Clinical efficacy of Ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type. A double-blind, placebo-controlled clinical study on the effect of a standardized ginseng extract on psychomotor performance in healthy volunteers. Efficacy and tolerability of Ginkgo biloba extract EGb 761 by type of dementia: analyses of a randomised controlled trial. A randomized, double-blind, placebo-controlled trial of two doses of Ginkgo biloba extract in dementia of the Alzheimer's type. Ginkgo biloba and donepezil: a comparison in the treatment of Alzheimer's dementia in a randomized placebo-controlled double-blind study. Proof of efficacy of the ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia. A double-blind, placebo controlled study of Ginkgo biloba extract ('tanakan') in elderly outpatients with mild to moderate memory impairment. Ginkgo biloba for the improvement of cognitive performance in multiple sclerosis: a randomized, placebo-controlled trial. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group.
Among the psychiatric illnesses associated with old age primary degenerative dementia of the Alzheimer type (DAT) has gained increasing importance in recent years. Even though a curative treatment of the disease is currently impossible, various drugs can be used to slow down its progression. In the present study the influence of oral treatment with 240 mg/day of Ginkgo bilabo special extract EGb 761 (Tebonin forte, manufactured by Dr Willmar Schwabe, Karlsruhe) on the clinical course of DAT was investigated in a double-blind, randomized, placebo-controlled parallel-group design in 20 outpatients. The duration of treatment was 3 months. The primary outcome variable was the sum score in the SKT-test for the determination of attention and memory. Other psychometric tests (trailmaking test, ADAS, CGI) and electrophysiological investigations (EEG topography) were evaluated descriptively. Although the active-treatment group, with a mean sum score of 19.67 points in the, S.K.T., had a poorer baseline level than the placebo group (18.11 points), it experienced an improvement to 16.78 points under treatment with EGb 761 whereas the placebo group deteriorated to 18.89 points. The differences between the baseline and final values formed the basis for a statistical group comparison, which gave a result favourable to EGb 761, at a significance level of p < .013. In addition to this psychometric confirmation of efficacy, certain descriptive trends were found at the psychopathological (Clinical Global Impression) and dynamic functional (EEG findings) levels, which can be interpreted as evidence of effectiveness of Ginkgo biloba special extract EGb 761 in mild to moderate dementia and of local effects in the central nervous system. Inter-group differences in the ADAS cognitive and non-cognitive subscales did not reach statistical significance, probably because of the small sample size. Various tests of psychomotor performance were carried out in a group of 16 healthy male volunteers given a standardized preparation of Korean ginseng (G 115; 100 mg twice a day for 12 weeks) and in a similar group given identical placebo capsules under double-blind conditions. A favourable effect of G 115 relative to baseline performance was observed in attention (cancellation test), processing (mental arithmetic, logical deduction), integrated sensory-motor function (choice reaction time) and auditory reaction time. However, end performance of the G 115 group was superior statistically to the placebo group only in mental arithmetic. No difference between G 115 and placebo was found in tests of pure motor function (tapping test), recognition (digit symbol substitution) and visual reaction time. No adverse effects were reported. It is concluded that G 115 may be superior to placebo in improving certain psychomotor functions in healthy subjects. 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 or above, with dementia with neuropsychiatric features were treated with EGb 761 (240 mg/day) or placebo for 22 weeks. Patients scored between 9 and 23 on the Short Syndrome Test (SKT), a cross-culturally validated cognitive test battery. Their total score on the Neuropsychiatric Inventory (NPI) was at least 5. Efficacy was assessed by the SKT test battery (primary outcome measure), the Verbal Fluency Test, the Clock-Drawing Test, the NPI, the Hamilton Rating Scale for Depression (HAMD), and the Gottfries-Bråne-Steen Scale (GBS). Applying standard research diagnostic criteria 214 patients were diagnosed with Alzheimer's disease (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<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. Previous studies of Ginkgo biloba extract (GbE) in patients with various forms of cognitive impairment or dementia have shown promising results.
                To determine the clinical efficacy of GbE in mild to moderate dementia of the Alzheimer type.
                Randomized, placebo-controlled, double-blind, parallel-group, multicenter trial.
                Outpatient clinics of universities and private research centers specialized in dementia.
