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Adults: A Comprehensive
Review
HerbalGram.
2005;67:43-62 American
Botanical Council
by W. David Crews, Jr.,
PhD, David W. Harrison,
PhD, Melanie L. Griffin,
Katherine D. Falwell,
Tara
Crist, Lesley Longest,
Laura Hehemann, and
Stephenie T. Rey
Introduction
In recent years, there
has been increased
interest in the
utilization of ginkgo
(Ginkgo biloba L.,
Ginkgoaceae) leaf
standardized extract (GBE)
for the treatment of
dementia and cognitive
impairment. Much of this
interest has undoubtedly
been related to the
growing number of
research studies and
clinical trials that
have demonstrated the
potential efficacy of
GBE in the treatment of
such disorders. While a
detailed, systemic
review of these studies
is beyond the scope of
this paper, a recent
Cochran Review1 of 33
randomized, doubleblind,
controlled trials that
examined the effects of
GBE on individuals with
acquired cognitive
impairment (including
dementias) concluded
that GBE was associated
with “promising evidence
of improvement in
cognition and function.”
Similarly, there is also
a growing body of
published research that
has focused on the
potential efficacy of
GBE in enhancing the
neuropsychological
processes of “healthy”
adults and those who are
not experiencing (or
without evidence of)
notable cognitive
difficulties (i.e.,
cognitively intact
individuals). Canter and
Ernst2 authored a review
of the effects on
cognitive functioning in
healthy persons in 2002;
however, there appears
to be an absence of more
recent reviews that have
focused solely on such
published studies of GBE.
Thus, the purpose of
this paper is to provide
a comprehensive review
of the published
scientific literature
(through September 2004)
that has examined the
efficacy of GBE(and
unspecified preparations
of ginkgo in one study)
in healthy and
cognitively intact
persons.
The studies reviewed in
this paper are divided
into 2 categories: acute
studies and short- to
long-term
studies. Acute studies
were defined as the
administration of GBE to
healthy/cognitively
intact adults for
2 days or less. Short-
to long-term studies
were defined as the
administration of GBE to
healthy/
cognitively intact
adults for a minimum of
5 days and up to 2 or
more years. This review
contains the
following sections:
Methods, Acute Studies,
Summary of Acute
Studies, Short- to
Long-Term Studies,
Summary of Short- to
Long-Term Studies, and
Conclusions and
Directions for Future
Research.
Method
Using the key words
Ginkgo biloba and
Cognitive (or
Cognition), Ginkgo
biloba and Memory,
Ginkgo
biloba and Healthy,
Ginkgo biloba and
Cognitively Intact, the
authors of this paper
conducted
comprehensive literature
searches in September
2004 of the following
databases: PubMed
(entire
database through
September 2004) and
PsycINFO (entire
database through
September 2004). All
articles
obtained via these
searches were also
reviewed for additional,
related articles that
addressed the efficacy
of ginkgo in healthy and
cognitively intact
persons. Published
studies were selected
for inclusion in this
review if they utilized
only “healthy” and/or
“cognitively intact”
adult participants, and
if they employed
one or more outcome
measures that assessed
the efficacy of ginkgo
on some aspect(s) of
neuropsychological
functioning. It should
be noted, however, that
trials which involved
the
administration of GBE in
combination with other
agents, such as Asian
ginseng (Panax ginseng
C.A.
Meyer, Araliaceae) root
extract, 3-5 or bacopa (Bacopa
monnieri [L.] Pennell,
Scrophulariaceae)6 were
not included in this
review due to the
inability to separate
the specific effects of
GBE from the other
phytomedicinal
preparations.
Acute Studies
A total of 7 published
studies were found which
have examined the acute
neuropsychological
effects of
GBE in healthy
individuals. (Acute
studies were defined as
the administration of
GBE to healthy/
cognitively intact
adults for 2 days or
less.) Table 1 [download
Table 1, pdf file] on
page 54 provides an
overview of these
studies, which are
listed in chronological
order. Table 2 [download
Table 2, pdf file]
provides summaries of
the proprietary GBE
preparations and Table 3
[download Table 3, pdf
file]
provides outcome
measures utilized in the
investigations (see
pages 56 and 57,
respectively). Subhan
and Hindmarch7 were
among the first to
investigate the acute
effects of GBE in
healthy
volunteers. In
particular, 8 healthy
female participants
received 3 different
doses (i.e., 120, 240,
and 600
mg) of GBE
[TanakanA8/TeboninA8,
Dr. Willmar Schwabe
Pharmaceuticals GmbH &
Co., Karlsruhe,
Germany] or a matching
placebo via a
randomized,
double-blind, crossover
design. A battery of
psychological tests was
administered one hour
after each treatment
(see Table 1 for a
listing of the
specific tests
utilized). Among the
extract doses and 4
outcome measures
utilized in the study,
participants exhibited
significant improvement
in their memory scanning
abilities (a decrease in
response latency on the
Sternberg technique)
following ingestion of
600 mg of GBE, as
compared to
placebo. The authors
indicated that these
results were suggestive
of an effect of GBE on
the serial
comparison stage of the
reaction process on the
Sternberg task.
Similarly, Hindmarch8
reported in a French
journal the results of
an investigation
involving 8 healthy
female volunteers that
appears strikingly
similar, if not
identical, to the one
previously co-authored
by
Subhan and Hindmarch.7
As noted in Table 1, the
sample characteristics
(i.e., size,
gender-makeup,
mean age and age range),
study design, duration
of
treatments/assessments,
GBE composition and
doses,
and outcome measures
utilized appeared
identical in both
studies. Furthermore,
the results across the 2
studies appeared
identical, as the
Hindmarch8 study also
indicated significant
improvements in aspects
of participants’
short-term memory
processes, as assessed
via the Sternberg
technique, 1 hour after
ingestion of 600 mg of
the GBE (TanakanA8),
versus placebo. Similar
to the Subhan and
Hindmarch7
study, no significant
effects were found for
any of the other extract
doses or assessment
measures.
In another investigation
published in a French
journal, Warot and
colleagues9 evaluated
the acute
efficacy of 600 mg of 2
GBE preparations
(GinkgoA8 and
TanakanA8), versus a
placebo, on the
psychomotor and memory
performances of 12
healthy female
participants via a
double-blind,
placebocontrolled design
(see Table 1 for a
listing of the specific
tests utilized).
