Alzheimer's Disease / Cognition / Memory + Ginkgo biloba
Anti-neuroinflammatory effects of Ginkgo biloba extract EGb761 in LPS-activated primary microglial cells
Brahim Gargouri a Johanna Carstensen a Harsharan S.Bhatia a Michael Huellb Gunnar P.H.Dietzc Bernd L. Fiebich.
Abstract
Background
Neuroinflammation is a key factor of Alzheimer's disease (AD) and other neurodegenerative conditions. Microglia are the resident mononuclearimmune cells of the central nervous system (CNS). They play an essential role in the maintenance of homeostasis and responses to neuroinflammation. Ginkgo biloba extract EGb 761 is one of the most commonly used natural medicines owing to its established efficacy and remarkable biological activities especially in respect to CNS diseases. However, only few studies have addressed the effects and mechanisms of Ginkgo biloba extract in microglia activation.
Methods
We measured the production of pro-inflammatory mediators and cytokines by ELISA and analyzed gene expressions by qRT-PCR and Western Blot in LPS treated cultured primary rat microglia.
Results
The Ginkgo biloba extract EGb 761 significantly inhibited the release of prostaglandin E2 (PGE2) and differentially regulated the levels of pro-inflammatory cytokines. The inhibition of LPS-induced PGE2 release in primary microglia was partially dependent on reduced protein synthesis of mPGES-1 and the reduction in the activation of cytosolic phospholipase A2(cPLA2) without altering COX-2 enzymatic activity, inhibitor of kappa B alpha (IkappaBalpha) degradation, and the activation of multiple mitogen activated protein kinases (MAPKs). Altogether, we showed that EGb 761 reduces neuro-inflammatory activation in primary microglial cells by targeting PGE2release and cytokines.
Conclusion
Ginkgo biloba extract EGb 761 displayed anti-neuroinflammatory activity in LPS-activated primary microglia cells. EGb 761 was able to reduce neuroinflammatory activation by targeting the COX/PGE2 pathway. This effect might contribute to the established clinical cognitive efficacy in Alzheimer's disease, vascular and mixed dementia.
Source : Journal Phytomedicine
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Protection Efficacy of the Extract of Ginkgo biloba against the Learning and Memory Damage of Rats under Repeated High Sustained +Gz Exposure
Liang-En Chen, Feng Wu, Andong Zhao, Hua Ge, and Hao Zhan
Abstract
Repeated high sustained positive Gz (+Gz) exposures are known for the harmful pathophysiological impact on the brain of rats, which is reflected as the interruption of normal performance of learning and memory. Interestingly, extract of Ginkgo biloba (EGb) has been reported to have neuroprotective effects and cognition-enhancing effects. In this study, we are interested in evaluating the protective effects of EGb toward the learning and memory abilities. Morris Water Maze Test (MWM) was used to evaluate the cognitive function, and the physiological status of the key components in central cholinergic system was also investigated. Our animal behavioral tests indicated that EGb can release the learning and memory impairment caused by repeated high sustained +Gz. Administration of EGb to rats can diminish some of the harmful physiological effects caused by repeated +Gz exposures. Moreover, EGb administration can increase the biological activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) but reduce the production of malondialdehyde (MDA). Taken together, our study showed that EGb can ameliorate the impairment of learning and memory abilities of rats induced by repeated high sustained +Gz exposure; the underlying mechanisms appeared to be related to the signal regulation on the cholinergic system and antioxidant enzymes system.
Source : Evidence Based Complementary and Alternative Medicine
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Systematic Review of EGb 761® in Dementia with Behavioral and Psychological Symptoms
von Gunten A, Schlaefke S, Überla K.
Efficacy of Ginkgo biloba extract EGb 761® in dementia with behavioural and psychological symptoms: A systematic review. World J Biol Psychiatry. August 27, 2015; [epub ahead of print]. doi: 10.3109/15622975.2015.1066513.
Behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms, occur in 80-100% of patients with this condition. However, many studies evaluating dementia treatments exclude patients with BPSD. Meta-analyses evaluating the efficacy of EGb 761® (Dr. Willmar Schwabe GmbH & Co. KG; Karlsruhe, Germany), a proprietary ginkgo (Ginkgo biloba, Ginkgoaceae) leaf extract, for the treatment of dementia have produced equivocal conclusions. There are several new studies that assessed patients with BPSD that were not included in the meta-analyses. Hence, this systematic review was conducted to evaluate the safety and efficacy of EGb 761 for the treatment of dementia in patients who have clinically significant BPSD.
The following electronic databases were searched: PubMed (from inception through December 2013), EMBASE (January 2006 through December 2013), and PASCAL (inception through December 2013). Also, the reference sections of systematic reviews were screened and the manufacturer of EGb 761 was queried for unpublished research. The inclusion criteria were as follows: (1) randomized, placebo-controlled, double-blind, clinical trials assessing the effects of oral EGb 761 in patients with Alzheimer's disease (AD), vascular dementia (VaD), or mixed dementia, with a study duration of ≥ 22 weeks; (2) the patients enrolled were diagnosed with dementia according to the Diagnostic and Statistical Manual of Mental Disorders III-R and IV (DSM-III-R, DSM-IV),International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10), National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA), or the National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS/AIREN); (3) had clinically significant BPSD as defined by minimal scores on the Neuropsychiatric Inventory (NPI) or other appropriate rating scales; (4) outcome measures were defined for BPSD and at least two of the three typical domains of assessment, namely, cognition, activities of daily living (ADL), and clinical global assessment (CGA); and (5) methodological quality was adequate (randomization, allocation concealment, and blinding; sample size estimation; numbers and disposition of patients who discontinued the trial prematurely; and statistical analyses were reported and judged adequate).
A total of four trials met the inclusion criteria. The manufacturer of EGb 761 provided the individual patient data from the studies so that the data could be pooled for analysis. The studies took place in Bulgaria (n = 1); Ukraine (n = 2); and Republic of Belarus, Republic of Moldova, and Russian Federation (multinational study, n = 1). In total, there were 1628 patients who were randomly assigned, and 1598 were included in the full analysis set (n = 796, EGb 761 and n = 802, placebo). Dropout rates were low (2-8%) and similar between groups. The mean age for the total population was 66 years. All studies evaluated 240 mg/day EGb 761 for 22-24 weeks. Baseline scores were similar between groups and across studies.
An analysis of covariance model was used to evaluate the effects of EGb 761 compared to placebo for the cognition, BPSD, ADL, and quality-of-life (QoL) domains; an analysis of variance model was used to assess CGA. In the case of the ADL and CGA domains where different outcome measures were used in different trials, the results were standardized within each individual trial to create a dimensionless measure. Treatment effects for the cognition, BPSD, ADL, and QoL domains were presented as standardized least mean squares differences (LMSD), and CGA was expressed as least mean squares. Standardized mean differences (Cohen's D) was used to compare overall effect sizes; standardized effect sizes of 0.2, 0.5, and 0.8 were classified as small, moderate, and large effects, respectively. Statistical significance was assumed with P < 0.05.
The short cognitive performance test (SKT) was used to evaluate cognition in all four trials. Three of the four studies demonstrated that EGb 761 was significantly superior to placebo; the numerical improvement in the fourth study did not reach statistical significance. In the pooled analysis, EGb 761 was significantly better than placebo (P < 0.001). The overall effect size was moderate.
All four of the studies demonstrated that EGb 761 was significantly better than placebo on the NPI total score assessing BPSD and the NPI caregiver distress score measuring BPSD-related caregiver distress. The pooled analysis indicated that EGb 761 was significantly better than placebo (P < 0.001). The overall effect size was moderate.
ADL assessments showed that in all four studies and in the pooled analysis, EGb 761 was significantly better than placebo (P < 0.001). The overall effect size was moderate.
CGAs showed that in three studies EGb 761 was significantly better than placebo; however, in one study there was no significant difference between groups. The pooled analysis revealed that EGb 761 was significantly better than placebo (P < 0.001). The overall effect size was moderate to large.
