Here are abstracts on some of the ingredients contained in TF Recall.
4Life
Transfer Factor ReCall
Ingredient Abstracts
Huperzine A, a potential therapeutic agent for treatment of Alzheimer's disease.
Bai DL, Tang XC, He XC. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai, 200031, China.
Curr Med Chem 2000 Mar;7(3):355-74
HupA is a potent, reversible and selective inhibitor of AChE with a rapid absorption and penetration into the brain in animal tests. It exhibits memory-enhancing activities in animal and clinical trials. Compared to tacrine and donepezil, HupA possesses a longer duration of action and higher therapeutic index, and the peripheral cholinergic side effects are minimal at therapeutic doses. This review article deals with a comprehensive survey of the progress in chemical and pharmacological studies of HupA including the isolation and structure elucidation, pharmacological actions, total synthesis, SAR studies and the future development of HupA. Recently, it has been reported that HupA could reduce neuronal cell death caused by glutamate. The dual bio-activities of HupA would further enhance its value and potentiality as the therapeutic agent for Alzheimer s disease.
Huperzine A, a novel promising acetylcholinesterase inhibitor.
Cheng DH; Ren H; Tang XC State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, P.R. China.
Neuroreport (ENGLAND) Dec 20 1996, 8 (1) p97-101
The effects of huperzine A on memory impairments induced byscopolamine were valuated using a radial maze task and inhibition of cholinesterase in vitro compared with the effects of E2020 and tacrine. Scopolamine (0.2 mg kg-1) significantly impaired spatial memory in rats. Huperzine A (0.1-0.4 mg kg-1, p.o.), E2020 (0.5-1.0 mg kg-1, p.o.) and tacrine (1.0-2.0 mg kg-1, p.o.) could reverse these scopolamine-induced memory deficits. The ratios of huperzine A, E2020 and tacrine for butyrylcholinesterase:acetylcholinesterase determined by a colourimetric method were 884.57, 489.05, and 0.80, respectively. The results demonstrated that huperzine A was the most selective acetylcholinterase inhibitor, and improved the working memory deficit induced by scopolamine significantly better than did E2020 or tacrine, suggesting it may be a promising agent for clinical therapy of cognitive impairment in patients with Alzheimer's Disease.
Huperzine A improves cognitive deficits caused by chronic cerebral hypoperfusion in rats.
Wang LM, Han YF, Tang XC. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 200031, Shanghai, People's Republic of China.
Eur J Pharmacol 2000 Jun 9;398(1):65-72
The effects of (-)-huperzine A, a promising therapeutic agent for Alzheimer's disease, on learning behavior and on alterations of the cholinergic system, the oxygen free radicals and energy metabolites induced by permanent bilateral ligation of the common carotid arteries were investigated in rats. Daily oral administration of huperzine A produced a significant improvement of the deficit in the learning of the water maze task, beginning 28 days after ischemia, correlating to about 33-40% inhibition of acetylcholinesterase activity in cortex and hippocampus. Huperzine A significantly restored the decrease in choline acetyltransferase activity in hippocampus and significantly reduced the increases in superoxide dismutase, lipid peroxide, lactate and glucose to their normal levels. The present findings demonstrate that the improvement by huperzine A of the cognitive dysfunction in the late phase in chronically hypoperfused rats is due to its effects, not only on the cholinergic system, but also on the oxygen free radical system and energy metabolism. Our results strongly suggest that huperzine A has therapeutic potential for the treatment of dementia caused by cholinergic dysfunction and/or decrease of cerebral blood flow.
Effects of phosphatidylserine in Alzheimer's disease
Crook T, Petrie W, Wells C, Massari DC Memory Assessment Clinics, Inc., Bethesda, MD 20814. USA
Psychopharmacol. Bull. (USA), 1992, 28/1 (61-66)
We studied 51 patients meeting clinical criteria for probable Alzheimer's disease (AD). Patients were treated for 12 weeks with a formulation of bovine cortex phosphatidylserine (BC-PS; 100 mg t.i.d.) or placebo, and those treated with the drug improved on several cognitive measures relative to those administered placebo. Differences between treatment groups were most apparent among patients with less severe cognitive impairment. Results suggest that phosphatidylserine may be a promising candidate for study in the early stages of AD.
Double-blind randomized controlled study of phosphatidylserine in senile demented patients.
Delwaide PJ, Gyselynck-Mambourg AM, Hurlet A, Ylieff M.