Psychological testing
was
completed before and 1
hour after the ingestion
of each dose. Although
no significant
improvements
were noted for the GBE
treatments on any of the
tests and measures
utilized, as compared to
baseline,
participants’ scores for
image recall (picture
recall) remained
relatively unchanged
during the
TanakanA8 trial, but
decreased under the
placebo and GinkgoA8
conditions.
Rigney, Kimber, and
Hindmarch10 appeared to
be among the first to
include healthy males in
an
examination of the
efficacy of acute doses
of a GBE [Ginkgo Special
Extract LI 1370;
Lichtwer Pharma,
Berlin, Germany] on
memory and psychomotor
performances.
Specifically, their
study compared 4
doses of GBE (i.e.,
total doses of 120, 150,
240, and 300 mg/day),
versus placebo, for 2
days via a
randomized,
double-blind,
placebo-controlled,
5-way cross-over design
in a sample of 36
asymptomatic/
healthy volunteers
(i.e., 22 males, 14
females). Psychometric
test batteries were
administered across the
2 days of each treatment
prior to GBE ingestion
and then hourly until 11
hours post-dosing (see
Table 1
for a listing of the
specific tests
utilized). Findings
indicated that on the
Sternberg short-term
memory
scanning task,
participants exhibited
significantly faster
reaction times for both
120 mg and 300 mg of
GBE, as compared to
placebo, on each of the
2 days of the study.
Participants receiving
240 mg of GBE,
versus placebo,
displayed significantly
faster performances on
the second day of the
trial. It was noted that
this enhancing effect
was most evident for
those taking the 120 mg
dose of GBE and most
pronounced for the
oldest age group (i.e.,
50 to 59 years).
Although no significant
treatment effects were
observed on immediate
and delayed word recall
tasks, both 120 mg and
240 mg increased the
overall
number of words recalled
during the immediate
recall task, with a more
pronounced increase
noted for
the 120 mg dose. On the
Critical Flicker Fusion
(CFF) task, although an
overall treatment effect
was
significant, none of the
GBE doses produced
effects that differed
significantly from
placebo. Participants
who received 120 mg of
GBE, however, exhibited
higher CFF thresholds,
as compared to all other
treatments and placebo,
and their performances
were significantly
higher than those who
ingested 240
mg of the extract. No
other significant
treatment effects were
observed for any of the
remaining outcome
measures. Overall,
Rigney and associates10
indicated that their
results were very
similar to those of
Subhan and Hindmarch7
which also found
improved performances on
the Sternberg memory
scanning
task, but no significant
results on the CFF,
choice reaction time, or
subject ratings of
arousal measures. It
was noted, however, that
as compared to the
Subhan and Hindmarch7
study, the Rigney and
associates10
findings suggested that
(1) a much lower dose of
GBE (i.e., 120 mg versus
600 mg) resulted in the
most
cognitive enhancement
(e.g., working memory),
(2) the effects of GBE
may be dose dependent,
but not
necessarily in a linear
dose-related fashion,
and (3) such enhancing
effects were more likely
to be
displayed by individuals
50 to 59 years old.
The dose-dependent
cognitive effects of
acute GBE administration
in 20 healthy young
adults were also
examined by Kennedy and
colleagues11 via a
double-blind,
placebo-controlled,
multi-dose, balanced,
crossover design.
Participants were
administered 3 different
doses (i.e., 120, 240,
and 360 mg) of a
standardized GBE [GK501;
Pharmaton, SA, Lugano,
Switzerland] or a
matching placebo. The
cognitive
performances of the
participants were
evaluated via a tailored
version of the Cognitive
Drug Research
(CDR) computerized
assessment battery
immediately prior to,
and again at 1, 2.5, 4,
and 6 hours after,
each dose. Four
cognitive performance
factors, derived via
factor analysis of the
CDR battery’s subtests
(i.e., speed of
attention, accuracy of
attention, quality of
memory, and speed of
memory factors), were
utilized as the primary
outcome measures. The
findings indicated
significant improvements
on the speed
of attention factor for
the 2 highest GBE doses
(i.e., 240 and 360 mg)
at time points 2.5, 4,
and 6 hours
post-dose. For the
quality of memory
factor, significantly
enhanced performances
were exhibited by
participants after
ingestion of 120 mg of
GBE at both 1 and 4
hours post-dosing, as
compared to
placebo. A similar
positive trend was also
noted for the 240 mg
dose of GBE for the same
post-dosing
time points. For the
speed of memory factor,
significantly enhanced
speed was demonstrated
on memory
tasks after the
administration of 360 mg
of GBE at 2.5 hours
post-dose, with positive
trends also noted
for the 120 mg and 360
mg at 6 hours
post-dosing.
Alternatively, a
significant reduction in
speed of
memory was noted for the
240 mg dose of GBE,
versus placebo, at 4
hours post-dosing and
this dose
was noted to
“under-perform” the
other doses on the speed
of memory factor at all
post-dose time
points. Similarly, on
the accuracy of
attention factor, a
significant decrease in
accuracy was noted for
the
240 mg dose of GBE at 1
hour post-dose. No
significant treatment
effects were found on 3
mood factors
(i.e., alertness,
contentedness, or
calmness) derived from
the Bond-Lader visual
analogue scales. Taken
together, the authors
noted that (1) cognitive
enhancement following
administration of GBE
was most
evident in participants’
increased speed of
performance on tasks
assessing attention and
(2) such effects
appeared both dose and
time dependent (i.e.,
significant improvement
seen only at the 2
highest doses
and at the 3 later time
points). A different
pattern of effects was
also noted on the
quality of memory factor
with significant
enhancement observed for
the lowest dose (i.e.,
120 mg) at 1 and 4 hours
postdose,
with similar trends
apparent for 240 mg at
the same time points.
Similarly, Scholey and
Kennedy12 documented the
findings of 3 studies
that examined the acute,
dosedependent cognitive
effects of GBE [GK501;
Pharmaton, SA, Lugano,
Switzerland], Ginseng
extract
[G115; aka GinsanaA8,
Pharmaton, SA, Lugano,
Switzerland], and a
combination of the 2
extracts via
double-blind,
placebo-controlled,
balanced, crossover
designs. For the
purposes of this paper,
only the
study involving doses of
GBE will be reviewed.
The GBE study involved a
total of 20 healthy
young
volunteers who were each
administered 3 different
doses (120, 240, and 360
mg) of GBE or a placebo
on separate days. The
participants completed 2
computerized serial
subtraction tasks (i.e.,
Serial Threes
and Serial Sevens) at
each pretreatment
baseline and again after
1, 2.5, 4, and 6 hours
post-dose.