Only two of the four studies evaluated QoL. In both studies, and in the pooled analysis, EGb 761 was statistically superior to placebo (P < 0.001). The overall effect size was small.
Subgroup analysis of the three diagnostic subpopulations (AD, VaD, and mixed) revealed that EGb 761 was significantly better than placebo for all outcomes, except QoL for patients with VaD. The authors speculate that the lack of effect on QoL in the VaD group may be due to a lack of statistical power in this very small subsample or there may be different determinants of QoL for patients with VaD.
To evaluate whether the benefits were clinically meaningful, response rates and numbers needed to treat (NNTs) were calculated. NNTs of 6-9 are considered clinically meaningful in placebo-controlled trials of psychotropic drugs. In the present analysis, EGb 761 had NNTs of 4-5 for each outcome measure, indicating that it produced a clinically meaningful benefit.
The frequency of adverse events was similar between groups. "There was no clustering of any type of event in the EGb 761 treated patients."
Overall, the effect sizes were moderate for the domains of cognition, BPSD, ADL, and CGA, while the effect on QoL was small. The authors concluded that EGb 761 was statistically and clinically superior to placebo in improving cognitive performance, BPSD, functional abilities, and overall condition. Accordingly, caregiver distress decreased. Limitations are that none of the trials evaluated postponement of nursing home placement, and it is uncertain whether these results can be extrapolated to patients with severe BPSD. Although studies suggest that treatment benefits increase with increasing severity of BPSD, there are no published trials evaluating the efficacy of EGb 761 for the treatment of patients with severe BPSD.
This systematic review is unique and valuable because the authors conducted large-scale pooled analyses of individual patient data. This is opposed to the typical meta-analysis where authors evaluate mean data extracted from a published report. The pooled analyses support the conclusion that 240 mg/day EGb 761 is safe and moderately effective for the treatment of outpatients with dementia and mild to moderate BPSD.
Two of the authors (A. von Gunten and K. Überla) received consultant honoraria from Dr. Willmar Schwabe GmbH & Co. KG, and the third (S. Schlaefke) is a salaried employee of the company.
—Heather S. Oliff, PhD
Source : American Botanical Council, Herbclip
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Meta-Analysis Demonstrates Safety and Efficacy of Defined Ginkgo Extract for Treating Dementia in Elderly
by Amy C. Keller
Reviewed: Gauthier S, Schlaefke S. Efficacy and tolerability of Ginkgo biloba extract EGb 761® in dementia: a systematic review and meta-analysis of randomized placebo-controlled trials. Clin Interv Aging. 2014;9:2065-2077.
Many older adults suffer from Alzheimer’s disease (AD) or other cerebrovascular diseases. The leading clinically tested proprietary ginkgo (Ginkgo biloba, Ginkgoaceae) leaf extract EGb 761® has shown a variety of mechanisms related to treating AD in vivo, including repairing mitochondrial function, modulating neuroplasticity, and increasing dopamine concentrations in only frontal brain areas.
EGb 761 is an acetonic (60% per weight) dry extract of ginkgo leaves standardized to contain 22-27% ginkgo flavonglycosides, 5-7% terpene lactones (2.8-3.4% ginkgolides A, B, and C, and 2.6-3.2% bilobalide), and less than 5 parts per million ginkgolic acids. It is produced by Dr. Willmar Schwabe GmbH & Co. KG of Karlsruhe, Germany.
Processing methods and bioactive compound content are integral to establishing the efficacy and safety of botanicals and may greatly differ among products. This systematic review and meta-analysis investigates clinical trials using the standardized product EGb 761 for the treatment of AD and/or vascular dementia (VaD). The statistical analysis performed in this study was funded by Schwabe; one of the authors (Schlaefke) is an employee of the company.
This study searched the databases PubMed (to December 2012), EMBASE (2006-2011), and PASCAL (to December 2011). Included clinical trials were randomized, placebo-controlled, and double-blind, with a duration of 20 weeks or more. The included trials used EGb 761 for the treatment of AD, VaD, or a combination of the two conditions, according to diagnostic requirements from a variety of internationally recognized sources of criteria. Also, trials must have used two of the three following outcome measures: cognition, activities of daily living (ADL), and clinical global impression. Trials with patients having other mental deficiencies or that incorporated EGb 761 in conjunction with cholinesterase inhibitors (e.g., donepezil [Aricept®] and tacrine [Cognex®]) were excluded.