Acta Neurol Scand 1986 Feb;73(2):136-40
A double-blind randomized controlled study was conducted in 42 hospitalized demented patients to evaluate the therapeutical effect of phosphatidylserine (BS-PS). Half of the patients received 3 X 100 mg of this product, and the other half a placebo of the same appearance. After a wash-out period, prescription lasted for six weeks. To evaluate the patients, two distinct rating scales were used: the Crichton Scale and an original one (Peri Scale) designed in our geriatric unit (see Appendix). A circle crossing test was added. Out of the 35 patients who completed the trial, 18 had received placebo and 17 BC-PS. The results indicated a trend toward improvement in the BC-PS treated patients and an analysis of covariance showed a significant (p less than 0.05) treatment effect on the Peri Scale. The results at the end of the treatment period were compared with those obtained three weeks later. Here again there was a statistically significant difference in the Peri Scale results, indicating that modifications are drug-related. The behavioral improvement shown in this study is in agreement with experimental studies on aged animals.
Double-blind cross-over study of phosphatidylserine vs. placebo in patients with early dementia of the Alzheimer type . Engel RR, Satzger W, Gunther W, Kathmann N, Bove D, Gerke S, Munch U, Hippius H. Psychiatric Hospital, University of Munich, Germany.
Eur Neuropsychopharmacol 1992 Jun;2(2):149-55
Thirty-three patients with mild primary degenerative dementia according to DSM-III (MMS between 15 and 27) took part in a double-blind cross-over study of phosphatidylserine (Fidia, 300 mg/d) versus placebo. Both treatment phases lasted for 8 weeks with an 8 week washout phase in between and a 4 week washout phase before treatment phase one. Clinical global improvement ratings showed significantly more patients improving under BC-PS than under placebo during treatment phase one. The improvement carried over to the following wash-out and treatment phases. There were no significant improvements in GBS dementia rating scale, psychometric tests or P300-latency. 16-channel EEG mapping findings indicated that the patients initially showed higher power values in all frequency bands (except alpha), when compared to a younger, healthy control group. BC-PS reduced the higher power values compared to placebo, shifting EEG power more towards the normal level.
N-Acetylcysteine enhances T cell functions and T cell growth in culture
INT. IMMUNOL. (United Kingdom), 1993, 5/1 (97-101
N-Acetylcysteine (NAC) is highly nontoxic for peripheral blood T cells and immunostimulatory enhancing T cell functions such as mitogenesis, interleukin-2 (IL-2) production, and growth in culture. NAC has been proposed for the treatment of AIDS based on its inhibition of human immunodeficiency virus (HIV) replication in cultured cells. Therefore its effect on normal T cells from 10 young donors and one elderly donor has been investigated as a prelude to clinical consideration. T cell function was evaluated in the presence and absence of accessory cells. With concanavalin A and anti-CD3 activation, NAC enhanced mitogenesis by similar2- to 2.5-fold at 5-10 mM. Mitogenesis of purified T cells with anti-CD2 was not affected by NAC; in the presence of accessory cells, NAC enhanced mitogenesis by similar2-fold at 1-10 mM. Importantly, NAC levels above 10 mM completely inhibited activation of peripheral blood mononuclear cells by anti-CD2. IL-2 secreted by T cells was also enhanced by NAC, similar1.5-fold, but IL-2 secreted by cells from old donors was enhanced by 3-fold. In cultures of peripheral blood T cells, NAC (10 mM) stimulated growth by at least 4- to 6-fold after two passages. These results show that NAC, nontoxic even at 20 mM, is an effective enhancer of T cell function and a remarkable enhancer of growth. Results from other laboratories show that NAC, which increases glutathione levels, suppresses HIV replication presumably via suppression of the activation of transcriptional factor NF-kappa B. For normal T cells, however, this mechanism does not appear applicable because IL-2 production, regulated by several factors including NF-kappa B, is enhanced by NAC. Rather, glutathione may enhance the activity of other transcriptional factors modulating IL-2 expression. NAC did exhibit one inhibitory characteristic, however, towards T cell adhesion. Slow cluster formation, induced by PMA, was moderately inhibited (0-30%) by 5-10 mM NAC in cells from most donors studied.
N-acetylcysteine (NAC) enhances interleukin-2 but suppresses interleukin-4 secretion from normal and HIV+ CD4+ T-cells.