Findings indicated that
all 3 doses of the GBE,
as compared to placebo,
resulted in significant
increases
in the number of Serial
Threes subtractions at
the 4-hour post-dosing
testing session. A
significant
increase in Serial
Threes subtractions was
also observed 6 hours
after ingestion of the
240 mg dose of
GBE. In contrast, 4
hours after the
administration of 120 mg
of the GBE,
significantly more
subtraction
errors were noted on the
Serial Threes task. For
the Serial Sevens task,
while no significant
differences
were noted in the total
number of subtractions
for any of the doses of
GBE, all doses resulted
in
significantly fewer
errors at 2.5 hours
post-dose, as compared
to placebo.
When literature searches
were conducted for the
present paper, the most
recent study of the
acute
cognitive effects of GBE
was conducted by Nathan
and associates,13 which
involved an examination
of
the phytomedicinal
product on the memory
functioning of 11
healthy “older” adults.
In particular,
participants were
administered 120 mg of
GBE [GinkgoforteAA;
Blackmore’s Ltd.,
Balgowlah, NSW,
Australia] or a placebo
during separate sessions
via a repeated measures,
double-blind,
placebocontrolled
design. During each
treatment condition,
participants were
administered a series of
memory
tests from the Cognitive
Drug Research
computerized assessment
system and the Rey
Auditory Verbal
Learning test at
pretreatment baseline
and again at 90 minutes
post-dose. No
significant acute
effects of
120 mg of GBE were found
for any of the memory
tests utilized in the
study. The authors
indicated that
these findings were
consistent with those of
Subhan and Hindmarch7
and Kennedy and
colleagues,11
which also demonstrated
no acute effects of GBE
on memory at a dose of
120 mg.
Summary of Acute Studies
As of September 2004,
there have been a total
of 7 published studies
that have examined the
acute
neuropsychological
effects of GBE in
healthy adults. (Acute
studies were defined as
the administration
of GBE to
healthy/cognitively
intact adults for 2 days
or less.) Two of these
studies (one published
in
English7 and one in
French8), however,
appeared very similar,
if not identical,
particularly in terms of
such features as their
sample characteristics,
methodology/design,
treatments/doses, and
results.
The sample sizes used in
the acute studies were
relatively small and
ranged from a low of
87,8 to a high
of 3610 participants.
All but one10 of these
reports examined more
females than males,
including 3
studies7,8,10 that
involved only females.
With the exception of 2
studies where the mean
age of participants was
43.610 and 58.4613
years, the remaining
acute studies of GBE
utilized participants
whose mean ages fell
between 19.9 and 32
years. While the
majority of the acute
studies involved
younger, versus older,
participants who
reportedly were
“healthy,” only one of
these investigations
appeared to include any
objective measures to
access levels of
cognitive intactness.
All of the acute studies
indicated that they
employed double-blind,
placebo-controlled,
crossover/
repeated measure designs
with the duration of
their GBE
treatments/assessments
ranging from 1 hour
per dose7,8,9 to 2
days.10 In addition to a
placebo, treatments
involved the
administration of
various GBE
preparations that were
identified as follows:
• Tanakan®/Tebonin®,
• EGb 761,
• Ginkgo®,
• Ginkgo Special Extract
LI 1370,
• Ginkgo biloba extract
GK501, and
• GinkgoforteTM.
Five of the acute
studies7,8,10,11,12
evaluated multiple doses
of GBE formulas, while 2
investigations9,13
utilized only a single
dose. The doses of GBE
used in these studies
ranged from a low of 120
mg to a
high of 600 mg.
A diversity of outcome
measures, assessing a
wide range of
neuropsychological
processes, were
administered across the
acute studies ranging
from measures of
reaction time and line
analogue rating
scales, to computerized
assessment batteries
from which
factor-derived scores
were obtained. Among
the most common measures
that were administered
in these studies were
the Critical Flicker
Fusion,
Choice Reaction Time,
Line/Visual Analogue
Rating Scales, and
Sternberg Memory tasks,
as well as
tests from the Cognitive
Drug Research
computerized assessment
battery.
Significant, positive
neuropsychological
effects of a GBE were
found in 5 out of 7
acute studies (4 of 6
if the Subhan and
Hindmarch7 and
Hindmarch8 studies
represent the same
investigation). In
particular,
higher doses (i.e., 240
and 360 mg) of an
extract were shown to
result in improvements
on a factorderived,
speed of attention
factor at 2.5, 4, and 6
hours post-dose and to
significantly enhance a
quality
of memory factor after
the ingestion of 120 mg
of the product at 1 and
4 hours post-dose.11
Furthermore,
while significant
enhancement was found
for 360 mg of the GBE at
2.5 hours post-dose for
a speed of
memory factor, a
significant reduction in
this factor was observed
for the 240 mg dose 4
hours after
ingestion.11 A
significant decrease in
an accuracy of attention
factor was also noted
for a 240 mg dose ofGBE
1 hour after
administration.11 The
authors acknowledged
that these contrasting
findings were not
readily interpretable.
Additional dose and
time-dependent effects
were found for a GBE in
a study that utilized 2
computerized serial
subtraction tasks.12
Specifically, single
doses of 120, 240, and
360 mg of GBE were noted
to significantly
increase the number of
Serial Threes
subtractions (described
as an attentional/
concentration task with
a procedural learning
element) 4 hours post
dose, while a 240 mg
dose increased
subtractions 6 hours
after ingestion. In
contrast, significantly
more errors were made on
the Serial
Threes task following
120 mg of the extract at
4 hours post dose. While
no significant
differences were
observed in the number
of subtractions for any
dose on a Serial Sevens
task (reportedly
involved in
central executive
resources),
significantly fewer
errors were noted after
2.5 hours for all doses.
Although
the precise
interpretation of these
observed effects remain
somewhat difficult, the
authors12 noted that
the results appeared
broadly consistent with
an improved “speed of
attention” factor
following GBE
administration that was
found in their previous
study.11
The acute, positive
effects of a GBE were
also demonstrated in
aspects of participants’
high speed
scanning and retrieval
from short-term memory
processes (as assessed
via the Sternberg Memory
Scanning task) after a
single dose of 600
mg.7,8 Similar, positive
Sternberg results were
exhibited across
a 2-day period for 120
and 300 mg/day doses of
a GBE and for a 240
mg/day dose of the
extract on day
2.10 In contrast, no
significant effects were
found on the Sternberg
task 1 hour after the
ingestion of
single 120 and 240 mg
doses of GBE.7,8 Two
other acute studies,
which administered
either a 120 mg13 or 600
mg9 dose of a GBE,
failed to find
significant positive
effects on the
neuropsychological
processes of healthy
adults. In one of these
studies,9 however, while
no significant
improvements were found
for the GBE treatment on
any of the tests and
measures utilized, as
compared to baseline,
participants’ image free
recall scores remained
relatively unchanged
during a trial of
TanakanA8, but decreased
under the placebo and
GinkgoA8 conditions.
