visual Reproduction I) to 38.9%
(Digit Span Backwards), with 12 of the 13 measures having a prevalence rate of less than 22.3%. Chi-square analyses
revealed significant differences in the proportion of low scores between groups on two measures (all p > .05, Logical
Memory II, WCST-64 Categories).
3.1. Additional analyses
Given that the results of this study were in the opposite direction of the expected hypothesis, a second set of analyses
was also undertaken using a larger sample of patients. This sample included those patients that were selected prior
to exclusion due to the failure to complete all neuropsychological test measures, and prior to the application of the
matching procedure. In sum, the patients included in the larger sample had (a) sustained a definite TBI, (b) had a
BAL of 0 mg/dl or 100 mg/dl, (c) had a confirmed absence of a history of pre-injury alcohol abuse, and (d) were
tested within 10 days of injury (n = 148; TBI Sober, n = 112; TBI Intoxicated, n = 36 [BAL: M = 158.4, S.D. = 41.5,
range = 100268]). Demographic and injury severity characteristics of this sample are presented in Table 4. Of this
group, 37.9% had not completed the entire neuropsychological test battery due to time constraints and/or other factors
(such as orthopedic injuries). More than half of the patients (61.5%) were assessed within 6 days after presenting
to the trauma service. There were no significant differences between TBI-sober versus TBI-intoxicated groups in the
number of days tested post-injury (p = .221), GCS score (p = .100), education (p = .451), gender (.731), or injury severity
classification (p = .480). However, a significant difference was found on age (p = .001).
To explore the effect of day-of-injury alcohol intoxication in this sample, a series of one-way ANOVAs were
conducted using the 13 cognitive measures as dependent variables, and day-of-injury alcohol intoxication status as
the independent variable (i.e., TBI-Sober & TBI-Intoxicated). Prior to the analyses, the relationship between potential
confounding variables on neuropsychological test performance was examined. A series of regression analyses using
the 13 dependent variables and the following four potential confounding variables were evaluated: (a) age [in years],
(b) education [in years], (c) injury severity [GCS score], and (d) days tested post-injury. Any variable found to be a
significant predictor of neuropsychological test performance was included as a covariate in the ANOVA. Descriptive
statistics, ANOVA results, and effect sizes (Cohen, 1988) for the 13 cognitive measures by group are presented in Table 5.
There were significant main effects on three of the 13 cognitive measures (range: p = .015 to p = .042). Overall,
patients who were sober at the time of injury performed worse on tasks of immediate and delayed visual memory
Table 4
Demographic and injury severity characteristics
TBI Sober

Age (in years)

Education (in years)
GCS score
Days tested post-injury

TBI Intoxicated

S.D.

S.D.

37.1
12.1
12.2
5.8

17.2
2.5
4.3
3.5

26.7
12.4
10.7
4.9

8.5
1.2
5.1
3.4

TBI Sober

TBI Intoxicated

.001
.451
.100
.221
p

Gender
Male
Female

72
40

76.6
23.4

22
14

74.1
25.9

.731

Injury severity
MTBI with skull Fx
Complicated MTBI
Moderate TBI
Severe TBI

29
45
15
23

25.9
40.2
13.4
20.5

8
12
4
12

22.2
33.3
11.1
33.3

.480

Note: n = 148 (TBI Sober, n = 36; TBI Intoxicated, n = 112). GCS = Glasgow Coma Scale; MTBI = mild traumatic brain injury; TBI = traumatic brain
injury.

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R.T. Lange et al. / Archives of Clinical Neuropsychology 23 (2008) 809822

Table 5
Descriptive statistics, ANOVA and ANCOVA results, and effect sizes by group
Measures

Logical Memory I
Logical Memory II
LM % Savings
Visual Rep I
Visual Rep II
VR % Savings
Digit Span-Forward
Digit Span-Backward
Trails A
Trails B
COWAT-CFL
WCST-64 Categories
WCST-64 PE

TBI Sober

TBI Intoxicated

S.D.

S.D.