                513 outpatients with uncomplicated dementia of the Alzheimer's type scoring 10 to 24 on the Mini-Mental State Examination and less than 4 on the modified Hachinski Ischemic Score, free of other serious illnesses and not requiring continuous treatment with any psychoactive drug.
                26-week treatment with GbE at daily doses of 120 mg or 240 mg or placebo.
                Cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), Alzheimer's Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC).
                There were no significant between-group differences for the whole sample. There was little cognitive and functional decline of the placebo-treated patients, however. For a subgroup of patients with neuropsychiatric symptoms there was a greater decline of placebo-treated patients and significantly better cognitive performance and global assessment scores for the patients on GbE.
                The trial did not show efficacy of GbE, however, the lack of decline of the placebo patients may have compromised the sensitivity of the trial to detect a treatment effect. Thus, the study remains inconclusive with respect to the efficacy of GbE. The Ginkgo biloba special extract EGb 761 seems to produce neuroprotective effects in neurodegenerative diseases of multifactorial origin. There is still debate about the efficacy of Ginkgo biloba special extract EGb 761 compared with second-generation cholinesterase inhibitors in the treatment of mild to moderate Alzheimer's dementia. Our aim is to assess the efficacy of the Ginkgo biloba special extract E.S. in patients with dementia of the Alzheimer type in slowing down the disease's degenerative progression and the patients' cognitive impairment compared with donepezil and placebo. The trial was designed as a 24-week randomized, placebo-controlled, double-blind study. Patients aged 50-80 years, suffering from mild to moderate dementia, were allocated into one of the three treatments: Ginkgo biloba (160 mg daily dose), donepezil (5 mg daily dose), or placebo group. The degree of severity of dementia was assessed by the Syndrom Kurz test and the Mini-Mental State Examination. Clinical Global Impression score was recorded to assess the change in the patients' conditions and the therapeutic efficacy of tested medications. Our results confirm the clinical efficacy of Ginkgo biloba E.S. (Flavogin) in the dementia of the Alzheimer type, comparable with donepezil clinical efficacy. There are few published trials that have directly compared a cholinesterase inhibitor with Ginkgo for dementia. This study directly compares a cholinesterase inhibitor with Ginkgo biloba for dementia of the Alzheimer type and could be a valid contribution in this debate. Our study suggests that there is no evidence of relevant differences in the efficacy of EGb 761 and donepezil in the treatment of mild to moderate Alzheimer's dementia, so the use of both substances can be justified. In addition, this study contributes to establish the efficacy and tolerability of the Ginkgo biloba special extract E.S. in the dementia of the Alzheimer type with special respect to moderately severe stages. The efficacy of the ginkgo biloba special extract EGb 761 in outpatients with presenile and senile primary degenerative dementia of the Alzheimer type (DAT) and multi-infarct dementia (MID) according to DSM-III-R was investigated in a prospective, randomized, double-blind, placebo-controlled, multi-center study. After a 4-week run-in period, 216 patients were included in the randomized 24-week treatment period. These received either a daily oral dose of 240 mg EGb 761 or placebo. In accordance with the recommended multi-dimensional evaluation approach, three primary variables were chosen: the Clinical Global Impressions (CGI Item 2) for psychopathological assessment, the Syndrom-Kurztest (SKT) for the assessment of the patient's attention and memory, and the Nürnberger Alters-Beobachtungsskala (NAB) for behavioral assessment of activities of daily life. Clinical efficacy was assessed by means of a responder analysis, with therapy response being defined as response in at least two of the three primary variables. The data from the 156 patients who completed the study in accordance with the study protocol were taken into account in the confirmatory analysis of valid cases. The frequency of therapy responders in the two treatment groups differed significantly in favor of EGb 761, with p < 0.005 in Fisher's Exact Test. The intent-to-treat analysis of 205 patients led to similar efficacy results. Thus, the clinical efficacy of the ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type and multi-infarct dementia was confirmed. The investigational drug was found to be well tolerated. Thirty-one patients over the age of 50 years and showing a mild to moderate degree of memory impairment entered a 6-month double-blind, placebo controlled, parallel group design study to assess the effects of a standardized Ginkgo biloba extract (containing 24% flavonoid glycosides and 6% terpenes) on cognitive function. Patients were allocated at random to receive oral doses of 40 mg Ginkgo biloba extract or identical placebo 3-times daily. Assessments were made at baseline and after 12 and 24 weeks of treatment using a range of psychometric tests. Efficacy data were available for 27 patients (15 in the placebo group and 12 in the active treatment group). Statistical analysis of the data as compared to baseline suggests that Ginkgo biloba extract had a beneficial effect on cognitive function in this group of patients. Performance on the Digit Copying sub-test of the Kendrick battery was significantly improved at both 12 and 24 weeks, while the median speed of response on a computerized version of a classification task also showed a significant superiority over placebo at 24 weeks. To determine if Ginkgo biloba (GB) improves the cognitive performance of subjects with multiple sclerosis (MS).