Cell Mol Biol (Noisy-le-grand) (FRANCE) 1995, 41 Suppl 1 pS35-40
We find that purified CD4+ T cells from 30 HIV+ individuals have a suppressed Interleukin-4 (IL-4) production compared to normal controls regardless of activator (anti-CD3 or Con A) or co-activator [phorbol ester (PMA or anti-CD28)], generally by 2-4 fold. In every case, the cells producing IL-4 respond more strongly to anti-CD28 co-activation than to PMA, ie, 1150 pg/ml compared to 2070 pg/ml for controls and 398 pg/ml compared to 1250 pg/ml for HIV+ cells, respectively. In contrast, anti-CD3 with PMA gives a more vigorous IL-2 response than with anti-CD28, ie, 37.3 ng/ml compared to 12.3 ng/ml for controls and 28.5 ng/ml versus 15.1 ng/ml for HIV+ cells, respectively. These data are not compatible with the TH1/TH2 switch hypothesis since IL-4 production is decreased, not increased for CD4+ HIV+ T-cells and while IL-2 production is decreased with PMA, it is not decreased significantly with anti-CD28. Interestingly, 5 mM N-acetylcysteine (NAC) acts as an immunoenhancer; mitogenesis was enhanced 2 fold or more in general for control and HIV+ CD4+ T-cells and IL-2 production was enhanced 2-3 fold for anti-CD3 (with PMA or anti-CD28) for both controls and HIV+ CD4+ cells. However, NAC suppressed IL-4 production induced by anti-CD3 and anti-CD28 in both control and HIV+ CD4+ T cells. In the other cases, it produced in general no significant change.
N-acetylcysteine enhances antibody-dependent cellular cytotoxicity in neutrophils and mononuclear cells from healthy adults and human immunodeficiency virus-infected patients.
J Infect Dis (UNITED STATES) Dec 1995, 172 (6) p1492-502
Patients with AIDS have decreased levels of the intracellular antioxidant, glutathione, in their circulating lymphocytes and plasma. N-acetylcysteine (NAC) increases intracellular stores of glutathione and has direct antioxidant properties. In this study, the effects of glutathione and NAC on the cytotoxicity of neutrophils and mononuclear cells were tested using cells from healthy controls and human immunodeficiency virus (HIV)-infected patients. NAC (1 and 5 mM) enhanced the antibody-dependent cellular cytotoxicity (ADCC) of neutrophils from healthy adult controls and HIV-infected adults and children. The antineoplastic drug, 1,3 bis(2-chloroethyl)-1-nitrosourea (BCNU), which depletes intracellular glutathione, inhibited the ADCC of neutrophils; the addition of NAC partially reversed this inhibition. Similar effects of BCNU and NAC were seen when the cytotoxicity of mononuclear cells was tested using CEM tumor cells bearing the HIV gp120 antigen as targets. Thus, NAC enhances various forms of cytotoxicity and may be beneficial to AIDS patients whose defects in leukocyte cytotoxicity may be due to glutathione depletion.
Glutathione precursor and antioxidant activities of N-acetylcysteine and oxothiazolidine carboxylate compared in in vitro studies of HIV replication.
AIDS Res Hum Retroviruses (UNITED STATES) Aug 1994, 10 ( p961-7
N-Acetyl-L-cysteine (NAC) and L-2-oxothiazolidine 4-carboxylate (OTC) are pro-GSH drugs that been proposed for AIDS therapy. In this article we compare the antiviral activities of these compounds in various in vitro HIV infection models. Although both compounds blocked cytokine induction of HIV in acute and chronic infection models, and in HIV-LTR reporter cell systems, NAC was far more effective than OTC, even at suboptimal doses. To test whether this difference is due to GSH conversion efficacies of these compounds, we measured GSH restoration by NAC or OTC in GSH-depleted peripheral blood mononuclear cells (PBMCs), using flow cytometry. In isolated PBMCs, NAC fully replenishes depleted intracellular GSH whereas OTC only minimally replenishes GSH. This ability to replenish GSH in vitro and its ability to scavenge free radicals directly explain why NAC has more potent antiviral activities in vitro.
Effects of the sulphydryl donor N-acetyl-L-cysteine on nerve conduction, perfusion, maturation and regeneration following freeze damage in diabetic rats.