The study authors located 15 randomized, placebo-controlled, clinical trials of EGb 761; of these, eight were excluded due to failure to meet the inclusion criteria listed above. Patients from the seven included trials were prescribed a dosage of 120 mg (two trials) or 240 mg (six trials) of EGb 761 for 22-26 weeks (one trial tested both dosages). The Jadad Scale, used to evaluate the trial quality (scores range from 1 to 5, with 5 indicating the highest trial robustness), indicated “appropriate”quality, with scores of 3 for two trials and 5 for five trials. From the trials, 2,625 patients were evaluated, with 1,396 taking EGb 761 and 1,229 taking placebo. Females comprised 50% to 86% of the patient population in the studies, and patients ranged from 63 to 79 years old. Physical metrics such as height, weight, body mass index, and cognitive metrics were not different at baseline between treatment and placebo groups.
The seven included trials used two different but overlapping validated cognitive assessment tools. Five of the trials reported significant beneficial effects on cognition for those taking EGb 761 as compared to those in the placebo group (P=0.03). These effects were found to be dose dependent, and those taking 240 mg of EGb 761 had significantly better cognitive performance than those in the placebo group (P=0.04). ADL was measured by four different scales. Those taking EGb 761 scored significantly better as compared to those in the placebo group (P<0.001), and those taking 240 mg had a significantly greater improvement in ADL than those in the placebo group (P=0.001).
In clinical global impression assessments using three different rating scales, those taking EGb 761 rated significantly better than those taking placebo (P=0.01); this was also observed in those taking 240 mg of EGb 761 as compared to those in the placebo group (P=0.007). In general, the odds ratio for cognitive improvement in those taking EGb 761 as compared to placebo was 2.48 (95% confidence intervals [CI]: 1.17, 5.28; P=0.02). The odds ratio for improvement in clinical global impression for EGb 761 treatment as compared to placebo was 3.18 (95% CI: 1.78, 5.67; P<0.0001).
In two of the studies, slightly more patients taking EGb 761 experienced adverse side effects (ASEs) than those taking the placebo; however, in the other five trials, those with ASEs were equally distributed between groups. The relative risk ratio for ASEs with EGb 761 was 0.96 (95% CI: 0.90, 1.01). Likewise, “serious” ASEs were comparable in all trials across the treatment groups. In both treatment and placebo groups, ASEs included headache, dizziness, hypertension, tinnitus, angina pectoris, and respiratory tract infection. The ASEs causing early termination of patient participation in either group were symptoms typical of dementia, including agitation, anxiety, insomnia, or unspecific symptoms such as constipation, nausea, headache, and dizziness.
Overall, the results of this meta-analysis suggest that 240 mg daily intake of EGb 761 is effective in improving cognition, ADL, and clinical global impression in those suffering from AD and/or VaD, with minimal adverse side effects. This phytomedicinal formulation may be a useful adjuvant therapy in those suffering from cognitive decline.
Source : Herbal Gram - American Botanical council
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The Ginkgo biloba Extract EGb 761 Modulates Proteasome Activity and Polyglutamine Protein Aggregation
Marcel Stark and Christian Behl
Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, 55099 Mainz, Germany
Abstract
The standardized Ginkgo biloba extract EGb 761 has well-described antioxidative activities and effects on different cytoprotective signaling pathways. Consequently, a potential use of EGb 761 in neurodegenerative diseases has been proposed. A common characteristic feature of a variety of such disorders is the pathologic formation of protein aggregates, suggesting a crucial role for protein homeostasis. In this study, we show that EGb 761 increased the catalytic activity of the proteasome and enhanced protein degradation in cultured cells. We further investigated this effect in a cellular model of Huntington’s disease (HD) by employing cells expressing pathologic variants of a polyglutamine protein (polyQ protein). We show that EGb 761 affected these cells by (i) increasing proteasome activity and (ii) inducing a more efficient degradation of aggregation-prone proteins. These results demonstrate a novel activity of EGb 761 on protein aggregates by enhancing proteasomal protein degradation, suggesting a therapeutic use in neurodegenerative disorders with a disturbed protein homeostasis.