20.5
14.6
66.0
28.4
22.0
77.2
7.8
5.2
40.3
109.0
30.0
2.9
13.1

7.5
8.9
30.5
8.3
10.7
36.8
2.1
2.2
20.5
60.5
12.0
1.6
11.0

20.7
15.3
67.8
34.0
28.8
82.5
8.1
5.8
30.3
75.2
31.8
3.3
10.2

7.9
9.4
30.8
5.4
9.6
21.0
2.2
2.3
10.8
38.0
11.6
1.5
5.6

Effect size

.909
.592
.794
.042
.028
.290
.557
.447
.172
.015
.300
.478
.169

.03
.06
.06
.74
.65
.16
.12
.27
.55
.62
.16
.27
.30

Very small
Very small
Very small
Medium-Large
Medium-Large
Small
Small
Small
Medium
Medium-Large
Small
Small
Small-Medium

Note: Total possible sample: n = 148 (TBI Sober, n = 36; TBI Intoxicated, n = 112). Actual sample sizes by measure are as follows (TBI Sober/TBI
Intoxicated): Logical Memory I and II, and LM % Savings (88/27), Visual Rep I (90/28), Visual Rep II & VR % Savings (89/28), Digit Span-Forward
(99/33), Digit Span-Backward (98/33), COWAT-CFL (100/35), Trails A (97/31), Trails B (92/30), WCST-64 PE & WCST Categories (86/30). Cohens
(1988) effect size (d): small (.20), medium (.50), large (.80). LM = Logical Memory; Visual Rep/VR = Visual Reproduction; COWAT = Controlled
Oral Word Association Test, CFL Letters; WCST-64 = Wisconsin Card Sort Test-64; PE = Perseverative Errors. Use of covariates in ANOVA: (a)
Age = Visual Rep I, Visual Rep II, Digit Span-Backward, Trails A, WCST-64 Categories; (b) Education = Visual Rep I, Trails A; (c) Days tested
Post-injury = Logical Memory II, Trails A, COWAT-CFL; (d) GCS score = Logical Memory II, VR % Savings, COWAT-CFL.

(Visual Reproduction I and II), and executive functioning (Trails B) compared to those who were intoxicated at the
time of injury. For all comparisons, the effect sizes were medium-large, ranging from d = 0.62 to d = 0.74. A medium
effect size was found on one additional cognitive measure (Trails A, d = .55), although not statistically significant
(p = .172). For this measure, patients who were sober at the time of injury again performed worse compared to their
intoxicated counterparts.
Analyses were again undertaken based on the clinical interpretation of these measures. Raw scores were converted
to percentile ranks using published norms. Chi-square analysis was used to compare the proportion of impaired scores
on each measure between groups.
Overall, there was a higher percentage of low scores in the TBI-sober group compared to the TBI-intoxicated group.
Using the 10th percentile cutoff score, the prevalence of low scores on the 13 individual cognitive measures in the
Sober-TBI group ranged from 10.2% (Digit Span Forward) to 41.2% (COWAT: CFL), with 11 of the 13 measures
having a prevalence rate greater than 26%. For the TBI-Intoxicated group, the prevalence of scores falling below the
10th percentile on the 13 cognitive measures ranged from 7.1% (Visual Reproduction I) to 35.7% (Logical Memory II),
with 10 of the 13 measures having a prevalence rate less than 26%. Chi-square analyses revealed significant differences
in the proportion of low scores between groups on only two of the 13 measures (both p < .05; Visual Reproduction I
and Trails A).
Using the 16th percentile cutoff score, the prevalence of low scores on the 13 cognitive measures in the Sober-TBI
group ranged from 16.3% (Digit Span Forward) to 48.5% (COWAT: CFL), with only five of the 13 measures having
a prevalence rate of less than 41%. For the TBI-Intoxicated group, the prevalence of low scores on the 13 cognitive
measures ranged from 17.9% (Visual Reproduction I) to 40.7% (LM % Savings), with all 13 measures having a
prevalence rate of less than 41%. Chi-square analyses revealed significant differences in the proportion of low scores
between groups on only one measure (p < .05, Trails A).
4. Discussion
The purpose of this study was to examine the effects of day-of-injury alcohol intoxication on the acute neuropsychological outcome (i.e., within the first 10 days post-injury) from TBI in a sample of patients with no pre-injury
alcohol abuse. Two different patient groups were examined: (a) a sample of 36 patients carefully matched on injury