A diversity of factors
may have contributed to
the general absence of
positive results in
these 2
investigations.
Specifically, upon
comparison of the Warot
et al9 study to the one
conducted by Subhan
and Hindmarch7 (and
Hindmarch8), which also
administered a 600 mg
dose of a GBE, the mean
age of
participants in the
Warot trial9 was almost
a decade younger than
the mean age of
participants in the
Subhan and Hindmarch
study.7 This factor,
combined with the
limited sample size and
assessment
duration (i.e., 1 hour,
which is shorter than
the extract’s reported
peak activity level(s)
of 1.5 to 4 hours;
see American Herbal
Pharmacopoeia, 200314)
may have negatively
impacted the results of
Warot’s9
study. Furthermore,
Nathan and colleagues13
utilized a small sample
of participants whose
mean age (x
= 58.46 years) was the
highest of all the acute
studies. They also
limited their assessment
duration to 90
minutes and administered
a lower (i.e., 120 mg),
versus higher, dose of a
GBE which, when these
factors
were combined, may have
interacted
synergistically to
contribute to the
study’s null findings.
Taken together, the
majority of studies that
have examined the acute
effects of GBE
administration in
healthy adults have
found the herbal
compound to be
efficacious in enhancing
certain aspects of
participants’
neuropsychological
functioning,
particularly
performances on tasks
assessing attention,
memory, and speed of
processing. While some
of these studies have
found the effects to be
dose and
time-dependent, though
not necessarily in a
linear fashion,
inconsistencies remain
among the acute
studies that have been
conducted to date. There
appears to be a trend,
however, among the
limited
number of acute studies
that have included
different doses of GBE
for positive
neuropsychological
effects to be more
closely associated with
higher doses of GBE
(i.e., > 240 mg) and/or
longer treatment/
assessment durations
(i.e., > 2.5 hours).
(The limited number of
acute studies that
included different
doses of GBE is n = 4;
i.e., if the Subhan &
Hindmarch7 and
Hindmarch8 studies
represent the same data
set.)
Short- to Long-Term
Studies
A total of 9 published
studies were found which
have examined the short-
to long-term
neuropsychological
effects of GBE/ginkgo in
healthy/cognitively
intact individuals.
(Short- to long-term
studies were defined as
the administration of
GBE to
healthy/cognitively
intact adults for a
minimum of
5 days and up to 2 or
more years.) Table 4
[download Table 4, pdf
file] on page 59
provides an overview
of these studies, which
are listed in
chronological order.
Table 2 provides
summaries of the
proprietary
GBE preparations and
Table 3 provides outcome
measures utilized in the
investigations (see
pages 56
and 57, respectively).
Mix & Crews15 conducted
the first known
double-blind,
fixed-dose,
placebo-controlled,
parallel-group
design study that
examined the short-term
(6 weeks) efficacy of
GBE (EGb 761A8) on the
neuropsychological
functioning of 48
generally healthy,
cognitively intact,
older adults (i.e., 55
to 86
years of age).
Participants in this
study were randomly
assigned to receive 180
mg/day of GBE or a
matching placebo, and
they completed a series
of neuropsychological
tests and measures both
at
pretreatment baseline
and again after 6 weeks
of treatment (i.e., just
prior to the termination
of the
regimen). (See Table 4
for a listing of the
specific tests
utilized.) The findings
from this trial revealed
that participants who
received 180 mg/day of
GBE (EGb 761A8) for 6
weeks exhibited
significantly
more improvement on a
task assessing speed of
processing abilities
(i.e., Stroop Color and
Word Test
Color-naming task) by
the end of treatment, as
compared to placebo
controls. Nonsignificant
trends
favoring improved
performances in the GBE
group were also
demonstrated on 3 of the
4 remaining
tasks that involved a
timed, speed of
processing component.
Furthermore, no
significant differences
were found between the
GBE and placebo groups’
change in performance
scores on any of the
verbal or
nonverbal/visual memory
measures included in the
study. However, a
nonsignificant trend,
favoring the
GBE group, was evident
by treatment end on the
Wechsler Memory
Scale-Revised Visual
Reproduction
I subtest. Additionally,
significantly more
participants in the GBE
group rated (via a
self-report
questionnaire) their
overall abilities to
remember by treatment
end as “improved,” as
compared to
placebo controls.
Similarly, Stough and
associates16
investigated the
neuropsychological
changes in 50 healthy
participants over a
30-day trial of 120
mg/day of GBE
[Blackmore’s Ginkgo
Biloba Forte,
Blackmore’s
Ltd., Balgowlah, NSW,
Australia] via a
randomized,
double-blind,
placebo-controlled
design.
Participants were
administered batteries
of neuropsychological
tests designed to assess
a diversity of
cognitive variables both
at pretreatment baseline
and again following the
30-day treatment phase
(see
Table 4 on page 59 for a
listing of the specific
tests utilized). The
results indicated that
the group
receiving the GBE
exhibited significant
improvements in speed of
information processing
(i.e., Working
Memory Speed), working
memory (i.e., Digit Span
Backwards), and memory
consolidation (i.e.,
over
the 30-minute delay
between presentations of
the Rey Auditory Verbal
Learning Test word list
trials).
Furthermore,
participants who were
classified in a “low,”
versus “high,” cognitive
ability group (via the
Wechsler Adult
Intelligence Scale-III
Vocabulary subtest
scores) exhibited
significantly improved
scores on the Trail
Making Test (Part A),
which the authors
attributed to the GBE. A
significant number
of positive subjective
effects were also
reported by the GBE,
versus the placebo,
group; namely,
subjective feelings of
cognitive clarity and
self-reported
improvements in memory
and attention.
Conversely, no
significant differences
were found for negative
side effects such as
headaches and nausea.
