ARTICLE IN PRESS

JNS-10913; No of Pages 6
Journal of the Neurological Sciences xxx (2009) xxx–xxx

Contents lists available at ScienceDirect

Journal of the Neurological Sciences

j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s

Efficacy and tolerability of Ginkgo biloba extract EGb 761® by type of dementia:
Analyses of a randomised controlled trial
Oleksandr Napryeyenko a, Grigoriy Sonnik b, Igor Tartakovsky c,⁎
a
Psychiatry, National Medical University, Kyiv City Clinical Psychoneurological Hospital No. 1, 103 A, Frunze Str., Kyiv 04080, Ukraine
b
Psychiatry, Narcology and Medical Psychology Faculty, Poltava Regional Psychoneurological Dispensary, 3, Zygina Str., Poltava 36037, Ukraine
c
Clinical Research Department, Dr. Willmar Schwabe GmbH & Co. KG, Willmar-Schwabe-Str. 4, 76227 Karlsruhe, Germany

a r t i c l e i n f o a b s t r a c t

Available online xxxx Secondary analyses of a randomised controlled trial were performed to find out whether treatment effects of
Ginkgo biloba extract EGb 761® differed by type of dementia. Three hundred ninety-five patients aged 50 years
Keywords: or above, with dementia with neuropsychiatric features were treated with EGb 761® (240 mg/day) or placebo
Ginkgo biloba extract
for 22 weeks. Patients scored between 9 and 23 on the Short Syndrome Test (SKT), a cross-culturally validated
EGb 761®
cognitive test battery. Their total score on the Neuropsychiatric Inventory (NPI) was at least 5. Efficacy was
Dementia
Alzheimer's disease
assessed by the SKT test battery (primary outcome measure), the Verbal Fluency Test, the Clock-Drawing Test,
Vascular dementia the NPI, the Hamilton Rating Scale for Depression (HAMD), and the Gottfries–Bråne–Steen Scale (GBS).
Randomised controlled trial Applying standard research diagnostic criteria 214 patients were diagnosed with Alzheimer's disease
Neuropsychiatric symptoms (probable AD or possible AD with cerebrovascular disease) and 181 with probable vascular dementia (VaD).
Under EGb 761® treatment the SKT total score improved by − 3.0 ± 2.3 and − 3.4 ± 2.3 points in patients with
AD and VaD, respectively, whereas the patients on placebo deteriorated by + 1.2 ± 2.5 and + 1.5 ± 2.2 points,
respectively (p b 0.01 for both drug–placebo differences). Significant drug–placebo differences were found for
all secondary outcome variables with no major differences between AD and VaD subgroups. The rate of adverse
events tended to be higher for the placebo group.
© 2009 Elsevier B.V. All rights reserved.

1. Introduction To assess the efficacy of EGb 761® by type of dementia, separate

analyses were performed for the AD and VaD subgroups as specified
The Ginkgo biloba extract EGb 761® has been tested for efficacy in prospectively in the protocol of the clinical trial published recently by
dementia in a series of clinical trials which have demonstrated its Napryeyenko et al. [3].
beneficial effects on cognitive performance, activities of daily living
and behavioural symptoms of dementia [1–3]. Comprising effects on
2. Methods
blood viscosity and perfusion [4], oxidative stress and mitochondrial
function [5,6], insulin resistance [7], formation and toxicity of Aβ
The trial was carried out in accordance with the Declaration of
oligomers [8,9] as well as on neurotransmitter systems [10,11] the
Helsinki (year 2000 revision), the harmonised tripartite guideline for
pharmacodynamic profile of EGb 761® does not appear to be specific
good clinical practice (GCP) issued by the International Conference on
for one certain type of dementia. Moreover, former clinical trials
Harmonisation (ICH) [23] and applicable local laws. The protocol was
suggest that the drug has beneficial effects in Alzheimer's disease
approved by the ethics committee of the State Pharmacology Center at
(AD) and vascular dementia (VaD) [12,13]. Taking this into account,
the Ukraine Ministry of Health. At a start-up meeting investigators
both patients with AD and patients with VaD were enrolled in a
and clinical staff involved in the trial were trained in legal
recently conducted randomised controlled trial [3]. Considering
requirements and GCP standards by experts in GCP and clinical trials
further that AD and VaD have a number of risk factors in common
methodology, all with long-standing experience in their fields.
[14–17], that clinico-pathological studies have shown a high coin-
Informed consent was elicited from all patients before enrolment.
cidence of AD-specific and vascular pathology [18,19], that cerebro-
vascular lesions contribute to cognitive and functional deterioration
in AD [18,20], and that therefore mixed pathology may underlie a 2.1. Participants
considerable proportion of dementia cases [21,22], this type of trial
appears to be justified. Four hundred outpatients were recruited at outpatient clinics of 16
psychiatric or neurological hospitals. They were eligible for this study
⁎ Corresponding author. Fax: +49 721 4005 8545. if they were at least 50 years of age and diagnosed with AD (probable
E-mail address: Igor.Tartakovsky@schwabe.de (I. Tartakovsky). AD or possible AD with cerebrovascular disease) or VaD. Clinical

