[Disorders of brain performance of vascular origin. Randomized double-blind study of the effectiveness of Gingko biloba extract]. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. Efficacy of Ginkgo biloba in 90 outpatients with cerebral insufficiency caused by old age Results of a placebo-controlled double-blind trial. A randomized, double-blind, placebo-controlled trial of two doses of Ginkgo biloba extract in dementia of the Alzheimer's type. Interaction between psychological and pharmacological treatment in cognitive impairment. A double-blind, placebo controlled study of Ginkgo biloba extract ('tanakan') in elderly outpatients with mild to moderate memory impairment. [Primary degenerative dementia: therapy with Ginkgo biloba extract. Placebo-controlled double-blind and comparative study]. Ginkgo biloba and donepezil: a comparison in the treatment of Alzheimer's dementia in a randomized placebo-controlled double-blind study. [The effect of Ginkgo biloba extract on neurophysiological and psychometric measurement results in patients with psychotic organic brain syndrome. A double-blind study against placebo]. [Treatment of cerebral aging disorders with Ginkgo biloba extract. A longitudinal multicenter double-blind drug vs. placebo 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. [Cerebral insufficiency--treatment with Ginkgo-biloba extract. Time of onset of effect in a double-blind study with 60 inpatients]. Clinical efficacy of Ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type. [Effect of Ginkgo-biloba extract on mental performance. Double-blind study using computerized measurement conditions in patients with cerebral insufficiency]. [Effectiveness of brief infusions with Ginkgo biloba Special Extract EGb 761 in dementia of the vascular and Alzheimer type]. Treatment of age-related memory complaints with Ginkgo biloba extract: a randomized double blind placebo-controlled study.
nan 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. The efficacy of the Ginkgo biloba special extract LI 1370 was tested in a double-blind trial comprising 90 outpatients with cerebral insufficiency. The average age of the patients was 62.7 years. The trial was conducted over a period of 12 weeks. Significant improvements in the patient's performance were observed under verum compared to the placebo preparation which was administered to a control group of patients among which the relevant disorder were distributed homogeneously. The effects of the preparation were recorded in respect of specific performance parameters and are summarized as follows: - Stabilization of time intervals in respect of the quality of information processing processes. It was shown by the study that the test preparation should be used over a minimum period of time, since improvements of some of the parameters were not observed until the 6th week of treatment. The clinical efficacy of LI 1370 was clearly established.
                Copyright © 1994 Gustav Fischer Verlag, Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved. 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. In contrast to other kinds of psychotropic drugs, nootropics or cognition enhancing drugs may be indicated, not for the direct treatment of the pathology itself, but for improving or restoring the remaining brain functions. Brain functions are normally trained during various kinds of non-medical therapy, such as physiotherapy, speech therapy, occupational therapy, memory training etc... In research little attention has been paid to the combination of both kinds of therapeutic approaches, probably because of the important methodological difficulties. This combination however, offers various interesting perspectives: L. ISRAEL examined in two placebo-controlled studies the effects of either 160 mg/d of ginkgo biloba extractum (GBE) or piracetam 2.4 or 4.8 g/d, combined with a memory training program, in nondemented patients complaining of memory problems. The results of both studies suggest that nootropic drug treatment and memory training have each an effect on different cognitive functions and, hence, are complementary. Some functions, like attention/perception in the GBE study and learning in the piracetam study, seem to benefit from both treatments, suggesting a mutually potentiating effect of drug treatment and training. This potentiation is very clear in the treatment of dyslexic children: in a placebo-controlled study piracetam 3.3 g/d, in combination with normal school teaching and more specific logopedic therapy, allowed a normal progression during the full school year in reading accuracy and reading comprehension, while the placebo treated children getting a similar training progressed only with 50%. Recently promising results were obtained in the treatment of dysphasic patients with a combination of speech therapy and piracetam 4.8 g/d, especially when given during the first months after the stroke, or otherwise in combination with an intensive speech training. In both double-blind studies the piracetam treated group improved about 60% more than the group who only got speech therapy and placebo. All these data may be explained by the restorative or enhancing influence of nootropic drugs on neurotransmitter systems closely related to learning and memory functions. E.g. piracetam restores the availability and function of muscarinic and NMDA receptors in aging animals, most probably through a modulation of the psychico-chemical properties of the neuronal membrane such as the membrane fluidity. 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. nan 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 range of typical symptoms of cerebro-organic syndrome such as dizziness, memory and concentration loss, and orientation disorders can either be measured objectively within a clinical trial or can be observed subjectively. Thirty-six patients with classical symptoms of organic syndrome were recruited into a placebo-controlled double-blind trial in which the therapeutic effect of Ginkgo biloba extract EGb 761 (rökan) was measured by the following objective criteria: quantified EEG, saccadic eye movements and psychometric tests (Wiener Determination Test, Number Connection Test). Following 2 weeks' wash-out, 40 mg. EGb 761 was administered 3 times daily (= 120 mg daily dose) for 8 weeks. The control group received placebo capsules of identical external appearance. The tests listed above were carried out prior to treatment and after 4 and 8 weeks' therapy with the exception of quantitative EEG which was recorded at the beginning and end of treatment only. Patients presenting with pathological findings for at least two of the four test criteria were admitted to the trial. Patients receiving unpermitted supplementary medication or suffering from acute cardiovascular disturbances or