In another study,
Moulton and her
colleagues17 examined
the effects of 120
mg/day of Ginkgo biloba
[BioGinkgo 27/7, donated
by Pharmanex, Inc., a
division of NuSkin
International, Provo,
Utah] on the
memory processes of 60
healthy, young male
volunteers over 5
consecutive days via a
double-blind,
placebo-controlled,
between-subjects design.
On the fifth day of the
study, after obtaining
the GBE or
placebo treatment, a
series of cognitive
tests were administered
to participants (see
Table 4 for a listing
of the specific tests
utilized). Results
indicated that the group
receiving the GBE, as
compared to
placebo controls, failed
to demonstrate
significantly improved
performances on any of
the memory
measures. However, the
Wechsler Adult
Intelligence
Scale-Revised Digit Span
subtest results
approached significance,
with a higher mean score
observed in the GBE,
versus placebo, group.
The
authors acknowledged
that factors such as the
following may have
contributed to the
absence of
significant findings:
utilization of young
healthy participants,
limited dosage (120
mg/day) and treatment
regimen (5 days), and
the fact that baseline
assessments were not
administered to
participants to which
their performances at
the end of treatment
could have been
compared.
In an effort to expand
upon their previous
study 15 of GBE (EGb
761A8), Mix and Crews 18
published
the first known,
large-scale clinical
trial of the short-term
efficacy of GBE on the
neuropsychological
functioning of
cognitively intact older
adults (as assessed by
the Mini Mental State
Examination;
MMSE). Two-hundred and
sixty-two community
dwelling adults, 60
years of age and older,
who
reported no history of
dementia or significant
neurocognitive
impairments and obtained
MMSE scores
of at least 26, were
examined via a 6-week,
randomized,
double-blind,
fixed-dose,
placebo-controlled,
parallel-group design.
Participants were
randomly assigned to
receive either 180
mg/day of EGb 761A8
or a matching placebo
for 6 weeks and were
administered a series of
neuropsychological tests
and
measures at pretreatment
baseline and again after
6 weeks of treatment
(i.e., just prior to the
cessation of
the regimen). (See Table
4 for a listing of the
specific tests
utilized.) The primary
findings of the trial
indicated that, compared
to placebo controls,
participants who
received 180 mg/day of
EGb 761A8 for 6
weeks exhibited
significantly more
improvement on (1) tasks
(i.e., Selective
Reminding Test)
involving
delayed (30 minutes)
free recall and
recognition of
noncontextual,
auditory-verbal
material, and (2) a
task (i.e., Wechsler
Memory Scale-III, Faces
II subtest) assessing
delayed (30 minutes)
recognition of visual
material/human faces. It
should be noted,
however, that based on
the significant
difference found
between the 2 groups
pretreatment baseline
scores on this
particular visual/facial
memory task, this
result should be
interpreted with
caution. Additionally,
of the 13 total
neuropsychological
outcome/
efficacy variables
included in this study,
the GBE group exhibited
more improvement by
treatment end
on 11 of these measures
(includes both
significant and
nonsignificant results),
as compared to the
placebo group.
Supporting data for
these objective,
standardized,
neuropsychological
findings were
found via a subjective,
Follow-up Self-report
Questionnaire, in which
participants rated
changes in their
overall abilities to
remember from
pretreatment baseline to
6 weeks after the
initiation of treatment.
Specifically,
significantly more older
adults in the GBE group
rated their overall
abilities to remember
by treatment end as
“improved,” as compared
to placebo controls,
which was a consistent
finding with
the investigators’
previous smaller-scaled
GBE study.15 Taken
together, the results
from both the
objective, standardized
neuropsychological tests
and the subjective,
Follow-up Self-report
Questionnaire
utilized in this
large-scale trial18
provided complementary
evidence of the
potential efficacy of
relatively short-term (6
weeks) utilization of
GBE (EGb 761A8) in
enhancing certain
neuropsychological/memory
functions of cognitively
intact older adults, 60
years of age and over.
Approximately 6 weeks
after the online
publication of the Mix
and Crews large-scale
clinical trial,18 the
results of a clinical
trial conducted by
Solomon and his
colleagues19 were
published. This trial
reportedly involved a
6-week, randomized,
double-blind,
placebo-controlled,
parallel-group design
using
120 mg/day of Ginkgo
biloba extract
[GinkobaA8, Pharmaton,
Division of Boehringer
Ingelheim,
Ridgefield, CT.]. In
this trial, 230
generally healthy and
cognitively intact (as
assessed by the MMSE)
community-dwelling
adults between 60 and 82
years of age were
randomized in the study.
Participants
were administered a
series of
neuropsychological tests
and measures one day
prior to beginning the
GBE
or placebo treatment,
and again, within 3 days
of the end of the trial
(see Table 4 on page 59
for a listing
of the specific tests
utilized). Analysis of
both the modified
intent-to-treat sample
(n = 219) and the fully
evaluable sample, which
complied with the
treatment regimen and
returned for testing (n
= 203),
indicated no significant
differences between
treatment groups for any
of the outcome measures.
Furthermore, no
significant differences
were found between
participants in the GBE
and placebo groups
on a subjective,
self-report measure of
memory functioning or on
a global rating scale by
spouses,
relatives, and friends.
It should be noted,
however, that this study
has not been free from
controversy. In
particular, a diversity
of questions/concerns
and potentially
problematic issues have
been raised about
the study. These issues
include the following:
the reported utilization
of both placebo capsules
and GBE
tablets (that were
likely not similar in
appearance and which may
have compromised/not
maintained
blinding), questions
concerning the
appropriateness of the
lead investigator
(versus an independent
party) performing the
randomization of
participants, and the
apparent baseline
differences among
several
outcome measures that
were not accounted for
in their analyses (see
Arnold20 and Cott21 for
detailed
reviews). Such concerns
raise questions about
the validity of the
study’s overall findings
and
conclusions. [Despite
these potentially
confounding
methodological
questions, the reported
negative
outcomes of this trial
received more media
attention in the United
States than probably any
previous
clinical trial on
ginkgo. The general
message was that “ginkgo
does not work.” The
media apparently
failed to provide any
qualification that this
trial was performed on
healthy adults, which
distinguished it
from most of the trials
previously conducted on
cognitively impaired
subjects, most of which
reported
positive findings.