0022-510X/$ – see front matter © 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jns.2009.02.353

Please cite this article as: Napryeyenko O, et al, Efficacy and tolerability of Ginkgo biloba extract EGb 761® by type of dementia: Analyses of a
randomised controlled trial, J Neurol Sci (2009), doi:10.1016/j.jns.2009.02.353
 ARTICLE IN PRESS
2 O. Napryeyenko et al. / Journal of the Neurological Sciences xxx (2009) xxx–xxx
diagnoses were established employing the criteria specified by the
National Institute for Neurological and Communicative Disorders and
Stroke (NINCDS) together with the Alzheimer's Disease and Related
Disorders Association (ADRDA) [24] and by the National Institute of
Neurological Disorders and Stroke (NINDS) together with the
Association Internationale pour la Recherche et l'Enseignement en
Neurosciences (AIREN) [25] as appropriate. A CT or MRI scan, no more
than one year old, had to be consistent with the inclusion diagnosis.
The Test for Early Detection of Dementia with Discrimination from
Depression (TE4D) [26] was used as a screening instrument and to
verify the presence of cognitive impairment in at least two domains. It
was preferred to the Mini-Mental State Examination (MMSE) because
of its higher sensitivity and specificity to discriminate between
demented and non-demented subjects [26,27]. A total cognitive
score of no more than 35 was required for inclusion. Patients had to
have mild to moderate dementia as evidenced by a total score from 9
to 23 (both inclusive) on the SKT test battery [28], which roughly
corresponds to a range from 14 to 25 on the MMSE or 17 to 35 on the
cognitive subscale of the Alzheimer's Disease Assessment Scale
(ADAS-cog) [29]. The Clock-Drawing Test (CDT) after Sunderland
et al. [30] was employed as a second screening instrument, the score
of which had to be below 6. Patients had to score at least 5 on the 12-
item Neuropsychiatric Inventory (NPI) [31], with at least one item
score (other than delusions or hallucinations) being 3 or higher.
Severe depression was excluded by requiring a score below 20 on the
17-item Hamilton Rating Scale for Depression (HAMD) [32]. The
presence of a caregiver was required who was able and willing to
provide information on the patient's behaviour and competence to
perform activities of daily living.
Patients were excluded from the study, if they had any other type
of dementia or neurological disorder, current or recent major
depression or other psychiatric disorder, severe or insufficiently
controlled cardiovascular, renal, or hepatic disorder, diabetes, anae-
mia, or thyroid dysfunction. Active malignant disease, HIV or lues
infection and gastrointestinal diseases with uncertain absorption
were not accepted. Treatment with other anti-dementia drugs,
cognitive enhancers, cholinergic, anti-cholinergic or haemorheologi-
cally active drugs, anti-Parkinson drugs or Ginkgo supplements was
prohibited during the study and at least 8 weeks preceding
randomisation.
2.2. Trial design and intervention
The multi-centre trial with two parallel treatment arms was
carried out in a double-blind manner. After a medication-free
Fig. 1. Disposition of patients; a) adverse event (1), withdrawal of consent (1); b) withdrawal of consent (2); c) withdrawal of consent (1); d) lost to follow-up (1), withdrawal of
consent (1); e) withdrawn due to medical reasons (1), withdrawal of consent (1).
Please cite this article as: Napryeyenko O, et al, Efficacy and tolerability of Ginkgo biloba extract EGb 761® by type of dementia: Analyses of a
randomised controlled trial, J Neurol Sci (2009), doi:10.1016/j.jns.2009.02.353
screening period of up to 4 weeks, patients were randomly assigned
to receive the Ginkgo biloba extract EGb 761® at a daily dose of 240 mg
(2 × 120 mg) or placebo. Centre-stratified randomisation (drug–
placebo ratio 1:1) in blocks of four was performed by the sponsor's
biometrics unit using a validated computer program that linked
ascending drug numbers to active drug or placebo, respectively. The
randomisation list was sealed and stored safely at the sponsor's
biometrics unit, and block length was not disclosed to investigators.
Drug and placebo tablets were indistinguishable by appearance,
packaging and labelling. After the baseline assessment, each patient
was allocated the drug package with the lowest drug number still
available at the clinical site. The investigational product, EGb 761® is a
dry extract from Ginkgo biloba leaves (35–67:1), extraction solvent:
acetone 60% (w/w). The extract is adjusted to 22.0–27.0% Ginkgo
flavonoids, calculated as Ginkgo flavone glycosides, and 5.0–7.0%
terpene lactones consisting of 2.8–3.4% ginkgolides A, B, C and 2.6–
3.2% bilobalide, with a content of ginkgolic acids below 5 ppm. Drug
and placebo were manufactured and provided by Dr. Willmar
Schwabe GmbH & Co. KG, Karlsruhe, Germany.
2.3. Outcome measures
The SKT, a 9-item cognitive test battery with scores ranging from
0–27 (higher scores indicating more severe impairment) was defined
as primary efficacy measure. Secondary efficacy measures were the
12-item NPI, which assesses frequency and severity of neuropsychia-
tric symptoms (composite score range 0–144) and caregiver distress
caused by such symptoms (score range 0–60); the activities-of-daily-
living (ADL) subscale of the Gottfries–Bråne–Steen (GBS) overall
geriatric assessment scale [33]; the total score of the GBS (comprised
by the intellectual “I”, the emotional “E”, and ADL subscores, but not
the behavioural “S” subscore which was not documented to avoid
redundancy); the Verbal Fluency Test (animal fluency) [34]; the CDT
and the HAMD. Patient self-ratings of presence and severity of
dizziness and tinnitus, symptoms often associated with old age, were
documented using 11-point box scales, 0 representing absence and 10
indicating extreme severity of a symptom. Investigators and investi-
gational staff were trained in the administration of tests and scales by
an experienced geriatric psychiatrist and neuropsychologist, using
original test material and video presentation. Safety was assessed by
documentation of adverse events, physical examination, electrocar-
diography, and laboratory tests. All assessments were performed at
baseline, week 12 and week 22 (except adverse events, which were
also asked for at week 6 and week 17 phone calls, and the other safety
variables, that were only assessed at baseline and week 22).
 ARTICLE IN PRESS
O. Napryeyenko et al. / Journal of the Neurological Sciences xxx (2009) xxx–xxx 3