Eur J Clin Invest (ENGLAND) Aug 1996, 26 ( p698-706
Peripheral nerve conduction velocity deficits in diabetic rats depend on decreased nerve perfusion, which may be related to increased free radical activity and impaired endogenous protection by the glutathione redox cycle. We studied the effect of treatment with the glutathione precursor N-acetyl-L-cysteine on nerve conduction, blood flow, maturation and regeneration. Two months of diabetes in mature rats caused 20% and 48% deficits in sciatic motor conduction velocity and endoneurial blood flow, respectively, which were largely corrected by N-acetyl-L-cysteine treatment during the second month. In young nondiabetic rats, sciatic motor conduction velocity increased by 31% over 6 weeks. Diabetes halved the conduction velocity maturation rate, however N-acetyl-L-cysteine treatment allowed a normal pattern of development. After 1 month of treated or untreated diabetes, the sciatic nerve was lesioned by a liquid nitrogen-cooled probe. Myelinated fibre regeneration distance, determined electrophysiologically, was reduced by 12.2% with diabetes; this was prevented by N-acetyl-L-cysteine treatment. Thus, the data stress the importance of free radical-mediated changes in the aetiology of experimental diabetic neuropathy.
A comparison of the protective effects of N-acetyl-cysteine and S-carboxymethylcysteine against paracetamol (acetaminophen)-induced hepatotoxicity.
Toxicology (NETHERLANDS) Nov 1983
The protective effect of the sulphur-containing amino acids N-acetyl-cysteine and S-carboxymethylcysteine against paracetamol-induced hepatotoxicity was evaluated in the hamster by biochemical and histological methods. Of the animals receiving paracetamol alone 25% died within 24 h following administration. All surviving animals showed acute hepatocellular injury and marked loss of cytochrome P-450 and hepatic mixed-function oxidase activities. Simultaneous administration of N-acetylcysteine decreased the mortality rate, partly prevented the paracetamol-induced liver damage and partly restored enzyme activities. Simultaneous administration of S-carboxymethylcysteine with paracetamol afforded no protection. Kidneys from all animals were histologically normal. Human liver microsomes and liver microsomes from 3-methylcholanthrene-pretreated hamsters metabolished paracetamol to intermediate(s) that bind covalently to microsomal proteins. The rate of covalent binding was inhibited markedly by N-acetylcysteine and to a lesser extent by S-carboxylmethylcysteine.
Nacystelyn, a novel lysine salt of N-acetylcysteine, to augment cellular antioxidant defence in vitro.
Respir Med (ENGLAND) Mar 1997, 91 (3) p159-68
Nacystelyn (NAL), a recently-developed lysine salt of N-acetylcysteine (NAC), and NAG, both known to have excellent mucolytic capabilities, were tested for their ability to enhance cellular antioxidant defence mechanisms. To accomplish this, both drugs were tested in vitro for their capacity: (1) to inhibit O2- and H2O2 in cell-free assay systems; (2) to reduce O2- and H2O2 released by polymorphonuclear leukocytes (PMN); and (3) for their cellular glutathione (GSH) precursor effect. In comparison with GSH, NAL and NAC inhibited H2O2, but not O2-, in cell-free, in vitro test systems in a similar manner. The anti-H2O2 effect of these drugs was as potent as that of GSH, an important antioxidant in mammalian cells. To enhance cellular GSH levels, increasing concentrations (0-2 x 10(-4) mol l-1) of both substances were added to a transformed alveolar cell line (A549 cells). After NAC administration (2 x 10(-4) mol l-1), total intracellular GSH (GSH + 2GSSG) levels reached 4.5 +/- 1.1 x 10(-6) mol per 10(6) cells, whereas NAL increased GSH to 8.3 +/- 1.6 x 10(-6) mol per 10(6) cells. NAC and NAL administration also induced extracellular GSH secretion; about two-fold (NAC), and 1.5-fold (NAL), respectively. The GSH precursor potency of cystine was about two-fold higher than that of NAL and NAC, indicating that the deacetylation process of NAL and NAC slows the ability of both drugs to induce cellular glut production and secretion. Buthionine-sulphoximine, which is an inhibitor of GSH synthetase, blocked the cellular GSH precursor effect of all substances. In addition, these data demonstrate that NAC and NAL reduce H2O2 released by freshly-isolated cultured blood PMN from smokers with chronic obstructive pulmonary disease (COPD) (n = 10) in a similar manner (about 45% reduction of H2O2 activity by NAC or NAL at 4 x 10(-6) mol l-1). In accordance with the results obtained from cell-free, in vitro assays, O2- released by PMN was not affected. Ambroxol (concentrations: 10(-9)-10(-3) mol l-1) did not reduce activity levels of H2O2 and O2- in vitro. Due to the basic effect of dissolved lysine, which separates easily in solution from NAL, the acidic function of the remaining NAC molecule is almost completely neutralized [at concentration 2 x 10(-4) M: pH 3.6 (NAC), pH 6.4 (NAL)]. Due to their function as H2O2 scavengers, and due to their ability to enhance cellular glutathione levels, NAL and NAC both have potent antioxidant capabilities in vitro. The advantage of NAL over NAC is two-fold; it enhances intracellular GSH levels twice as effectively, and it forms neutral pH solutions whereas NAC is acidic. Concluding from these in vitro results, NAL could be an interesting alternative to enhance the antioxidant capacity at the epithelial surface of the lung by aerosol administration.