—Editor’s note] In
another study, Hartley
and his colleagues22
examined the effects of
GBE [Ginkyo One-A-Day
tablets, (LI 1370),
Lichtwer Pharma UK, Mere
Park, Marlow, Bucks, UK]
on cognition and mood in
34 healthy,
post-menopausal women
via a randomized,
double-blind,
placebo-controlled
design. The women were
administered a battery
of cognitive tests and
measures of mood and
menopausal symptoms at
baseline and again
following 7 days of
treatment (see Table 4
for a listing of the
specific tests
utilized). The results
of the investigation
revealed that the group
treated with the GBE, as
compared to placebo
controls, performed
significantly better on
a matching-to-sample
test of short-term
nonverbal memory, as
well as on a frontal
lobe task involving
mental flexibility/rule
shifting (i.e., IDED
test), and on a test
requiring sustained
attention and frontal
lobe functioning (i.e.,
PASAT). Alternatively,
no group effects
were found for the
women’s ratings of their
menopausal and bodily
symptoms, sleepiness,
aggression, or
mood. The authors noted
that these results
suggested that the
observed cognitive
benefits demonstrated
by the women in the GBE
group were unlikely due
to any of the assessed
menopausal/bodily
symptoms,
major mood changes, or
sleepiness.
Cieza and associates23
also investigated the
short-term (i.e., 28
days) efficacy of 240
mg/day GBE (EGb
761A8) on the “mental
functioning” of 66
healthy volunteers,
without age-associated
cognitive
impairment, via a
randomized,
double-blind,
fixed-dose,
placebo-controlled,
parallel-group,
monocentric
design. Participants
completed a series of
subjective measures
concerning their mental
and general
health and quality of
life, as well as a
diversity of tasks that
were based on a
neurobiologically based
classification of
functioning (see Table 4
on page 59 for a listing
of the specific tests
utilized), both at
baseline and at the end
of treatment (i.e., 28
days later). The results
of the study indicated
that GBE had
significant, positive
effects on participants’
self-estimated mental
health and quality of
life. The GBE,
versus placebo, group
also demonstrated
significantly better
action and reaction
motor performances (i.
e., Finger Tapping Test)
and judged their
subjective mood states
more positively during
the entire
treatment phase,
especially (and
significantly more)
after 2 weeks of
therapy.
Santos and colleagues24
appeared to have
reported the results of
the first long-term
(i.e., 8 months) study
of the efficacy of GBE
in 48 non-demented,
elderly men.
Specifically, the
investigation utilized a
doubleblind,
placebo-controlled,
independent group design
where participants
consumed either 80
mg/day of a GBE
[produced by Maze
Produtos Quimicos e
Farmaceuticos Ltda.] or
matching placebo for 8
months.
The men were evaluated
at baseline and
post-treatment via
Single Photon Emission
Computed
Tomography (SPECT)
scans, measures of blood
viscosity, and a
diversity of
neuropsychological tests
(see Table 4 for a
listing of the specific
tests utilized). By the
end of treatment, the
GBE group exhibited
increased cerebral
perfusion in several
areas corresponding to
bilateral frontal,
bilateral parietal,
right
frontal-parietal, left
temporal, and right
occipital brain regions,
as well as reduced blood
viscosity. In
contrast, the placebo
group displayed areas of
reduced cerebral
perfusion and higher
blood viscosity.
Furthermore, the GBE,
versus placebo, group
exhibited improvements
on the following: tests
of general
intelligence (e.g.,
WAIS-R Vocabulary,
Comprehension, and
Similarities subtests),
visuospatial abilities
(e.g., WAIS-R Block
Design and Object
Assembly subtests, Corsi
Blocks), attentional
processes (e.g.,
WAIS-R Digit Symbol,
Toulouse-Pieron
Concentrated Attention),
information processing
speed
(assessed via timed
tasks), enhanced verbal
memory (e.g., WMS-R
unrelated Verbal Paired
Associates), delayed
retrieval of visual
material (e.g., Rey-Osterrieth
Complex Figure Test),
fewer non-perseveration
errors per category on
the Wisconsin Card
Sorting Test, and fewer
word intrusion,
perseveration, and
repetition errors on a
verbal free recall task.
Persson and associates25
also examined the
utilization of
unspecified formulas of
ginkgo and ginseng in
healthy volunteers, as
compared to age and
education-matched
control groups that used
either no
nutritional supplements
or nutritional
supplements other than
ginkgo or ginseng. For
the purposes of this
paper, the data
involving participants
who utilized only
ginkgo, as compared to
controls, will be
reviewed. Participants,
who were free from
organic disease (such as
dementia) and scored 24
or greater
on the MMSE, were
selected from the Betula
Prospective Cohort
Study: Memory, Health,
and Aging
database (n = 3500) in
Sweden. Among the 40
individuals who
indicated current usage
of ginkgo at the
time of the study, 19
had been utilizing the
phytomedicinal compound
for 2 or more years,
while the
mean ginkgo intake time
for the remaining 21
individuals was 5.3
months. Participants
were evaluated at
only one time point on a
diversity of episodic
and semantic memory
tests and via
questionnaires
concerning individuals’
life style factors and
subjective memory
ratings (see Table 4 on
page 59 for a
listing of the specific
tests utilized). The
performances of the
individuals utilizing
ginkgo were then
compared to those
obtained by the 2
control groups. With the
exception of
significantly better
performances by Control
Group 2 (see Table 4 on
page 62 for inclusion
criteria), versus the
ginkgo
group, on a cued recall
task involving nouns
from sentences encoded
by verbal rehearsal, no
significant
group differences were
found for any of the
memory measures. As
noted by the authors,
however, this
study lacked direct
control of the dosage
and specificity of
ginkgo formulas utilized
and, thus, did not
report on the dosages or
types of ginkgo that
were used by
participants, nor their
overall levels of
compliance over time.
Furthermore,
participants were
evaluated at only one
time point. Such
concerns
raise questions about
the validity of the
study’s overall findings
and conclusions.
Summary of Short- to
Long-Term Studies
A total of 9 published
studies were found in
the literature that have
evaluated the short- to
long-term
neuropsychological
effects of GBE (and
unspecified preparations
of ginkgo in one
study25) in healthy/
cognitively intact
adults. (Short- to
long-term studies were
defined as the
administration of GBE to
healthy/cognitively
intact adults for a
minimum of 5 days and up
to 2 or more years.)
The number of
participants enrolled in
these studies ranged
from a low of 3422 to a
high of 262.18 Three
investigations15,16,23
utilized relatively
similar numbers of male
and female participants,
while 3 other
studies18,19,25 included
notably more (i.e., n >
20) females than males.