Table 1
Demographic data and baseline characteristics (FAS; numbers and percentages for gender, means ± sd for all other data; two-sided p-values for the Chi-squared test (gender) or
the t-test (other))

AD VaD
EGb 761® Placebo p-value EGb 761® Placebo p-value
(n = 104) (n = 110) (n = 94) (n = 87)
Gender m 34(33%) 32(29%) 0.57 21(22%) 23(26%) 0.52
f 70 (67%) 78 (71%) 73 (78%) 64 (74%)
Age (years) 66 ± 8 64 ± 8 0.10 63 ± 8 63 ± 9 0.66
Height (cm) 168 ± 8 168 ± 8 0.62 166 ± 7 166 ± 9 0.90
Weight (kg) 73 ± 11 72 ± 11 0.61 75 ± 12 74 ± 10 0.68
SKT total score 16.4 ± 3.8 15.8 ± 3.8 0.24 14.8 ± 3.8 15.0 ± 3.6 0.71
NPI composite 19.6 ± 8.4 20.1 ± 8.6 0.64 23.2 ± 10.4 23.6 ± 11.2 0.82
NPI distress 12.4 ± 6.6 12.5 ± 6.2 0.89 14.6 ± 6.5 14.4 ± 6.7 0.82
GBS-ADL 4.3 ± 4.0 4.1 ± 4.0 0.75 5.4 ± 3.7 5.9 ± 4.1 0.43
GBS total 36.2 ± 10.6 34.2 ± 8.9 0.14 34.4 ± 7.0 34.4 ± 8.4 0.995
CDT 4.5 ± 0.6 4.5 ± 0.6 0.82 4.6 ± 0.6 4.6 ± 0.5 0.50
Verbal fluency 7.2 ± 2.0 7.4 ± 1.9 0.44 6.8 ± 1.9 6.7 ± 2.1 0.77
CSS dizziness 3.1 ± 2.3 3.0 ± 2.2 0.76 3.5 ± 2.2 3.8 ± 2.0 0.29
CSS tinnitus 2.0 ± 2.4 1.7 ± 2.2 0.43 2.2 ± 2.3 2.5 ± 2.2 0.40