                Randomized, double-blind, placebo-controlled trial of GB, 120 mg twice a day or placebo for 12 weeks. The primary outcomes were: the long delay free recall from the California Verbal Learning Test-II; the Paced Auditory Serial Addition Test; the Controlled Oral Word Association Test; the Symbol Digit Modalities Test; Useful Field of View Test; and the color-word interference condition from the Stroop Color and Word Test.
                On completion, the GB group (n=20) was 4.5 seconds (95% confidence interval (CI) (7.6, 0.9), P=0.015) faster than the placebo group (n=18) on the color-word interference condition of the Stroop test. Subjects who were more impaired at baseline experienced more improvement with GB (treatment*baseline interaction, F=8.10, P=0.008). We found no differences on the other neuropsychological tests. Subjects on GB reported fewer cognitive difficulties in the Retrospective Memory Scale of the Perceived Deficits Questionnaire than subjects on placebo (1.5 points, 95% CI (2.6, 0.3), P=0.016). No serious drug related side-effects occurred and GB did not alter platelet function assays.
                Overall, GB did not show a statistically significant improvement in cognitive function. A treatment effect trend, limited to the Stroop test, suggests that GB may have an effect on cognitive domains assessed by this test, such as susceptibility to interference and mental flexibility. EGb 761 is a particular extract of Ginkgo biloba used in Europe to alleviate symptoms associated with numerous cognitive disorders. Its use in dementias is based on positive results from only a few controlled clinical trials, most of which did not include standard assessments of cognition and behavior.
                To assess the efficacy and safety of EGb in Alzheimer disease and multi-infarct dementia.
                A 52-week, randomized double-blind, placebo-controlled, parallel-group, multicenter study.
                Mildly to severely demented outpatients with Alzheimer disease or multi-infarct dementia, without other significant medical conditions.
                Patients assigned randomly to treatment with EGb (120 mg/d) or placebo. Safety, compliance, and drug dispensation were monitored every 3 months with complete outcome evaluation at 12, 26, and 52 weeks.
                Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), Geriatric Evaluation by Relative's Rating Instrument (GERRI), and Clinical Global Impression of Change (CGIC).
                From 309 patients included in an intent-to-treat analysis, 202 provided evaluable data for the 52-week end point analysis. In the intent-to-treat analysis, the EGbgroup had an ADAS-Cog score 1.4 points better than the placebo group (P=.04) and a GERRI score 0.14 points better than the placebo group (P=.004). The same patterns were observed with the evaluable data set in which 27% of patients treated with EGb achieved at least a 4-point improvement on the ADAS-Cog, compared with 14% taking placebo (P=.005); on the GERRI, 37% were considered improved with EGb, compared with 23% taking placebo (P=.003). No difference was seen in the CGIC. Regarding the safety profile of EGb, no significant differences compared with placebo were observed in the number of patients reporting adverse events or in the incidence and severity of these events.
                EGb was safe and appears capable of stabilizing and, in a substantial number of cases, improving the cognitive performance and the social functioning of demented patients for 6 months to 1 year. Although modest, the changes induced by EGb were objectively measured by the ADAS-Cog and were of sufficient magnitude to be recognized by the caregivers in the GERRI.
Currently, there is a lack of convincing evidence to show a cognitive enhancing effect of Panax ginseng in healthy participants and no high quality evidence about its efficacy in patients with dementia. Randomized, double-blind, placebo-controlled, parallel group trials with large sample sizes are needed to further investigate the effect of ginseng on cognition in different populations, including dementia patients.