R of interventional or observational CPI-203 studies have looked at the potential benefits of various pharmacological treatments. In particular, drugs controlling vascular factors such as statins have received much attention as a result of the growing emphasis on the vascular component of dementia and cognitive decline. However, these studies have yielded contrasting results [1?]. As the neurodegenerative process is accompanied by exacerbated oxidative stress, anti-oxidant vitamins have also been considered as good candidates [7]. Even if the results of the few studies reportingpotential benefits of vitamin E, beta-carotene or multi-vitamin supplements seem encouraging, overall the results are far from conclusive [8?1]. Certain studies have even raised safety concerns with doses of vitamins C or E far above the recommended dietary intake [12?5]. The meta-analysis published by Jia et al actually concluded that antioxidant supplements in elders aged over 65 years have no beneficial effects on cognitive decline [16]. This failure may be partly explained by inadequate amounts or types of antioxidants or inappropriate timing of the supplementation. Drugs specifically prescribed for memory impairment such as nootropics and vasodilators represent obvious potential interventions to prevent cognitive decline. In France, Ginkgo biloba extract (EGb761H- TanakanH) has been marketed for more than thirty years as a medication for memory impairment and is marketed in the United States as a dietary supplement. While the probably most well-known effect of G. biloba extract is the protection ofGinkgo Biloba and Long-Term Cognitive Declineneuronal cell membranes from free radical damage [17], the properties of EGb761H go beyond that simple antioxidant mechanism. It has been shown to reduce Ab aggregation and toxicity [18,19], participate to mitochondrial protection [20] and promote hippocampal neurogenesis [21]. EGb761H has been also shown to decrease blood viscosity and enhance microperfusion [22]. Several studies on rats models also showed that EGb 761H improves neurotransmission, in particular glutamatergic [23], dopaminergic and cholinergic system [24,25]. Therefore, EGb761H can really be considered as a multi-target drug. Recent reviews and meta-analyses of randomised controlled trials concluded that EGb761H is effective in the treatment of patients with dementia, including Alzheimer’s disease, vascular dementia and mixed forms [26,27], in particular in demented patients with neuropsychiatric symptoms [27?0]. Regarding prevention, only one observational study carried out in a cohort of elderly women has so far suggested the beneficial effect of vasodilators, including G. biloba, in delaying the onset of dementia [31]. However, two clinical trials, i.e. the GEM (for Ginkgo Evaluation of Memory) study conducted in 3069 participants aged 75 and over with mild cognitive impairment [32] and the GuidAge study conducted in 2854 participants aged 70 and over and reporting memory complaints [33] failed to confirm such results. In these studies, G. biloba at 120 mg twice a day was not effective in reducing the overall incidence of dementia or Alzheimer’s disease. However, in both studies, as in another more limited feasibility trial [34], dementia was the main MedChemExpress PF-00299804 efficacy criteria and the follow-up period was relatively short (3.5 years in Dodge’s study ; 6.1 years in the GEM study ; 5 years in the GuidAge study). Due to the particularly long pre-dementia phase of Alzhei.R of interventional or observational studies have looked at the potential benefits of various pharmacological treatments. In particular, drugs controlling vascular factors such as statins have received much attention as a result of the growing emphasis on the vascular component of dementia and cognitive decline. However, these studies have yielded contrasting results [1?]. As the neurodegenerative process is accompanied by exacerbated oxidative stress, anti-oxidant vitamins have also been considered as good candidates [7]. Even if the results of the few studies reportingpotential benefits of vitamin E, beta-carotene or multi-vitamin supplements seem encouraging, overall the results are far from conclusive [8?1]. Certain studies have even raised safety concerns with doses of vitamins C or E far above the recommended dietary intake [12?5]. The meta-analysis published by Jia et al actually concluded that antioxidant supplements in elders aged over 65 years have no beneficial effects on cognitive decline [16]. This failure may be partly explained by inadequate amounts or types of antioxidants or inappropriate timing of the supplementation. Drugs specifically prescribed for memory impairment such as nootropics and vasodilators represent obvious potential interventions to prevent cognitive decline. In France, Ginkgo biloba extract (EGb761H- TanakanH) has been marketed for more than thirty years as a medication for memory impairment and is marketed in the United States as a dietary supplement. While the probably most well-known effect of G. biloba extract is the protection ofGinkgo Biloba and Long-Term Cognitive Declineneuronal cell membranes from free radical damage [17], the properties of EGb761H go beyond that simple antioxidant mechanism. It has been shown to reduce Ab aggregation and toxicity [18,19], participate to mitochondrial protection [20] and promote hippocampal neurogenesis [21]. EGb761H has been also shown to decrease blood viscosity and enhance microperfusion [22]. Several studies on rats models also showed that EGb 761H improves neurotransmission, in particular glutamatergic [23], dopaminergic and cholinergic system [24,25]. Therefore, EGb761H can really be considered as a multi-target drug. Recent reviews and meta-analyses of randomised controlled trials concluded that EGb761H is effective in the treatment of patients with dementia, including Alzheimer’s disease, vascular dementia and mixed forms [26,27], in particular in demented patients with neuropsychiatric symptoms [27?0]. Regarding prevention, only one observational study carried out in a cohort of elderly women has so far suggested the beneficial effect of vasodilators, including G. biloba, in delaying the onset of dementia [31]. However, two clinical trials, i.e. the GEM (for Ginkgo Evaluation of Memory) study conducted in 3069 participants aged 75 and over with mild cognitive impairment [32] and the GuidAge study conducted in 2854 participants aged 70 and over and reporting memory complaints [33] failed to confirm such results. In these studies, G. biloba at 120 mg twice a day was not effective in reducing the overall incidence of dementia or Alzheimer’s disease. However, in both studies, as in another more limited feasibility trial [34], dementia was the main efficacy criteria and the follow-up period was relatively short (3.5 years in Dodge’s study ; 6.1 years in the GEM study ; 5 years in the GuidAge study). Due to the particularly long pre-dementia phase of Alzhei.