2.4. Statistical analyses
The primary aim of the study was to confirm the efficacy of EGb
761® in patients suffering from dementia (AD or VaD) with
neuropsychiatric symptoms. A secondary aim was to investigate the
efficacy of EGb 761® in the two diagnostic subgroups. The change from
baseline to week 22 in the SKT total score was specified as primary
target variable. The confirmatory analysis of the main target variable
within the total sample and the calculation of sample size is described
elsewhere [3]. Consistent treatment response, as defined by an
improvement in the SKT total score by at least 3 points together
with no deterioration in both the NPI composite and the ADL subscore
of the GBS was considered an important secondary outcome variable.
The analyses of efficacy within the subgroups defined by type of
dementia were performed descriptively using two-sided t-tests. The
primary efficacy analysis was based on the full analysis set (FAS)
which included a) all randomised patients who received at least one
dose of the study drug and had an SKT after baseline, and b) all
randomised patients having received at least one dose of the study
drug who had discontinued prematurely due to an adverse event
possibly related to the drug under study regardless of an SKT rating
after baseline. Missing values were substituted for by carrying forward
the last observed value (LOCF) as recommended by the Division of
Neuropharmacological Drug Products (DNDP). A per-protocol analysis
including only patients without any relevant protocol violation was
performed in addition. Safety parameters were analysed in the safety
set (SAF) including all randomised patients having received at least
one dose of study drug.
3. Results
The main results for efficacy and safety were published elsewhere
[3]. In the following sections results are reported for a priori specified
analyses of subgroups by type of dementia.
3.1. Patient sample
Informed consent was elicited from all patients before any trial-
related procedures were undertaken. Of the 400 patients randomised,
218 had AD (either probable AD or possible AD with cerebrovascular
disease) and 182 were diagnosed with probable VaD. Patient
disposition is depicted in Fig. 1. All patients received treatment in
accordance with their random allocation and were thus included in
the safety analysis set (SAF). Dropout rates were low and the
apparently higher attrition from the AD group under placebo may
be a matter of chance. The FAS for intent-to-treat analysis was
comprised of 214 patients with AD and 181 patients with VaD.
Demographic data and baseline characteristics are shown in Table 1.
Within each diagnostic sub-sample drug and placebo groups were
well comparable with respect to demographics and baseline char-
acteristics. Patients with AD tended to have marginally more cognitive
impairment, whereas neuropsychiatric features and neurosensory
symptoms tended to be slightly more pronounced in VaD patients.

Table 2
Changes from baseline to week 22 on the primary (SKT) and secondary outcome measures
(FAS; means± sd and two-sided p-values of the t-test)
Table 3
AD VaD Response rates for SKT (at least 3 points), NPI composite (at least 4 points), GBS-ADL (any
EGb 761® Placebo p-value EGb 761® Placebo p-value improvement), and consistent response (at least 3 points improvement in the SKT and no
(n = 104) (n = 110) (n = 94) (n = 87) worsening on both NPI and GBS-ADL) (FAS; numbers (percent) and two-sided p-values of
SKT total score −3.0 ± 2.3 +1.2 ± 2.5 b 0.01 −3.4 ± 2.3 +1.5 ± 2.2 b0.01 the Chi-squared test)
NPI composite −6.2 ± 5.0 +2.2 ± 5.0 b 0.01 −7.0 ± 5.1 + 2.8 ± 6.1 b0.01
AD VaD
NPI distress −4.4 ± 4.6 +0.4 ± 3.2 b 0.01 −5.2 ± 4.1 + 0.8 ± 3.8 b0.01
GBS-ADL −1.6 ± 2.7 +0.8 ± 2.1 b 0.01 − 2.2 ± 2.7 +1.0 ± 2.9 b0.01 EGb 761® Placebo p-value EGb 761® Placebo p-value
GBS total − 9.1 ± 8.8 +3.5 ± 7.4 b 0.01 − 10.8 ± 8.4 + 4.8 ± 8.8 b0.01 (n = 104) (n = 110) (n = 94) (n = 87)
CDT + 1.3 ± 1.4 +0.0 ± 0.8 b 0.01 + 1.0 ± 1.1 − 0.1 ± 0.6 b0.01 SKT 67(64%) 7(6%) b0.01 63(67%) 5(6%) b0.01
Verbal fluency + 1.5 ± 1.6 −0.8 ± 1.5 b 0.01 + 1.5 ± 1.5 − 0.8 ± 1.4 b0.01 NPI composite 75(72%) 6(5%) b0.01 74(79%) 8(9%) b0.01
CSS dizziness −1.5 ± 1.6 − 0.4 ± 1.1 b 0.01 −1.9 ± 1.7 − 0.2 ± 1.2 b0.01 GBS-ADL 56(54%) 20(18%) b0.01 65(69%) 9(10%) b0.01
CSS tinnitus − 0.7 ± 1.4 − 0.0 ± 0.8 b 0.01 −1.5 ± 1.8 − 0.0 ± 0.9 b0.01 Consistent response 64(62%) 4(4%) b0.01 62(66%) 5(6%) b0.01

