No abstract

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.

EGb 761, 240 mg once-daily, was found significantly superior to placebo in the treatment of patients with dementia with neuropsychiatric symptoms.

No abstract

Objective: The study was conducted to explore the effects of EGb 761® (Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany) on neuropsychiatric symptoms (NPS) and cognition in patients with mild cognitive impairment (MCI). Methods: One hundred and sixty patients with MCI who scored at least 6 on the 12-item Neuropsychiatric Inventory (NPI) were enrolled in this double-blind, multi-center trial and randomized to receive 240 mg EGb 761 daily or placebo for a period of 24 weeks. Effects on NPS were assessed using the NPI, the state sub-score of the State-Trait Anxiety Inventory and the Geriatric Depression Scale. Further outcome measures were the Trail-Making Test (A/B) for cognition and global ratings of change. Statistical analyses followed the intention-to-treat principle. Results: The NPI composite score decreased by 7.0 ± 4.5 (mean, standard deviation) points in the EGb 761-treated group and by 5.5 ± 5.2 in the placebo group (p = 0.001). Improvement by at least 4 points was found in 78.8% of patients treated with EGb 761 and in 55.7% of those receiving placebo (p = 0.002). Superiority of EGb 761 over placebo (p < 0.05) was also found for the State-Trait Anxiety Inventory score, the informants' global impression of change, and both Trail-Making Test scores. There were statistical trends favoring EGb 761 in the Geriatric Depression Scale and the patients' global impression of change. Adverse events (all non-serious) were reported by 37 patients taking EGb 761 and 36 patients receiving placebo. Conclusions: EGb 761 improved NPS and cognitive performance in patients with MCI. The drug was safe and well tolerated.

Estimates of substrate oxidation obtained from appearance of 13C or 14C from tracers in breath must be corrected for retention of labeled carbon in the body. We aimed to determine the effect of a defined experimental diet and metabolic status on recovery of infused Na [13C]bicarbonate in breath. Six healthy male subjects consumed an experimental diet for 7 days before receiving a continuous infusion of formula without tracer on day 8 and received either an intragastric (ig) or intravenous (iv) infusion of Na [13C]bicarbonate on day 9 or 11 during a 4-h postabsorptive (PA), 4-h continuously fed period. A trend toward increasing PA breath enrichment during the first 7 diet days approached statistical significance (P = 0.051), whereas breath enrichments measured 3 h postbreakfast were consistently higher than PA values throughout and did not change over the 7-day period. Breath enrichments during a 4-h continuous ig infusion of formula without tracer on day 8 rose 2.0 +/- 0.5 atom percent excess (APE).10(-3) above base line (P less than 0.001, ANOVA). In the tracer studies, breath enrichments were similar for the ig and iv routes of tracer infusion. For the ig infusion the fraction of infused Na [13C]bicarbonate recovered in breath as 13CO2 was 0.74 +/- 0.02 for the PA period and 0.79 +/- 0.02 for the fed period. For the iv infusion the fraction recovered was 0.70 +/- 0.04 for the PA period and 0.82 +/- 0.03 for the fed period. Fractional recoveries were not significantly different for ig and iv routes of administration but were different for PA and fed periods (P less than 0.0001, 2-way ANOVA). The fractional recoveries for the fed period obtained here were similar to the value 0.81 reported in a number of other studies. Recovery of tracer in breath increased linearly with O2 uptake and CO2 production, suggesting that factors affecting respiratory gas exchange may alter recovery. We conclude that the primary factor determining label recovery is the immediate and recent nutritional status of the host.

Objective: To explore the treatment effect of EGb 761^® (EGb) in Alzheimer’s disease depending on baseline severity. Methods: We applied stratification to the intent-to-treat data set collected during a 52-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study with 120 mg of EGb, using cutoff points of 23 and 14 for the Mini-Mental State Examination (MMSE) score. Outcome measures used were the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog) and the Geriatric Evaluation by Relative’s Rating Instrument (GERRI). Results: In the severity stratum 1 (MMSE >23), the placebo group did not show significant changes, while the EGb group improved significantly by 1.7 points on the ADAS-Cog and by 0.09 points on the GERRI. In the severity stratum 2 (MMSE <24), the placebo group worsened by 4.1 points on the ADAS-Cog and 0.18 points on the GERRI, whereas the EGb group showed 60% less decline on the ADAS-Cog (treatment difference of 2.5 points) and no change on the GERRI (treatment difference of 0.25 points). The most severely impaired subgroup (MMSE <15) showed slightly more pronounced worsening for both treatment groups. However, in comparison to placebo, EGb induced virtually the same magnitude of effect as was observed in the entire stratum 2. Conclusions: The results of this retrospective analysis indicated that a treatment effect favorable to EGb could be observed with respect to cognitive performance (p = 0.02) and social functioning (p = 0.001) regardless of the stage of dementia, whether mild or moderately severe. However, the relative changes from baseline measured at endpoint depended heavily on the severity at baseline. Improvement was observed in the group of patients with very mild to mild cognitive impairment, while in more severe dementia, the mean EGb effect should be considered more in terms of stabilization or slowing down of worsening, as compared to the greater deterioration observed with placebo.

BackgroundVascular cognitive impairment (VCI) is a complex spectrum encompassing post-stroke cognitive impairment (PSCI) and small vessel disease-related cognitive impairment. Despite the growing health, social, and economic burden of VCI, to date, no specific treatment is available, prompting the introduction of the concept of a disease modifier.Consensus and suggestionsWithin this clinical spectrum, VCI and PSCI remain advancing conditions as neurodegenerative diseases with progression of both vascular and degenerative lesions accounting for cognitive decline. Disease-modifying strategies should integrate both pharmacological and non-pharmacological multimodal approaches, with pleiotropic effects targeting (1) endothelial and brain–blood barrier dysfunction; (2) neuronal death and axonal loss; (3) cerebral plasticity and compensatory mechanisms; and (4) degenerative-related protein misfolding. Moreover, pharmacological and non-pharmacological treatment in PSCI or VCI requires valid study designs clearly stating the definition of basic methodological issues, such as the instruments that should be used to measure eventual changes, the biomarker-based stratification of participants to be investigated, and statistical tests, as well as the inclusion and exclusion criteria that should be applied.ConclusionA consensus emerged to propose the development of a disease-modifying strategy in VCI and PSCI based on pleiotropic pharmacological and non-pharmacological approaches.