R.T. Lange et al. / Archives of Clinical Neuropsychology 23 (2008) 809822

817

severity and demographic variables, and (b) a larger sample of 148 patients not matched on these variables. Based on
the research literature, it was hypothesized that patients who were intoxicated at the time of injury would have worse
neuropsychological outcome compared to those who were sober. In contrast to the research literature (Bombardier &
Thurber, 1998; Brooks et al., 1989; Kelly, Johnson, et al., 1997; Tate et al., 1999; Wilde et al., 2004), the results from
the matched sample suggests that individuals who were intoxicated at the time injury actually had better neuropsychological outcome in the acute stage of recovery from TBI. In sum, on average, patients who were intoxicated at the
time of injury had higher scores on the neuropsychological measures, and had fewer scores that fell in the impaired
range compared to patients who were sober at the time of injury. In the unmatched sample, these effects were not as
prominent, with fewer differences noted between the two groups. Nonetheless, the results from the larger sample were
also inconsistent with the research literature in which individuals who were intoxicated at the time injury either had
comparable or better neuropsychological outcome compared to their sober counterparts.
It is difficult to explain why these results are inconsistent with the extant research literature suggesting that alcohol
intoxication at the time of injury results in worse neuropsychological outcome following TBI (Bombardier & Thurber,
1998; Brooks et al., 1989; Kelly, Johnson, et al., 1997; Tate et al., 1999; Wilde et al., 2004). There are five main reasons
that may account for these discrepancies. First, previous studies have focused on outcome from TBI ranging from 2 to
3 months post-injury (Barker et al., 1999; Bombardier & Thurber, 1998; Kelly, Johnson, et al., 1997; Tate et al., 1999)
to more than 1.57 years post-injury (Bigler et al., 1996; Brooks et al., 1989; Wilde et al., 2004). It is possible that the
negative effects of day-of-injury alcohol intoxication may not manifest during the first 10 days of recovery, and the
differences noted between groups is the result of other unknown factors. While it does not make biological sense to
suggest that any potential negative neurophysiological effects of acute alcohol intoxication at the time of injury would
have a delayed onset following injury, it is possible that the mid- to long-term recovery trajectory of patients who
are sober at the time of injury may be superior and this benefit is not apparent until later in the recovery trajectory.
Although this is considered an unlikely explanation, future research in this area using a longitudinal research design
would help clarify this issue further.
Second, it is possible that the sample selection procedures used in this study may have influenced our findings
regarding the neuropsychological effects of TBI and concurrent day-of-injury alcohol intoxication. This is particularly
relevant for the matched sample. The goal of the sample selection procedure for the matched sample was to carefully
and systematically control for the effects of a variety of factors that are known to influence cognitive test performance
following TBI (e.g., pre-injury alcohol history, injury severity classification, ethnicity, days tested post-injury, age,
gender, and education). From an initial sample of 2160 patients, 36 patients were included in this study, carefully
matched on these variables. Patients that could not be matched on these variables were not included. Statistical
comparisons between groups revealed no differences on all relevant demographic variables and injury-related variables.
Given the rigorous sample selection procedure employed here, it would be difficult to obtain a more closely matched
sample using this population. However, one potential source of bias that may have occurred in the selection of the
matched sample relates to the exclusion of patients who did not complete the entire battery of neuropsychological tests.
It is possible that the most severely affected patients were unable to complete all tests and were thus not included in
the matched sample. When a larger unmatched sample was used that consisted of patients that did not complete the
entire battery of tests, the effects of day-of-injury alcohol intoxication was less prominent in this study. When these
two groups are compared, the most notable difference between the matched and unmatched sample was the larger
percentage of impaired scores in the TBI Intoxicated group from the larger unmatched sample (Table 6) compared to
the TBI Intoxicated group in the matched sample (Table 3). It is possible that our selection of patients who had only
completed all neuropsychological tests in the matched group resulted in a bias towards selection of a higher functioning
TBI Intoxicated group. Nonetheless, even when this is taken into consideration, the results from the larger sample are
still inconsistent with past research.
Third, it is possible that the influence of pre-injury alcohol abuse on post-injury neuropsychological status is more
substantial than the effects of day-of-injury alcohol intoxication and previous studies that have not controlled for preinjury alcohol factors have drawn erroneous conclusions (Bombardier & Thurber, 1998; Kelly, Johnson, et al., 1997).
Many studies in this area suffer from a myriad of methodological limitations that preclude us from understanding the
effects of day-of-injury alcohol on cognitive outcome following TBI. The most significant problem is the failure to
adequately measure and control for the effects of pre-injury alcoholism. Other significant problems include not using
BAL to define patients who are intoxicated, and not assessing patients within the same post-injury time period.
However, in support of the day-of-injury alcohol hypothesis, Tate and colleagues (Tate et al., 1999) have provided

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R.T. Lange et al. / Archives of Clinical Neuropsychology 23 (2008) 809822

Table 6
Prevalence of low scores on each cognitive measure by group
Measures

TBI Sober (<10th)

TBI Intoxicated (<10th)

TBI Sober (<16th)

TBI Intoxicated (<16th)

