Ginkgo biloba for prevention/delay of cognitive impairment
Abstract & Commentary
By Donal O'Mathuna, PhD
Source: Dodge HH, et al. A randomized placebo-controlled trial of Ginkgo biloba for the prevention of cognitive decline. Neurology. 2008;70:1809-1817.
The objective of this study was to assess the feasibility, safety, and efficacy of Ginkgo biloba extract (GBE) on delaying the progression to cognitive impairment in normal elderly subjects aged 85 and older.
Methods: Randomized, placebo-controlled, double-blind, 42-month pilot study with 118 cognitively-intact subjects randomized to standardized GBE or placebo. Kaplan-Meier estimation, Cox proportional hazard, and random-effects models were used to compare the risk of progression from Clinical Dementia Rating (CDR) = 0 to CDR = 0.5 and decline in episodic memory function between GBE and placebo groups.
Results: In the intention-to-treat analysis, there was no reduced risk of progression to CDR = 0.5 (log-rank test, P = 0.06) among the GBE group. There was no less of a decline in memory function among the GBE group (P = 0.05). In the secondary analysis, where we controlled the medication adherence level, the GBE group had a lower risk of progression from CDR = 0 to CDR = 0.5 (HR = 0.33, P = 0.02), and a smaller decline in memory scores (P = 0.04). There were more ischemic strokes and TIAs in the GBE group (P = 0.01).
Conclusion: In unadjusted analyses, Ginkgo biloba extract (GBE) neither altered the risk of progression from normal to Clinical Dementia Rating (CDR) = 0.5 nor protected against a decline in memory function. Secondary analysis, taking into account medication adherence, showed a protective effect of GBE on the progression to CDR = 0.5 and memory decline. Results of larger prevention trials, taking into account medication adherence, may clarify the effectiveness of GBE. More stroke and TIA cases observed among the GBE group requires further study to confirm.
Commentary
The rapidly growing number and proportion of older adults is creating a number of challenges for society. Given that women tend to live longer than men, these challenges are particularly important for women's health. One such challenge is the decline in cognitive capacity that comes with a number of illnesses impacting the elderly. A safe intervention that slows cognitive deterioration would be of great benefit in dementia prevention strategies. Extracts of Gingko biloba are widely used to prevent memory deterioration and treat Alzheimer disease.1
The population chosen to study in this trial was a group at high risk of developing dementia. Fifty percent of those with dementia in developed countries are over 80 years old. The participants were 85 years or older and began the trial with no subjective memory complaints and normal memory function, as measured by validated instruments. The study administered treatment or placebo for up to 42 months. This is appropriately long-term given that dementia prevention strategies would be pursued for several years. This also gave sufficient time for significant differences between the groups to become visible. The ginkgo samples used in the study were independently tested to ensure they contained appropriate amounts of active ingredients.
The primary analysis found no statistically significant delay in the progression to cognitive impairment using the Clinical Dementia Rating scale in those taking ginkgo compared to placebo. Similarly, the decline in memory function did not differ significantly between the two groups. The authors concluded that the relatively small sample size contributed to their inability to detect significant differences. They calculated that they would need a sample size of 2800 to detect a 20% reduction in risk of progression to cognitive impairment by the ginkgo extract. Two of the largest dementia primary prevention trials to be conducted are currently underway to examine the effectiveness of Ginkgo biloba extracts.1,2 Both are hoping to enroll approximately 3000 participants each, one in the United States and one in France.
A secondary analysis was also conducted to control different confounding variables; medication adherence is an important factor in studies of cognitive functioning. If participants' memory declines during the study, adherence to the study medication would decrease, which would impact the outcomes of the study. In the secondary statistical analysis, the researchers controlled for baseline medication adherence levels. Under these conditions, they calculated that the group taking ginkgo had a significantly lower risk of progressing to cognitive impairment, as well as less decline in memory function. These findings do not demonstrate that ginkgo is effective, but point to the importance of taking medication adherence into account in conducting further trials of ginkgo.
Another objective of this study was to examine the safety of gingko. Bleeding-related complications have been reported for ginkgo, but none were found in this study. A range of adverse effects was reported both by those taking ginkgo and those taking placebo. In only one category was there a significant difference between the groups. Six cases of stroke and one case of transient ischemic attack (TIA) were reported in the ginkgo group compared to none in the placebo group. The difference was statistically significant and calls for careful study in future trials.
The authors of this study believe that theirs is the first dementia prevention, randomized, controlled trial conducted with the "oldest old" participants (those over 80). They demonstrated that such a study is feasible and can produce valuable information. This is particularly important given that this population is projected to increase in numbers in the coming years. This study shows that this population should not be excluded from trials based on preconceived notions of frailty or confounding health problems.
References
1. Vellas B, et al. The GuidAge study: methodological issues. A 5-year double-blind randomized trial of the efficacy of EGb 761 for prevention of Alzheimer disease in patients over 70 with a memory complaint. Neurology. 2006;67:S6-S11.
2. DeKosky ST, et al. The Ginkgo Evaluation of Memory (GEM) study: design and baseline data of a randomized trial of Ginkgo biloba extract in prevention of dementia. Contemp Clin Trials. 2006;27:238-253.
The objective of this study was to assess the feasibility, safety, and efficacy of Ginkgo biloba extract (GBE) on delaying the progression to cognitive impairment in normal elderly subjects aged 85 and older.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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