....It was shown that in Alzheimer's Disease the treatment with EGb 761 provides protective effects through a combination of antioxidative [5], free radical scavenging [6], antiamyloidogenic [7], and antiapoptotic properties [8].
Source : Evidence Based Complementary and Alternative Medicine
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Evidence of Ginkgo Extract Efficacy in Patients with Dementia and as an Adjunct for Treating Patients with Chronic Schizophrenia
By Healther S. Oliff PhD
Reviewed: Brondino N, De Silvestri A, Re S, et al. A systematic review and meta-analysis of Ginkgo biloba in neuropsychiatric disorders: from ancient tradition to modern-day medicine. Evid Based Complement Alternat Med. 2013;2013:1-11. doi: 10.1155/2013/915691.
Ginkgo (Ginkgo biloba, Ginkgoaceae) extract is one of the most popular phytomedicines; however, according to the authors, there has been no systematic review on its effect on neuropsychiatric disorders other than dementia. Hence, the purpose of this report was to conduct a systematic review of ginkgo clinical trials for such disorders.
The authors searched MEDLINE®, Embase™, PsycINFO®, and the Cochrane Database of Systematic Reviews from inception through April 2012. The search terms were gingko biloba, ginkgo, ginko, gingko, bilobalid* [asterisk commands search to locate all terms that start with the preceding word], egb 761, dementia, cognitive impairment, Alzheimer, autism, autistic spectrum disorder, schizophrenia, psychosis, psychotic disorder, delusion, depression, major depression, depressive symptom, anxiety, generalized anxiety disorder, anxious, attention deficit disorder, ADHD, attention deficit, hyperactivity, and addiction. According to the article, “All search terms were searched individually in each database and combined together. The search strategy had no time restriction but was limited to articles in English, Italian, French, Spanish, and German. Additionally, all recovered papers were reviewed for further relevant references.” Study inclusion criteria were randomized, controlled clinical trials; a minimum of 10 patients per group; and treatment for less than six weeks. When possible, the data were pooled for a meta-analysis.
A total of 1,109 studies were identified. Of these, 113 were obtained for additional evaluation, and 18 met the inclusion criteria and were incorporated in this review. There was one randomized, double-blind study of patients with attention deficit hyperactivity disorder, which included 50 children treated with 80 mg/day (for participants weighing < 30 kg) or 120 mg/day ginkgo compared with methylphenidate for six weeks. Methylphenidate — a psychostimulant marketed under several trade names, including Ritalin® — was much more effective than ginkgo, though the latter had significantly fewer adverse side effects.
There was one randomized, placebo-controlled study of patients with autism, which included 47 children who were treated with the antipsychotic drug risperidone (on the market as Risperdal® and generic) in addition to either 80 mg/day (if < 30 kg) or 120 mg/day ginkgo extract or placebo for 10 weeks. There was no significant difference between groups, which means that no added effect for risperidone could be shown for ginkgo extract.
There was one randomized, double-blind, placebo-controlled study in patients with cocaine addiction, which included 44 patients who received either 240 mg/day ginkgo extract, the nootropic piracetam, or placebo for 10 weeks. There was no significant difference among the three groups.
There was one randomized, placebo-controlled study in patients with generalized anxiety disorder (GAD) or adjustment disorder with anxious mood in which participants were treated with 240 mg/day ginkgo, 480 mg/day ginkgo, or placebo for four weeks. There was a significant dose-response improvement in the ginkgo-treated patients compared with placebo-treated patients.
There was one randomized, placebo-controlled study of medicated patients with chronic schizophrenia and tardive dyskinesia who were treated with 240 mg/day ginkgo extract or placebo for 12 weeks. The ginkgo group had a significant improvement in the Abnormal Involuntary Movement Scale but not on secondary outcomes — namely the psychopathological scales — as the placebo group also showed improvements over time.
