The GuidAge study: Methodological issues. A 5-year double-blind randomized trial of the efficacy of EGb 761(R) for prevention of Alzheimer disease in patients over 70 with a memory complaint
ABSTRACT Preventive approaches in the field of Alzheimer disease (AD) is important but these trials raise many questions. Which protective factor should be studied? What population should be studied? With which principal and secondary criteria? We present here the design of the ongoing GuidAge Study. In the past, several studies suggest that Ginkgo biloba could have a potential benefit effect on cognitive function. The aim of the GuidAge Study is to evaluate the efficacy of 240 mg/d of EGb 761 in the prevention of AD.
GuidAge is a 5-year double-blind randomized trial conducted in France by a private practice/hospital network of general practitioners and hospital practitioners specializing in memory disorders. This study enrolled elderly subjects with spontaneous memory complaint and the primary outcome is the incidence of AD during a 5 years follow-up period. A total of 2854 subjects were enrolled between March 2002 and September 2004. The age of the study population was 76.8 +/- 4.4 with mean MMSE at entry 27.8 +/- 1.7.
The GuidAge study is the largest study carried out in Europe on the prevention of AD. Final results should be available in 2010.
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ABSTRACT: Most current Alzheimer's disease (AD) therapies in advanced phases of development target amyloid β-peptide (Aβ) production, aggregation, or accumulation. Translational models suggest that anti-Aβ therapies may be highly effective if tested as agents to prevent or delay development of the disease or as therapies for asymptomatic patients with very early signs of AD pathology. However, anti-Aβ therapeutics are currently being tested in symptomatic patients where they are likely to be much less effective or ineffective. The lack of alignment between human clinical studies and preclinical studies, together with predictions about optimal trial design based on our understanding of the initiating role of Aβ aggregates in AD, has created a treatment versus prevention dilemma. In this perspective, we discuss why it is imperative to resolve this dilemma and suggest ways for moving forward in the hopes of enhancing the development of truly effective AD therapeutics.Neuron 01/2011; 69(2):203-13. DOI:10.1016/j.neuron.2011.01.002 · 15.98 Impact Factor
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ABSTRACT: Acetylcholinesterase (AChE) is a key target in the treatment of Alzheimer's disease (AD). We studied the potential anti-AChE activities of Acacia nilotica (Leguminosae) and Rhamnus prinoides (Rhamnaceae) plants that have previously been shown to affect central nervous system activities. Sonicated aqueous extracts of A. nilotica and R. prinoides displayed significant AChE inhibition by about 56 and 53%, respectively, after 5 min incubation at 0.1mg/ml final assay concentration. Inhibition kinetics showed both plant preparations to be mixed inhibitors (specifically non-competitive uncompetitive type). Galanthamine was assayed as a positive control and was found to be a very potent mixed type (competitive non-competitive) inhibitor; IC50 of 0.0004 mg/ml compared to 0.079 mg/ml for A. nilotica and 0.201 mg/ml for R. prinoides. We conclude that although the AChE inhibition by A. nilotica and R. prinoides is not as potent as that of galanthamine, in addition to their known antioxidant and anti-inflammatory activities these plants could provide novel poly-pharmacological leads of potential benefit to the treatment of AD and therefore warrant further investigation.
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ABSTRACT: A new Ginkgo biloba extract P8A (TTL), 70% enriched with terpene trilactones, prevents A beta(1-42) induced inhibition of long-term potentiation in the CA1 region of mouse hippocampal slices. This neuroprotective effect is attributed in large part to ginkgolide J that completely replicates the effect of the extract. Ginkgolide J is also capable of inhibiting cell death of rodent hippocampal neurons caused by A beta(1-42). This beneficial and multi-faceted mode of action of the ginkgolide makes it a new and promising lead in designing therapies against Alzheimer's disease.Neurobiology of aging 08/2007; 30(2):257-65. DOI:10.1016/j.neurobiolaging.2007.05.025 · 4.85 Impact Factor