digestive and metabolic disorders were excluded from the trial. A highly significant difference could already been seen after 4 weeks of therapy and also after 8 weeks in the results of both the saccadic test and the psychometric tests compared to the placebo control group. Saccade duration was shortened and the latency reduced. In parallel, the number of correct answers given in the Wiener Determination Test and Number Connection Test increased significantly compared to the control group. (ABSTRACT TRUNCATED AT 250 WORDS) The effectiveness of Ginkgo biloba extract in the treatment of cerebral disorders due to ageing was evaluated in a multicentric, double-blind, drug versus placebo trial involving 166 patients. In this study carried out under strict methodological conditions a specially devised geriatric clinical evaluation scale was used. The results confirmed that Ginkgo biloba extract is effective against cerebral disorders due to ageing. The difference between control and treatment groups became significant at 3 months and increased during the following months. These results were concordant with the overall clinical assessment made by the specialist in charge. 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. Sixty inpatients with cerebral insufficiency and the leading symptom depressive mood, were treated in a double-blind study for 6 weeks with a daily dose of 160 mg Ginkgo biloba extract or placebo. After 2, 4 and 6 weeks, changes in 12 typical symptoms in comparison with the last examination, were evaluated. In the group receiving placebo, small, but progressive improvements were observed. In the Ginkgo-biloba group, the overall number of improvements was significantly larger. After 2 weeks the differences were marked for only a few of the symptoms; after 4 and 6 weeks in contrast, in 11 of the 12 symptoms. The largest number of improvements in the Ginkgo-biloba group was observed between the 2nd and 4th weeks of treatment. In this period, about two-thirds of the patients on Ginkgo-biloba, and about one-fifth of the patients on placebo showed improvements. 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. Problem: The effect of ginkgo biloba extract EGb 761 on basic parameters of mental performance. Patients: Seventy-two outpatients with cerebral insufficiency at three test centers. Study design: Double-blind, randomized placebo-controlled study of 24 weeks duration. Test parameters: Psychometric computer-aided examination of the short-term memory and basic learning rate. Results: Statistically significant improvement in the shortterm memory after 6 weeks and of the learning rate after 24 weeks in the test substance group, but not in the placebo group (longitudinal analysis). The difference between the test substance and placebo groups (horizontal analysis) reached statistical significance in the 24th week. Conclusions: Treatment with ginkgo biloba extract EGb 761 improves mental/mnestic performance. In a placebo-controlled, randomized, double-blind clinical trial, 40 patients with a mean age of 68 (+/- 12.5) years suffering from moderate dementia (Alzheimer, vascular, or mixed type) according to DSM-III-R criteria were included. Severity of the disease had to correspond to stages 4 or 5 of Reisberg's Global Deterioration Scale. Infusions of either EGb 761 or placebo were administered 4 days per week for 4 weeks. Primary outcome measure was the activities of daily living as assessed by the Nürnberger-Alters-Beobachtungsskala (NAB). The Clinical Global Impressions of change (CGI, item 2) and the actual intelligence as assessed by the Kurztest für Allgemeine Intelligenz (KAI) were further target variables. No relevant group differences could be detected at baseline. After therapy, patients of the active substance group scored significantly better (p < 0.05) on each outcome measure than those who received placebo. Using a sequential testing procedure, a global significance level of p < 0.05 could be assured. Superiority of EGb 761 therapy was also found with respect to a self-rating scale for instrumental activities of daily living (Nürnberger-Alters-Alltagsaktivitätenskala), the improvement of the most prominent symptom of illness, and the decrease of depression. Thus clinical efficacy of EGb 761 could be shown on three planes of assessment: the behavioral, the psychopathologic and the psychometric plane. It could be confirmed that, in patients with moderate dementia, short-term intravenous infusion therapy with EGb 761 results in an improvement of psychopathology and cognitive performance, which is reflected in an increased ability to cope with the demands of daily living. A growing number of people is subject to age-related cognitive impairment due to the proportional increase of the ageing population. Therefore, there is a growing interest in cognition-enhancing substances. The efficacy of an alcohol/water extract of Ginkgo biloba in elderly individuals with memory- and/or concentration complaints was tested in a randomized, double-blind, placebo-controlled study by using both subjective and objective parameters. After a wash-out period of 4 weeks 241 non-institutionalised patients in the age range 55-86 years were randomly allocated to receive either Ginkgo biloba alcohol/water extract in a high dose (HD), a low dose (LD) or a placebo (PL) for 24 weeks. Patients were assessed using a psychometric testbattery in the following order: Expended Mental Control Test (EMCT) measuring attention and concentration, Benton Test of Visual Retention-Revised (measures short term visual memory), Rey Test part 1 (measures short term memory and learning curve), Beck Depressive Inventory (BDI) measuring the presence and severeness of a depression in order to exclude depressive patients and Rey Test part 2 (measures long term memory: recognition). Furthermore, subjective perception of memory and concentration was measured. 197 patients completed the study (mean MMSE score: 26.29). In the subjective test, the EMCT, the Rey 1 and Rey 2 no significant differences in improvement in time between the groups were observed. In the Benton test increases of 18%, 26% and 11% (expressed as percentage of baseline scores) were observed in the HD, LD and PL respectively (MANOVA; p = 0.0076). No substantial correlation was observed between subjective perception of the severeness of memory complaints and the objective test results. No differences in the number of (gastrointestinal) side effects were observed between placebo and verum groups. These results indicate that the use of Ginkgo extracts in elderly individuals with cognitive impairment might be promising. Further research using both subjective and objective measurements is recommended.
                Copyright © 1998 Gustav Fischer Verlag. Published by Elsevier GmbH.. All rights reserved.