There were three other randomized, controlled studies in patients with chronic schizophrenia treated with ginkgo extract and either clozapine, haloperidol, or olanzapine (antipsychotic drugs), and these data were pooled for meta-analysis. The studies with clozapine and haloperidol were double-blind and placebo-controlled (n=42 and n=109, respectively), and the third study was olanzapine-controlled (n=29). The pooled analysis favored ginkgo; however, the results had substantial heterogeneity (i.e., when looking at the individual outcome measures, not all outcomes favored ginkgo treatment).
There were 10 studies of dementia; eight placebo-controlled and two donepezil-controlled. (Donepezil [sold as Aricept® and DONEP] is an acetylcholinesterase inhibitor.) Only the eight placebo-controlled studies (which utilized 120 or 240 mg/day ginkgo for 12-52 weeks) could be included in a meta-analysis. All trials used the standardized extract EGb 761® (Dr. Willmar Schwabe GmbH & Co. KG; Karlsruhe, Germany). The methodological quality of the eight studies was judged to be “adequate.” The pooled data showed that the Alzheimer’s Disease Assessment Scale-cognitive subscale and Syndrom-Kurz test outcome measures favored ginkgo treatment. There was also a significant difference in activities of daily living (ADL) standardized change scores between treatment groups when combining different scales: the Alzheimer’s Disease Activities-of-Daily-Living International Scale, Geriatric Evaluation by Relatives Rating Instrument, Gottfries-Bråne-Steen-Activities of Daily Living scale, Nürnberger Alters-Alltagsaktivitäten-Skala, and Nürnberger Alters-Beobachtungsskala. The two studies comparing donepezil and ginkgo showed no significant differences between treatments.
The authors conclude that the general lack of evidence prevents them from drawing conclusions for most neuropsychiatric conditions. However, the meta-analysis of dementia studies shows that ginkgo provides benefits for cognition and ADL. The authors state that the benefits for dementia and schizophrenia were modest and that some studies showed statistical improvements that were not necessarily clinically meaningful. Nonetheless, the authors conclude that despite heterogeneous results, the evidence supports the use of the proprietary standardized ginkgo extract in patients with dementia and as an adjunct therapy for patients with schizophrenia.
Source : HerbalGram. 2013; American Botanical Council
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Efficacy and Tolerability of Ginkgo Extract in Treatment of Alzheimer’s Disease and Vascular Dementia
by Heather S. Oliff
Reviewed: Ihl R, Tribanek M, Bachinskaya N; for the GOTADAY Study Group. Efficacy and tolerability of a once daily formulation of Ginkgo biloba extract EGb 761® in Alzheimer’s disease and vascular dementia: Results from a randomised controlled trial. Pharmacopsychiatry. 2012;45(2):41-46. Many studies have demonstrated the safety and efficacy of 240 mg (120 mg 2x/day) of ginkgo (Ginkgo biloba, Ginkgoaceae) special extract EGb 761® (Dr. Willmar Schwabe GmbH and Co. KG Pharmaceuticals; Karlsruhe, Germany). Patient compliance is better when patients are required to take fewer daily doses. Therefore, the manufacturer developed a once-daily 240 mg dose of EGb 761. The once-daily dose was tested and found to be safe and efficacious in a previous trial.1 The goal of the present study was to learn more about efficacy in different types of dementia. This was accomplished by conducting a subgroup analysis of the total population of a randomized, controlled, double-blind, multicenter study.
Since the methods have been described previously, they were mentioned only briefly in this report. Patients were recruited from the outpatient clinic of the Department of Psychiatry of the National Medical University in Kiev, Ukraine, and 19 outpatient clinics of neurological or psychiatric hospitals in Ukraine between April and November 2006. The study included outpatients (n=410, aged ≥ [equal to or greater than] 50 years) with mild to moderate dementia due to probable Alzheimer’s disease (AD), possible AD with cerebrovascular disease (CVD), or vascular dementia (VaD).