Attention deficit and infantile hyperactivity.
Berdonces JL. Universitat de Barcelona.
Rev Enferm 2001 Jan;24(1):11-4
Hyperactivity is a very common disorder in children (specially males) that today is considered as a clinical syndrome by scientific medicine. American Psychiatric Association establishes 10 symptoms to diagnose it, but they can be resumed in three characteristics: Impulsivity, Distraction, and Hyperactivity. There are different ways to treat it, but psychiatric medication has major risks in children. From complementary medicine we can find several aids in changing diet patterns and supplementing with vitamins or minerals. Chocolate, sugar, sweeteners, additives, preservatives, dyes, can enhance the incidence of this syndrome; instead the supplementation with lipids rich in PUFA's can prevent it. B complex vitamins, magnesium, copper, manganese or calcium can be interesting and in herbal medicine, sedative plants like passion flower, valerian or lemon balm are useful aids. Also liquorice, fennel and berries can be used for different physiological actions.
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Ginkgo biloba extract: mechanisms and clinical indications.
Diamond BJ, Shiflett SC, Feiwel N, Matheis RJ, Noskin O, Richards JA, Schoenberger NE Department of Research, Center for Research in Complementary and Alternative Medicine, Kessler Medical Rehabilitation Research and Education Corporation, West Orange, NJ 07052, USA.
Arch Phys Med Rehabil 2000 May;81(5):668-78
OBJECTIVE: Ginkgo biloba may have a role in treating impairments in memory, cognitive speed, activities of daily living (ADL), edema, inflammation, and free-radical toxicity associated with traumatic brain injury (TBI), Alzheimer's dementia, stroke, vasoocclusive disorders, and aging. The purpose of this review is to provide a synthesis of the mechanisms of action, clinical indications, and safety of Ginkgo biloba extract.
DATA SOURCES: Empirical studies, reviews, chapters, and conference proceedings were identified in the following databases: Medline, the Research Council for Complementary Medicine based on the British Library database, and Psychlnfo. Ginkgo biloba, EGb 761, Tanakan, Tebonin, Rokan, and LI 1370 were the principal index terms.
STUDY SELECTION AND DATA EXTRACTION: Controlled clinical studies with both positive and negative findings are included, in addition to animals studies illustrating mechanisms of activity.
DATA SYNTHESIS: Ginkgo has shown activity centrally and peripherally, affecting electrochemical, physiologic, neurologic, and vascular systems in animals and humans with few adverse side effects or drug interactions. Ginkgo shows promise in patients with dementia, normal aging, and cerebrovascular-related disorders. Clinical indications include memory, information processing, and ADL.
CONCLUSIONS: Ginkgo shows promise in treating some of the neurologic sequelae associated with Alzheimer's disease, TBI, stroke, normal aging, edema, tinnitus, and macular degeneration. Mechanisms of action may include antioxidant, neurotransmitter/receptor modulatory, and antiplatelet activating factor properties. While safe, caution is advised when recommending ginkgo to patients taking anticoagulants. Future studies should examine dose effects, component activity, mechanisms, and clinical applications
The Ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by beta-amyloid.
Bastianetto S, Ramassamy C, Dore S, Christen Y, Poirier J, Quirion R Douglas Hospital Research Centre, Department of Psychiatry, McGill University, 6875 Bld LaSalle, Verdun, Quebec, Canada.