Please cite this article as: Napryeyenko O, et al, Efficacy and tolerability of Ginkgo biloba extract EGb 761® by type of dementia: Analyses of a
randomised controlled trial, J Neurol Sci (2009), doi:10.1016/j.jns.2009.02.353
 ARTICLE IN PRESS
4 O. Napryeyenko et al. / Journal of the Neurological Sciences xxx (2009) xxx–xxx

Fig. 2. Changes from baseline of SKT total scores (means, sd) by type of dementia.

3.2. Efficacy
Patients with either type of dementia improved in the primary and
all secondary outcome measures under EGb 761®, whereas those who
received placebo deteriorated further or remained stable at best.
Details are shown in Table 2. Rates of clinically meaningful response
are provided in Table 3. Changes from baseline as well as response
rates are essentially similar for AD and VaD subgroups, with a slight
tendency towards better outcomes in VaD patients. For the primary
and the two most important secondary outcome measures the
development of treatment effects over time is depicted in Figs. 2–4.
were observed in 82 (93%) patients taking placebo. AEs occurring in at
least one of the subgroups, either under EGb 761® or under placebo, at
a frequency of 5% or higher are listed in Table 4. In the AD subgroup
there were 2 serious AEs (SAEs) in 2 (2%) patients treated with EGb
761® and 4 SAEs in 4 (4%) patients receiving placebo. In the VaD
subgroup 5 SAEs were reported for 5 (5%) patients of the EGb 761®
group and 9 SAEs were documented for 7 (8%) patients of the placebo
group. A causal relationship with the drug under study could be ruled
out for all SAEs. All SAEs are listed in Table 4. Laboratory tests,
electrocardiography, physical examinations and vital signs did not
reveal any risk of EGb 761® in any of the aetiological subgroups.

3.3. Safety 4. Discussion

In the AD subgroup 142 adverse events (AEs) were observed in 80 Like the confirmatory analysis based on the data of the whole
(75%) patients treated with EGb 761® and 230 AEs were documented sample, which was discussed elsewhere [3], descriptive subgroup
for 96 (86%) patients receiving placebo. In the VaD subgroup 160 AEs analyses showed significant superiority of EGb 761® over placebo in
were reported for 86 (91%) patients taking EGb 761® and 251 AEs both types of dementia. For AD and VaD patients the clinical significance

Fig. 3. Changes from baseline of NPI composite score (means, sd) by type of dementia.

Please cite this article as: Napryeyenko O, et al, Efficacy and tolerability of Ginkgo biloba extract EGb 761® by type of dementia: Analyses of a
randomised controlled trial, J Neurol Sci (2009), doi:10.1016/j.jns.2009.02.353
 ARTICLE IN PRESS
O. Napryeyenko et al. / Journal of the Neurological Sciences xxx (2009) xxx–xxx 5

Fig. 4. Changes from baseline of GBS-ADL subscore (means, sd) by type of dementia.