Logical Memory I
Logical Memory II
LM % Savings
Visual Reproduction I
Visual Reproduction II
VR % Savings
Digit Span: Forward
Digit Span: Backward
Trails A
Trails B
COWAT: CFL
WCST-64 Categories
WCST-64 PE

26.1
27.3
33.0
27.2a
28.6
32.6
10.2
30.9
40.6a
37.0
41.2
31.4
22.1

33.3
35.7
29.6
7.1a
21.4
25.0
18.2
15.2
16.1a
20.0
25.7
16.1
13.3

34.1
43.2
44.3
33.7
41.8
42.7
16.3
41.2
47.9a
44.6
48.5
38.4
30.2

33.3
35.7
40.7
17.9
28.6
35.7
21.2
33.3
22.6a
30.0
34.3
29.0
23.3

Note: Total possible sample: n = 148 (TBI Sober, n = 36; TBI Intoxicated, n = 112). Actual sample sizes by measure are as follows (TBI Sober/TBI
Intoxicated): Logical Memory I and II, and LM % Savings (88/27), Visual Rep I (90/28), Visual Rep II & VR % Savings (89/28), Digit SpanForward (99/33), Digit Span-Backward (98/33), COWAT-CFL (100/35), Trails A (97/31), Trails B (92/30), WCST-64 PE & WCST Categories
(86/30). Chi-square test; a p < .05; LM = Logical Memory; VR = Visual Reproduction; COWAT = Controlled Oral Word Association Test, CFL
Letters; WCST-64 = Wisconsin Card Sort Test-64; PE = Perseverative Errors.

one of the most well-controlled studies in this area to date, by examining the influence of blood alcohol level on
post-acute neuropsychological outcome (tested 2.3 months [S.D. = 2.2] post-injury), in a sample of 67 patients with
mild to severe TBI. Using standard least squares regression analyses, Tate and colleagues concluded that BAL at
hospital admission predicted poorer performance on several neuropsychological measures (e.g., delayed recall for
prose material, verbal memory, planning, organization, and visuospatial ability) and accounted for a significant,
unique portion of the variance in these cognitive measures beyond that of variables known to moderate recovery from
TBI, including age, [education], TBI severity, and history of alcohol abuse (p. 776). The results of the current study are
inconsistent with the results of Tate and colleagues. Methodologically, the current study differs to the work by Tate and
colleagues in which the effects of pre-injury alcohol abuse were controlled via exclusion of such patients, rather than by
using statistical methods. Statistically controlling for pre-injury alcohol consumption is a common and well-accepted
statistical procedure. However, given the known influence of chronic alcohol abuse on neuropsychological status, it
may be possible that controlling for this variable by statistical means may not be as effective as we would anticipate.
Fourth, it is possible that the GCS scores in the intoxicated patients are artificially suppressed by BAL, leading
them to appear more severely impaired than they really are. As such, when patients are matched based on GCS scores,
the intoxicated group may actually have less severe injuries than their matched sober counterparts and as a result
will actually do better on cognitive testing. Although it is a common clinical perception that alcohol intoxication
systematically lowers GCS ratings, the research findings in this area do not support such a relationship. Although some
researchers have concluded that GCS scores are lowered by alcohol intoxication and thus fail to provide an accurate
evaluation of brain injury severity (Alexander et al., 2004; Brickley & Shepherd, 1995; Chatham-Showalter et al.,
1996; Galbraith, Murray, Patel, & Knill-Jones, 1976; Jagger, Fife, Vernberg, & Jane, 1984; Kelly, Johnson, et al., 1997;
Shih et al., 2003; Smith-Seemiller, Lovell, & Smith, 1996), a comparable number of studies have found that there are
no effects of BAL on GCS (Albrecht-Anoschenko, Uhl, Gilsbach, Kreitschmann-Andermahr, & Rohde, 2005; Barker
et al., 1999; Christensen, Janson, & Seago, 2001; Hall, Riley, & Swann, 2005; Nath, Beastal, & Teasdale, 1986; Pories
et al., 1992; Sperry et al., 2006; Stuke, Diaz-Arrastia, Gentilello, & Shafi, 2007). The mixed findings in these studies
are largely the result of the lack of control for the influence of brain injury severity. Brain injury obviously depresses
GCS scores. Therefore, if brain injury severity is not statistically or methodologically controlled for, differences in
GCS scores due to alcohol intoxication are likely to be confounded by the influence of brain injury severity in a given
sample. In one of the most well-controlled studies in this area to date, Sperry and colleagues (Sperry et al., 2006)
examined the influence of BAL on GCS scores in a sample of 1075 patients with TBI of all severities. Injury severity
was classified using the Abbreviated Injury Scale (AIS) for brain injuries (AIS range = 3 to 5). When GCS scores were
evaluated separately in each injury severity subgroup, there were no differences in GCS scores between the intoxicated
and non-intoxicated groups, with the exception of those patients with the most severe injuries (AIS score = 5) where