Two additional trials17,
24
included only males,
while 1 study22 assessed
only females. With the
exception of 2
investigations16,17
where the mean age of
participants fell below
31 years, the remaining
short- to long-term
studies of
ginkgo involved
participants whose mean
ages were greater than
55 years. In contrast to
the acute
studies, 5 of the short-
to long-term
trials15,18,19,24,25
included an objective
measure to assess
participants’ levels of
cognitive intactness
(and specified inclusion
criteria scores), while
1 study
denoted that
participants were
without “age-associated
cognitive impairment”
(as judged by Cognitive
Minimal Screening).23
The remaining 3
studies16,17,22
indicated only that they
included “healthy”
participants.
All but one
investigation25 utilized
double-blind,
placebo-controlled
designs. The duration of
the shortto
long-term studies’ GBE/ginkgo
treatments ranged from 5
days17 to 2-plus
years.25 In addition to
a
placebo, treatments
involved the
administration of
various GBEs/ginkgo
treatments that were
identified
as follows:
• Ginkgo biloba extract
EGb 761®,
• Blackmore’s Ginkgo
Biloba Forte,
• BioGinkgo 27/7,
• Ginkoba®, Ginkyo
One-A-Day (LI 1370),
• A GBE that was only
cited as having been
produced by Maze
Produtos Quimicos e
Farmaceuticos Ltda. and
prepared by Magister
Medicamentos, Ltda., and
• Unspecified
preparations of ginkgo
in one study.25
The daily doses of GBE
in these trials ranged
from a low of 80 mg24 to
a high of 240 mg.23 It
should be
noted that in one
additional study,25 the
formula(s) and dose(s)
of ginkgo were
unspecified and
participants’ levels of
compliance with the
treatment regimen(s)
were not monitored.
A wide array of outcome
measures, assessing a
diversity of
neuropsychological
processes, were
administered in the
short- to long-term
studies. These ranged
from standardized and
objective
neuropsychological tests
that are frequently
utilized in clinical
practice, to
author-generated,
subjective,
self-report
questionnaires and
surveys of caregiver’s
impressions of global
change.
Significant, positive
effects of GBE/ginkgo
were found in 6 out of 9
short- to long-term
studies.
Specifically, a dose of
80 mg/day of a GBE
administered for 8
months was shown to
increase cerebral
perfusion in various
brain regions and result
in a significant
reduction in blood
viscosity, as compared
to
placebo.24 Participants
who received this GBE
treatment also performed
significantly better
than
controls on several
verbal and performance
subtests of the WAIS-R,
on 2 subtests from the
WMS-R, and
on 3 additional
retrieval tasks. In
addition, the GBE group
exhibited fewer non-perseverative
errors per
category on the WCST and
significantly more
cancellations and fewer
errors on a test
assessing
concentrated attention,
as well as fewer word
intrusion,
perseveration, and
repetition errors on a
verbal
free recall task, as
compared to placebo
controls.
Doses of 120 mg/day of
GBE were utilized in 4
of the short- to
long-term studies.16,
17, 19, 22 In one
trial,22 after 7 days of
120 mg/day of a GBE, the
treatment group, versus
placebo controls,
displayed significantly
better short-term verbal
memory on the Digit
Matching-to-Sample Test
and enhanced
performances on tasks
involving rule shifting
(i.e., IDED task) and
sustained attention
(i.e., PASAT).
Stough and associates16
also found significant
neurocognitive
improvements in
participants who
received 120 mg/day of a
GBE for 30 days, as
compared to placebo
controls, on a backwards
digit span
task, in working memory
speed, and on an
auditory verbal learning
delayed recall task.
Improved
performances on a task
involving sequencing and
psychomotor speed (i.e.,
TMT, Part A) were also
noted in a low, versus
high, cognitive ability
group that received the
extract. Furthermore,
the GBE,
versus placebo, group
self-reported
significantly more
feelings of clarity and
improvements in memory
and attention.
The Mix and Crews
research group has
conducted 2 clinical
trials15,18 that
examined the
neuropsychological
efficacy of 180 mg/day
of a GBE for 6 weeks.
Results of these studies
revealed that
older, cognitively
intact participants who
received the
phytomedicinal extract
for 6 weeks exhibited
significantly more
improvement on
standardized
neuropsychological tests
assessing speed of
processing
abilities,15 delayed
free recall and
recognition of
auditory-verbal
material,18 and delayed
recognition of
visual material,18 as
compared to placebo
controls. Furthermore,
in both studies
significantly more older
adults who received the
GBE, versus a placebo,
rated their overall
abilities to remember by
treatment
end as “improved.”
Another short- to
long-term study examined
the effectiveness of 240
mg/day of a GBE
administered for
28 days.23 Participants
in the GBE group
exhibited superior
performances on a motor
task (i.e., Finger
Tapping Test) measuring
both action and reaction
functions, and they
self-rated their levels
of mental
health and quality of
life higher and judged
their mood states more
positively during the
treatment phase,
as compared to the
controls.
In contrast, 3 short- to
long-term
studies17,19,25 failed
to find significant
positive results for
formulas of
GBE or unspecified
ginkgo preparations. As
noted earlier, in at
least 2 of these
investigations, which
utilized either 120
mg/day dose of a GBE for
6 weeks19 or unspecified
formulas and doses of
ginkgo
products for up to
2-plus years,25
questions/concerns have
been raised about the
soundness of their
methodologies and
validity of their
findings. Furthermore,
the third
investigation17 with
null results
utilized the youngest
sample of participants
(i.e., x < 21.0 years),
the shortest
treatment/assessment
duration (i.e., 5 days)
of any of the short- to
long-term studies, and
did not conduct baseline
cognitive/
memory assessments,
which may have
contributed to the
reported negative
findings in this study.
Overall, the majority of
investigations that have
examined the short- to
long-term effects of GBE/ginkgo
in healthy/cognitively
intact persons have
found the herbal product
to improve certain
neuropsychological
processes, especially
performances on tasks
assessing aspects of
memory, attention,
and speed of processing
abilities. Four of the
short-term studies also
bolstered their
objective
neurocognitive test
findings with
self-report data, as
compared to placebo
controls. In 2 of these
studies,15,18
significantly more
participants who
received GBE rated their
overall abilities to
remember
by treatment end as
improved. In the third
study,16 participants
reported significantly
more feelings of
clarity and improvements
in memory and attention.
In the fourth study, 23
participants rated their
levels of mental health
and quality of life
significantly higher,
and they judged their
mood states more
positively during
treatment.
