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- Ginkgo (Ginkgo biloba, Ginkgoaceae)
- EGb 761®
- Cognitive Function
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Date:
08-15-2016 | HC# 071651-550
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Re: EGb 761® Ginkgo Extract Improves Cognitive Flexibility in Elderly Adults
Beck
SM, Ruge H, Schindler C, et al. Effects of Ginkgo
biloba extract EGb 761® on cognitive control functions, mental
activity of the prefrontal cortex and stress reactivity in elderly adults with
subjective memory impairment – a randomized double-blind placebo-controlled
trial. Hum Psychopharmacol.
2016;31(3):227-242.
Studies
indicate that the dopaminergic system in the prefrontal cortex of the brain
modulates attention,
impulse inhibition, prospective memory, and cognitive flexibility. It plays a
key role in cognitive control and stress reactivity, and both of these
functions decline with age. The proprietary ginkgo (Ginkgo biloba, Ginkgoaceae) leaf extract EGb 761® (Dr.
Willmar Schwabe Pharmaceuticals; Karlsruhe, Germany) is a registered drug in
Europe for the treatment of age-related cognitive decline. Evidence from animal
studies and clinical trials indicates that in addition to improving memory, EGb
761 may also enhance dopaminergic function in the prefrontal cortex. Hence, the
objective of this randomized, double-blind, placebo-controlled, parallel-group
study was to evaluate the effect of EGb 761 on prefrontal dopaminergic function
in non-demented elderly people.
Healthy
subjects (n = 62; aged 50-65 years) with subjective memory impairment
participated in this study conducted at the Technische Universität in Dresden,
Germany, from October 2010 to April 2012. Included subjects had (1) subjective memory
impairment as indicated by ≥ 1 question answered with "rather often"
or "very often" or ≥ 5 questions answered "sometimes" on
the Prospective and Retrospective Memory Questionnaire, and (2) had average or
slightly below average cognitive performance on the Wechsler Abbreviated Scale
of Intelligence and the Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological
Battery, revised German edition. Excluded subjects had (1) depression requiring
antidepressive drug treatment within the last 12 months, (2) Beck-Depression-Inventory
revised edition 1996 (BDI-II) score of > 18, (3) other
psychotherapeutic/psychiatric treatment within the 12 months before study commencement,
(4) cerebrovascular disease including stroke, Alzheimer's disease, or other
dementia, or (5) were taking concomitant central nervous system-affecting
medication.
Subjects
received either placebo or 240 mg/day EGb 761 for 56 days. EGb 761 is a 35-67:1
ginkgo leaf extract "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 and contains less than 5-ppm
ginkgolic acids. … Placebo tablets were identical in taste, form, size and
appearance of coating and tablet core."
Stress
reactivity was evaluated with the Trier Social Stress Test (TSST) at baseline
and day 56. Salivary cortisol was measured at baseline and 1, 10, 20, 30, 45,
and 60 min after the TSST. At baseline and day 56, reaction times (RT) and
error rates during the following cognitive tests were assessed: Task-set
Switching, Delayed-Response Task, nonverbal Spatial Stroop Task, daily
prospective memory task, and Go–NoGo Task. All of the cognitive tests were
conducted while the subject was in a functional magnetic resonance imaging (fMRI)
scanner to measure the blood oxygenation level dependent (BOLD) response to the
task; BOLD response is an indirect indicator of neuronal activity. The primary
efficacy endpoints were the TSST, cognitive task performance, and BOLD response.
Safety and tolerability also were evaluated.
Of
the 211 subjects screened, 75 met the study criteria and were randomly assigned
(43 to EGb 761 and 32 to placebo). A total of 13 subjects were excluded from
the per protocol (PP) analysis; 8 subjects (7, EGb 761; 1, placebo) were not
suited for fMRI testing, 3 (2, EGb 761; 1, placebo) were excluded because of
upcoming surgery, and 2 subjects in the EGb 761 group were excluded for
unspecified reasons. One subject taking EGb 761 dropped out because of poor
compliance; therefore, the safety analysis evaluated 32 EGb 761 and 30 placebo
subjects. The efficacy PP analysis included 31 EGb 761 and 30 placebo subjects.
Based on pill counts, compliance amongst the intent-to-treat population was
excellent (99%). The gender ratio was balanced in the EGb 761 group (15 females
and 16 males) but not in the placebo group (18 females and 12 males). There
were no significant differences between groups in other sociodemographic
characteristics; however, mean BDI-II score was significantly higher (P <
0.02) for the EGb 761 group compared to placebo.
EGb
761 significantly improved task-set switching performance (a measure of
cognitive flexibility) compared with placebo (P < 0.02). This effect was
maintained when the analysis was adjusted for baseline differences in BDI-II
score and gender. On
the Go–NoGo Task, the EGb 761 group had a decrease in RT, while the placebo
group had an increase; however, the difference was not statistically
significant even after correcting for BDI-II score and gender. The EGb 761
group also had significantly less false alarms on the Go–NoGo Task (P < 0.05);
however, after controlling for the covariates BDI-II score and gender, the significance
of the effect was decreased (P < 0.052). The EGb 761 group performed better
than the placebo group on the daily prospective memory task; however, the
number of subjects in each group who failed the task was not large enough for
statistical comparison. There were no significant treatment effects on the Delayed-Response
Task, prospective memory task, or BOLD response. The effect of EGb 761 on
salivary cortisol levels was not statistically significant but there was a numerically
superior response, suggesting endocrine stress recovery may have been improved
with EGb 761 treatment.
The
frequency of adverse events (AEs) was higher in the EGb 761 group (n = 19; 54%)
compared with the placebo group (n = 12; 40%). There were no severe or serious
AEs – 2 AEs in each group were moderately severe, and all other AEs were mild;
no subjects terminated treatment due to AEs. The most frequently reported AE
was headache (n = 8; |