ArticlesLong-term use of standardised ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): a randomised placebo-controlled trial
Introduction
Prevalence of Alzheimer's disease is expected to quadruple by 2050.1, 2 A preventive intervention that delays disease onset by a few years could greatly reduce the burden of this disease on society and health-care systems,3, 4 as has been achieved in other chronic conditions.5
Few randomised trials have tested the efficacy of an intervention for the reduction of dementia incidence.6, 7, 8, 9, 10 The shortage of such trials might partly be explained by numerous methodological challenges, including the need for an excellent safety profile because large numbers of healthy participants will receive the intervention for a long time, only a few of whom will develop dementia. Drugs investigated so far for either primary or secondary prevention of Alzheimer's disease include hormone replacement therapy, non-steroidal anti-inflammatory drugs, ginkgo biloba extract, vitamin supplements, and cholinesterase inhibitors. All have either failed to show efficacy or have been associated with safety concerns.11, 12
Standardised ginkgo biloba extract is widely used in some countries by patients with cognitive disorders (eg, memory decline with ageing and Alzheimer's disease),13 and observational research suggests that it might prevent Alzheimer's disease.14 Plausible mechanisms of action against Alzheimer's disease include powerful antioxidant effects15, 16 and potential inhibition of caspase-3 activation and amyloid-β aggregation.17 Standardised ginkgo biloba extract has a good safety profile, although some case reports have suggested an increased risk of bleeding.18
Subjective memory complaints in elderly individuals, especially if spontaneously expressed to a doctor,19 are associated with an increased risk of dementia,20 and have been linked to brain atrophy and amyloid-β deposition.21 Therefore, some individuals who present to their doctors with such complaints might be in an early stage of mild cognitive impairment, and could thus be a target population for interventions aimed at prevention of Alzheimer's disease. This population could be identified by primary health-care systems, thus enabling creation of large-scale public health prevention programmes for Alzheimer's disease.
In the GuidAge study, we aimed to assess the efficacy of standardised ginkgo biloba extract for reduction of the risk of conversion to Alzheimer's disease in elderly individuals spontaneously reporting memory complaints to their primary-care physician (PCP).
Section snippets
Study design and participants
The protocol for our multicentre, randomised, double-blind, placebo-controlled, parallel-group, 5 year study has been published previously,22 and was approved by the Independent Ethics Committee of Toulouse University Hospital, Toulouse, France. Participants were recruited throughout France from March, 2002, to November, 2004, by 712 PCPs belonging to clinical research networks (Isoclin, EURAXI Pharma, MG Recherche, and PROCLINICA) or by staff at one of the 25 memory centres participating in
Results
Figure 1 shows the trial profile and table 1 shows baseline characteristics for the 2820 patients who received at least one dose of study drug or placebo.
2835 (99%) of 2854 eligible participants were recruited by a PCP, and 19 were recruited by a memory centre. Compared with included participants, individuals who refused to participate were older (mean 77·8 years [SD 5·2] for non-participants vs 76·3 years [4·4] for participants; p<0·0001), had lower MMSE scores (27·3 [1·8] vs 27·8 [1·7];
Discussion
Effective and safe prevention strategies are urgently needed to tackle the growing public health burden of Alzheimer's disease, and the efficacy of any such intervention needs to be shown through randomised controlled trials. GuidAge is only the third dementia prevention trial to be completed and is the first to be done outside of the USA (panel). We aimed to assess the efficacy of 5 years' administration of a standardised ginkgo biloba extract, which is widely used by patients with cognitive
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