Conclusions and
Directions for Future
Research
Taken together, a total
of 16 published studies
were found in the
scientific literature
(through September
2004) which have
examined the acute or
short- to long-term
neuropsychological
efficacy of GBE (and
unspecified preparations
of ginkgo in one
study25) in healthy and
cognitively intact
adults. Significant
positive results for
formulas of GBE were
found in 11 out of 16
studies (10 of 15
studies if the Subhan
& Hindmarch7 and
Hindmarch8 studies
represent the same
investigation). Although
inconsistencies exist
in this limited body of
research, some of the
most common positive
neuropsychological
effects found for
GBE across the acute and
short- to long-term
studies involving
healthy/cognitively
intact participants
have been enhanced
performances on tasks
assessing aspects of
memory, attention, and
speed of
processing abilities.
Furthermore, as cited
earlier, complementary
subjective/self-report
evidence to
support the findings
from the objective
neurocognitive tests has
been provided in four of
the short- to
long-term studies that
included such measures.
However, this review of
the scientific
literature on acute and
short- to long-term
studies has also
revealed a diversity of
findings across these
investigations. Based on
these findings and the
array of
ginkgo product
formulations, doses,
treatments/assessment
durations, and outcome
measures utilized, as
well as the
methodological
limitations of some of
the investigations
(e.g., limited sample
sizes, young
ages of participants),
future well-designed
trials are required to
precisely identify the
optimum dose(s),
type(s)/formula(s) of
ginkgo product(s), and
treatment regimen(s).
These kinds of trials
will maximize
the likelihood of
obtaining certain
neurocognitive/neuropsychological
benefits in particular
groups of
healthy/cognitively
intact adults (e.g., of
varying ages and
genders). Specifically,
large-scale
investigations (both
acute and short-term)
are needed, especially
with healthy/cognitively
intact middleaged
and older adults who
often complain of
(age-related)
memory/cognitive
difficulties, that
compare
and contrast different
formulas, dosage
regimens, and
treatment/assessment
durations of GBE in
healthy/
cognitively intact males
and females from various
age groups. These
clinical trials should
utilize
rigorous
methodology/designs, and
precisely define and
assess their medical and
neuropsychological
inclusionary/exclusionary
criteria (e.g., via
objective measures of
cognitive intactness).
Outcome
measures should be
carefully selected to
ensure that they have
been documented to be
reliable, valid,
and sensitive measures
of particular
neuropsychological
processes, and that they
decrease the possibility
of familiarity/practice
effects over successive
administrations (e.g.,
alternate forms).
Furthermore,
methodologically sound,
longitudinal, clinical
trials are also needed
that examine the
neuropsychological
efficacy of GBE(s) over
periods of several
months to years to
ascertain if additional
neuropsychological
benefits/effects become
evident and/or if the
phytomedicinal compound
demonstrates long-term
neuroprotective
properties.
Authors’ Biographical
Sketches
W. David Crews, Jr.,
PhD: Dr. Crews is a
licensed clinical
neuropsychologist,
President of Virginia
Neuropsychology
Associates, Inc. and
CogniCheck, Inc. (www.CogniCheck.com)
and an Adjunct
Assistant Professor in
the Department of
Psychology at Virginia
Polytechnic Institute
and State
University. He has
authored/co-authored
over 50 peer-reviewed
publications in clinical
neuropsychology,
behavioral medicine, and
the neuropsychological
effects of herbal
compounds. He has
been awarded Diplomate
status through the
American Board of
Psychological
Specialties
(Neuropsychology) and
the American Board of
Disability Analysts and
was elected as a Fellow
by the
National Academy of
Neuropsychology.
David W. Harrison, PhD:
Dr. Harrison is a
licensed clinical
neuropsychologist and an
Associate
Professor and Director
of the Neuropsychology
Laboratory in the
Department of Psychology
at Virginia
Polytechnic Institute
and State University. He
has authored/co-authored
over 150 peer-reviewed
publications in clinical
neuropsychology and
behavioral/cognitive
neuroscience. He has
been awarded
Diplomate status through
the American Board of
Psychological
Specialties
(Neuropsychology),
American Board of
Disability Analysts,
Neurotherapy
Certification Board,
American Board of
Forensic
Examiners, and the
American Board of
Vocational
Neuropsychology and was
elected as a Fellow by
the
National Academy of
Neuropsychology.
Melanie L. Griffin: Ms.
Griffin obtained her
Bachelor of Science
degree in Psychology
from Virginia
Polytechnic Institute
and State University and
is currently a graduate
student at Southeastern
Louisiana
University. Upon her
graduation at Virginia
Tech, she received the
Department of
Psychology’s
Outstanding
Undergraduate of the
Year and Undergraduate
Researcher of the Year
awards for 2004. She
has also served as the
clinical research
coordinator on a
grant-funded trial that
examined the
neuropsychological
efficacy of cranberry
juice.
Katherine D. Falwell:
Ms. Falwell obtained her
Master of Arts degree in
Clinical and Community
Psychology from the
University of North
Carolina-Charlotte and a
Post-Graduate
Certificate in Applied
Behavior Analysis from
George Mason University.
She is currently
completing her PhD in
Clinical
Psychology at the
Fielding Graduate
Institute and is
employed as a
psychologist at the
Central Virginia
Training Center.
Tara Crist: Ms. Crist is
currently pursuing her
Bachelor of Science
degree in Psychology at
Virginia
Polytechnic Institute
and State University,
where she also serves as
a research associate in
the
Neuropsychology
Laboratory.
Lesley Longest: Ms.
Longest is currently
pursuing her Bachelor of
Science degree in
Psychology at
Virginia Polytechnic
Institute and State
University, where she
also serves as a
research associate in
the
Neuropsychology
Laboratory.
Laura Hehemann: Ms.
Hehmann obtained her
Bachelor of Science
degree in Psychology at
Virginia
Polytechnic Institute
and State University and
is currently a graduate
student at Radford
University.
Stephenie T. Rey, OTR/L:
Ms. Rey obtained her
Master of Science degree
in Occupational Therapy
from Rush
Presbyterian-St. Lukes
Medical Center/School
and is currently a
registered and licensed
Occupational Therapist.
She also currently
serves as a research
associate with Virginia
Neuropsychology
Associates, Inc.
Address correspondence
to W. David Crews, Jr.,
PhD,
Virginia Neuropsychology
Associates, Inc., P.O.
Box 11754, Lynchburg,
Virginia 24506;
telephone:
434-942-9325; e-mail:
wdcrewsjr@aol.com..
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