R.T. Lange et al. / Archives of Clinical Neuropsychology 23 (2008) 809822

819

GCS in the intoxicated group was 1.4 points lower than in the non-intoxicated group. In a recent study by our own
research group using the same database as used in the current study (Lange, Iverson, & Franzen, 2007a), we found
that there was no significant relationship between BAL and GCS scores for the majority of patients, with the exception
of those patients who had BALs greater than 200 mg/dl and who had an abnormal day-of-injury CT scan. Given that
the present study includes only one patient with an abnormal CT scans and a BAL > 200 mg/dl (and whose GCS score
was 15), we are confident that the current results are not biased by the effects of BAL on GCS scores.
Fifth, and most controversial of all, it might be possible that day-of-injury alcohol intoxication may have a neuroprotective role in determining neuropsychological outcome following TBI. Some animal research has found that small
to moderate doses of alcohol (e.g., 12.5 g/kg) may have a neuroprotective effect on the brain at the time of injury by
preservation of cognitive abilities (Is et al., 2005; Janis, Hoane, Conde, Fulop, & Stein, 1998; Kelly, Lee, Pinanong, &
Hovda, 1997; Tureci et al., 2004); although not all animal research in this area has supported this conclusion (Biros,
Kukielka, Sutton, Rockswold, & Bergman, 1999; Zink & Feustel, 1995). In animals, it is thought that day-of-injury
alcohol intoxication may have a neuroprotective effect due to the inhibition of NMDA RECEPTOR-mediated excitotoxicity (Cebere & Liljequist, 2003; Chandler, Sumners, & Crews, 1993; Danysz, Dyr, Jankowska, Glazewski, &
Kostowski, 1992; Takadera, Suzuki, & Mohri, 1990). In humans, some studies have suggested that moderate doses of
alcohol (e.g., <230 mg/dl) on the day of severe TBI is associated with reduced mortality (Blondell, Looney, Krieg, &
Spain, 2002; Tien et al., 2006; Ward, Flynn, Miller, & Blaisdell, 1982). However, there is currently no available research
that has suggested that alcohol may have a neuroprotective effect on cognitive deficits following TBI. Although the
results of this study did support a global positive effect of alcohol intoxication on neuropsychological status in the
first 10 days post-injury, we were not able to explore the relationship between dose of alcohol at the time of injury
and neuropsychological outcome. In this study, only a handful of patients had a BAL that was greater than 200 mg/dl
and the effects of moderate versus heavy alcohol consumption was not able to be examined appropriately. As such,
the BAL in the majority of patients in our study could be classified as a moderate dose of alcohol consistent with the
neuroprotective hypothesis.
This study is not without its limitations and the results of must be interpreted with these in mind. First, this study
addresses short-term outcome only (first 10 days post-injury) and does not address medium- or long-term outcome.
The stability of this finding throughout the recovery trajectory is not known. Second, this study did not examine the
effects of day-of-injury alcohol intoxication in a sample of patients with a history of pre-injury alcohol abuse. The
generalizability of these findings in that patient population is unknown. Third, this study included a small sample
size of patients who were intoxicated at the time of injury and the generalizability of these results to all patients
with TBI is limited. There are many practical limitations in obtaining an adequate sample size of patients in this
category. Patients who are intoxicated at the time of injury and have no concurrent pre-injury alcohol abuse represent
a low-prevalence group. However, this group is of most interest to study in an effort to understand the role of day-ofinjury alcohol intoxication on cognition. Fourth, the available information regarding CT scan results was limited to a
simple dichotomous variable, indicating the presence or absence of day-of-injury intracranial abnormality. Information
pertaining to the type or severity of such intracranial abnormality was not available.
Despite these limitations, the methodological strengths of this study should not be overlooked. These strengths
include (a) the use of day-of-injury BAL to categorize intoxication groups, (b) the comparison of neuropsychological
test performance in patients who were assessed within the same time period post-injury [within 10 days], (c) rigorous
control for the effects of pre-injury chronic alcoholism via exclusion of such patients, and (d) carefully matched samples
on demographic and injury-related variables designed to reduce the effects of variables known to effect TBI. Carefully
controlled, prospective, systematic research is needed to assess the relative effects of day-of-injury alcohol intoxication
on short-, medium- and long-term outcome following TBI.

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