Clinical diagnosis of AD was established via the criteria of the National Institute of Neurological and Communicative Disorders and Stroke together with the Alzheimer’s Disease and Related Disorders Association (NINCDS/ADRDA); VaD was established according to the diagnostic criteria published by the National Institute of Neurological Disorders and Stroke together with the Association Internationale pour la Recherche et l’Enseignement en Neurosciences (NINDS/AIREN); and possible AD with CVD was established according to the relevant subsets of those criteria. A recent (≤ [equal to or less than] 1 year old) CT or MRI scan had to be consistent with the clinical diagnosis.
Other inclusion criteria included a score of ≤ 35 on the Test for the Early Detection of Dementia with Differentiation from Depression (TE4D), a total score of 9-23 on the SKT (Erzigkeit’s short syndrome test) cognitive test battery, a total score of ≥ 5 on the 12-item Neuropsychiatric Inventory (NPI), and at least one item score (other than delusion or hallucination) of ≥ 3 on the NPI. Patients were excluded if they had significant psychiatric disorders (e.g., major depression or subsyndromal depression), severe somatic disorders, or were taking a medication that could have influenced the assessment scores. Patients were treated with 240 mg EGb 761 or placebo 1x/day for 24 weeks. The primary outcome measures were the SKT and NPI.
A total of 404 patients were included in the analysis, with 333 patients diagnosed as having AD (probable AD: n=121 and possible AD with CVD: n=212) and 71 patients diagnosed as having VaD. Treatment adherence was 99%. For the SKT total score, both subgroups taking EGb 761 had an improvement from baseline by 1.4 points, which was significantly better than the placebo-treated group (AD, P<0.001 and VaD, P<0.05). For the NPI score, VaD patients treated with EGb 761 responded better to treatment than the patients with AD treated with EGb 761 (4.5 point improvement vs 2.9 points, respectively) (P-value not reported). Also for the NPI score, EGb 761-treated patients with AD and VaD improved significantly more than placebo-treated patients (AD, P=0.001 and VaD, P<0.05). When looking at clinically meaningful improvements (decrease in SKT scores by ≥ 3 points or decrease in NPI by ≥ 4 points), 33% of EGb 761-treated patients with AD compared with 14% of placebo-treated patients with AD had clinical improvement on the SKT (P<0.001), and 43% of EGb 761-treated patients with AD compared with 22% of placebo-treated patients with AD had clinical improvement on the NPI (P<0.001). The number of patients with VaD showing clinical improvement was similar to that in patients with AD, but, due to the small size of the VaD subsample, the ginkgo-placebo difference was not statistically significant (for SKT, EGb 761-treated: 28% vs. placebo-treated: 19%, and for NPI, EGb 761-treated: 54% vs. placebo-treated: 31%).
For all secondary outcome variables (NPI caregiver distress score, the Clinical Global Impression of Change as adapted by the Alzheimer’s Disease Cooperative Study [ADCS-CGIC], the Alzheimer’s Disease Activities of Daily Living International Scale [ADL-IS], and the Verbal Fluency Test), except the dementia quality-of-life scale, there were statistically significant differences between the EGb 761 group and the placebo group in AD as well as in VaD. Quality of life was significantly improved only in AD.
The AD subgroup was further broken down into probable AD and possible AD with CVD. The authors state, “There were no conspicuous differences in efficacy related to vascular pathology.”
According to the authors, the most frequently reported adverse events (AEs) were reported with similar frequency among treatment groups, and there were no major bleeding events (data were not provided).
The authors believe that the study population represents everyday practice. The authors conclude that EGb 761 had “essentially similar” effects in patients with AD and VaD. They also think that the data support the use of EGb 761 for dementia as diagnosed in the primary care setting since EGb 761 had similar efficacy for both populations. The study was sponsored by the manufacturer of EGb 761.
—Heather S. Oliff, PhD
Reference
1. Ihl R, Bachinskaya N, Korczyn A, et al. Efficacy and safety of a once-daily formulation of Ginkgo biloba extract EGb 761® in dementia with neuropsychiatric features: A randomized controlled trial. Int J Geriatr Psychiatry. 2011; 26(11):1186-1194.
Source : HerbalGram. 2012; American Botanical Council
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