of the cognitive effects could be demonstrated by improvements in This trial differs from previous trials of EGb 761® in that the
neuropsychiatric symptoms, caregiver distress related to such symp- patients were required to have neuropsychiatric symptoms of
toms, patients' ability to cope with the demands of daily life, and overall dementia in addition to their cognitive deficits. This could raise
assessment. These findings are not unexpected, taking into account that questions with regard to external validity. Considering however that
former studies have demonstrated efficacy of EGb 761® in AD [35–37], up to 80% of patients with dementia, irrespective of the aetiological
AD with neuropsychiatric features [38], VaD [39], and in mixed samples type, exhibit such symptoms [40], requiring their presence certainly
of patients with AD or VaD [12,13]. leads to a much more representative sample than requiring their
The sample size of the present study was large enough to permit absence as in some trials with other anti-dementia agents [41].
separate statistical analyses not only for the AD patients, but also for Moreover, admitting patients with possible AD associated with
those with VaD. The proportion of patients with VaD was higher than cerebrovascular disease rather than only patients with probable AD
in similar trials carried out in Germany and the USA [12,13], which reflects more accurately the clinical reality with a considerable
may be explained by less rigorous treatment of cardiovascular risk proportion of patients actually having both pathologies [18,19].
factors, in particular hypertension, in Ukraine due to economical Although NPI baseline scores appeared to be slightly higher in
constraints. This notion is supported by the high prevalence of cardiac patients with VaD, there was no major difference between the two
disorders (89% of EGb 761®-treated patients and 83% of the patients subgroups with respect to severity of neuropsychiatric symptoms.
receiving placebo) and the number of AEs related to hypertension and This ties in with the findings of a large population-based study which
cardiovascular disorders, predominantly in the placebo group. also found similar frequencies and severities of neuropsychiatric
symptoms for AD and VaD [40]. In our study patients with VaD
seemed to have somewhat more difficulty in performing tasks of
Table 4
Adverse events (AEs) observed in at least 5% of patients of any aetiological subgroup or everyday life, which probably reflects more physical incapacity due to
treatment group and all serious adverse events (SAF; numbers (percent) of patients) preceding strokes. Higher scores for dizziness and tinnitus in the VaD
patients may point to vascular component of such disturbances of the
AD VaD
neurosensory system.
EGb 761® Placebo EGb 761® Placebo
(n = 106) (n = 112) (n = 94) (n = 88)
The total incidence of AEs tended to be slightly higher in the VaD
Adverse events
subgroup. In particular, angina pectoris, dizziness, headache and
Headache 23(21.7%) 37(33.0%) 26(27.7%) 48(54.5%) cough occurred more frequently in VaD patients. However, in both
Angina pectoris 6(5.7%) 13(11.6%) 14(14.9%) 22(25.0%) types of dementia patients treated with EGb 761® were less likely to
Dizziness 5(4.7%) 16(14.3%) 7(7.4%) 20(22.7%) suffer an AE than those who received placebo. Specifically, events that
Back pain 5(4.7%) 7(6.3%) 7(7.4%) 15(17.0%)
may be due to vascular pathology are observed less frequently under
Diarrhoea 7(6.6%) 12(10.7%) 11(11.7%) 4(4.5%)
Tinnitus 8(7.5%) 9(8.0%) 1(1.1%) 9(10.2%) EGb 761® treatment. This underscores the excellent tolerability and
Cough 2(1.9%) 3(2.7%) 12(12.8%) 8(9.1%) safety of the product.
Influenza 6(5.7%) 7(6.3%) 8(8.5%) 4(4.5%) In conclusion, the subgroup analyses demonstrated that the
Hypertensive crisis 8(7.5%) 9(8.0%) 2(2.1%) 3(3.4%) Ginkgo biloba extract EGb 761® was safe and effective in the treatment
Upper respiratory tract infection 8(7.5%) 9(8.0%) 7(7.4%) 3(3.4%)
of both major types of dementia, AD and VaD. This may be an
Blood pressure increased 1(0.9%) 8(7.1%) 3(3.2%) 5(5.7%)
Abdominal pain 5(4.7%) 2(1.8%) 6(6.4%) 6(6.8%) advantage in the management of patients with mixed pathologies,
Nausea 3(2.8%) 6(5.4%) 2(2.1%) 2(2.3%) when none of the two diagnoses can readily be established, in
Arthralgia – 1(0.9%) 5(5.3%) 4(4.5%) particular in a primary care setting.
Dysgeusia – 1(0.9%) 5(5.3%) –

Serious adverse events

Angina pectoris 2(1.9%) 4(3.6%) 4(4.3%) 6(6.8%) Acknowledgement
Hemiparesis – – 1(1.1%) 1(1.1%)a
Hypoaesthesia – – – 1(1.1%)a The clinical trial was sponsored by Dr. Willmar Schwabe GmbH &
a
Same patient. Co. KG, Karlsruhe, Germany.

Please cite this article as: Napryeyenko O, et al, Efficacy and tolerability of Ginkgo biloba extract EGb 761® by type of dementia: Analyses of a
randomised controlled trial, J Neurol Sci (2009), doi:10.1016/j.jns.2009.02.353
 ARTICLE IN PRESS
6 O. Napryeyenko et al. / Journal of the Neurological Sciences xxx (2009) xxx–xxx
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