Eur J Neurosci 2000 Jun;12(6):1882-90
Substantial evidence suggests that the accumulation of beta-amyloid (Abeta)-derived peptides, and to a lesser extent free radicals, may contribute to the aetiology and/or progression of Alzheimer's disease (AD). Ginkgo biloba extract (EGb 761) is a well-defined plant extract containing two major groups of constituents, i.e. flavonoids and terpenoids. It is viewed as a polyvalent agent with a possible therapeutic use in the treatment of neurodegenerative diseases of multifactorial origin, e.g. AD. We have investigated here the potential effectiveness of EGb 761 against toxicity induced by (Abeta)-derived peptides (Abeta25-35, Abeta1-40 and Abeta1-42) on hippocampal primary cultured cells, this area being severely affected in AD. A co-treatment with EGb 761 concentration-dependently (10-100 microg/mL) protected hippocampal neurons against toxicity induced by Abeta fragments, with a maximal and complete protection at the highest concentration tested. Similar, albeit less potent protective effects were seen with the flavonoid fraction of the extract (CP 205), while the terpenes were ineffective. Most interestingly, EGb 761 (100 microg/mL) was even able to protect (up to 8 h) hippocampal cells from a pre-exposure to Abeta25-35 and Abeta1-40. EGb 761 was also able to both protect and rescue hippocampal cells from toxicity induced by H2O2 (50-150 microM), a major peroxide possibly involved in mediating Abeta toxicity. Moreover, EGb 761 (10-100 microg/mL), and to a lesser extent CP 205 (10-50 microg/mL), completely blocked Abeta-induced events, e.g. reactive oxygen species accumulation and apoptosis. These results suggest that the neuroprotective effects of EGb 761 are partly associated with its antioxidant properties and highlight its possible effectiveness in neurodegenerative diseases, e.g. AD via the inhibition of Abeta-induced toxicity and cell death.
A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group.
Le Bars PL, Katz MM, Berman N, Itil TM, Freedman AM, Schatzberg AF. New York Institute for Medical Research, Tarrytown 10591, USA. NYI@HZI.com
JAMA 1997 Oct 22-29;278(16):1327-32
CONTEXT: 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.
OBJECTIVE: To assess the efficacy and safety of EGb in Alzheimer disease and multi-infarct dementia.
DESIGN: A 52-week, randomized double-blind, placebo-controlled, parallel-group, multicenter study.
PATIENTS: Mildly to severely demented outpatients with Alzheimer disease or multi-infarct dementia, without other significant medical conditions.
INTERVENTION: 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.
PRIMARY OUTCOME MEASURES: Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), Geriatric Evaluation by Relative's Rating Instrument (GERRI), and Clinical Global Impression of Change (CGIC).
RESULTS: 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.
CONCLUSIONS: 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.
A 26-week analysis of a double-blind, placebo-controlled trial of the ginkgo biloba extract EGb 761 in dementia.
Le Bars PL, Kieser M, Itil KZ Memory Centers of America Inc., New York, NY, USA. info@mcai.com
Dement Geriatr Cogn Disord 2000 Jul-Aug;11(4):230-7
This intent-to-treat (ITT) analysis was performed to provide a realistic image of the efficacy that could be expected after 26 weeks treatment with a 120-mg dose (40 mg t.i.d.) of EGb 761 (EGb). The data were collected during a 52-week, double-blind, placebo-controlled, fixed dose, parallel-group, multicenter study. Patients were mildly to severely impaired and diagnosed with uncomplicated Alzheimer's disease or multi-infarct dementia according to ICD-10 and DSM-III-R criteria. The primary outcome measures included the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Geriatric Evaluation by Relative's Rating Instrument (GERRI) and Clinical Global Impression of Change. From 309 patients included in the ITT analysis, 244 patients (76% for placebo and 73% for EGb) actually reached the 26th week visit. In comparison to the baseline values, the placebo group showed a statistically significant worsening in all domains of assessment, while the group receiving EGb was considered slightly improved on the cognitive assessment and the daily living and social behavior. Mean treatment differences favored EGb with 1.3 and 0.12 points, respectively, on the ADAS-Cog (p = 0.04) and the GERRI (p = 0.007). In the group receiving EGb, 26% of the patients achieved at least a 4-point improvement on the ADAS-Cog, compared to 17% with placebo (p = 0.04). On the GERRI, 30% of the EGb group improved and 17% worsened, while the placebo group showed an opposite trend with 37% of patients worsening for 25% improved (p = 0.006). Regarding safety, no differences between EGb and placebo were observed.
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