Dementia, also referred to as major neurocognitive disorder (including Alzheimer disease [AD]), is a growing problem because of increased lifespan. There is no known cure. Several drugs are FDA-approved for the treatment of dementia, including acetylcholinesterase inhibitors (eg, donepezil, rivastigmine, galantamine) and an N-methyl-D-aspartate (NMDA) receptor antagonist, but these have limited efficacy, adverse effects, and significant cost—all of which contribute to the search for alternative therapies to improve cognition.
In this article, we look at several natural products used to improve cognitive impairment or cognitive symptoms of dementia (Table).
A popular supplement for cognition is ginkgo biloba, which is extracted from the leaf of the Maidenhair tree. Although it has been used as a supplement in the US, in many European countries it is part of mainstream medical care and requires a prescription. A standardized extract called EGb 761 is prescribed in many countries outside of the US.
Nash and Shah1 examined the mechanisms of ginkgo biloba that provide neurocognitive benefits and defined its 3 main active agents: ginkgolides, bilobalide, and flavonoids. The ginkgolides are thought to inhibit platelet-activating factor, thereby preventing clotting, promoting blood flow, and inhibiting inflammatory mediators such as cyclooxygenase-2, nitric oxide synthase, and tumor necrosis factor. Bilobalide is thought to inhibit platelet-activating factor receptors and
reduce the excitotoxic effects of glutamate. Finally, the flavonoids serve as antioxidants that reduce the damage caused by free radicals.
The majority of trials that show the benefits of ginkgo biloba pertain to improved cognition in persons who already have a major neurocognitive disorder or dementia. However, the data regarding a benefit in cognitively intact individuals are mixed. The most rigorous study by Mix and Crews2 examined the effect of a 180-mg dose of ginkgo biloba on community-dwelling individuals without neurocognitive disorders. Full neuropsychological testing showed some small improvements in memory, but intergroup differences limited the results. The dosage was lower than typically recommended, which is generally about 120 mg to 240 mg, 2 or 3 times daily. Another randomized clinical trial (RCT), which used a 240-mg dose of ginkgo biloba, demonstrated some small effects in immediate and delayed recall.3 In summary, there is no compelling evidence to support the use of ginkgo biloba to improve memory functioning in individuals who are cognitively intact.
Can ginkgo biloba prevent major neurocognitive impairment? Four well-designed studies show differing results. The Ginkgo Evaluation of Memory (GEM) study examined more than 3000 individuals aged over 75 years with either normal cognition or mild cognitive impairment.4 The study failed to show any protective effect of ginkgo biloba in preventing dementia.
Another study looked at the prevention of AD in adults aged 72 to 96 years with either normal cognition or mild cognitive impairment.5 The study used EGb 761 (a ginkgo biloba extract) at a dosage of 120 mg twice daily over the course of 6 years. No risk reduction was found.
The GuidAge study looked at the prevention of dementia with ginkgo biloba in more than 2000 community-dwelling older adults over a 5-year period.6 Like the GEM study, the GuidAge study did not show a benefit of ginkgo biloba in preventing dementia over 4 years; however, after 5 years, it started to show an improvement. A limitation of the GuidAge study is the especially low incidence of dementia in the participant population (1.2/100 to 1.4/100), which makes it more difficult to show statistical significance. The large, 20-year PAQUID study showed that ginkgo biloba prevented dementia. However, important characteristics such as dosage and duration of ginkgo treatment were not documented.7
Dr. Varteresian is MH Psychiatrist, Los Angeles County Department of Mental Health, and Assistant Clinical Professor (volunteer) at the University of California, Irvine. Dr. Lavretsky is Professor of Psychiatry at the University of California, Los Angeles (UCLA) and Director of the Late-Life Mood, Stress, and Wellness Research Program at the Semel Institute for Neuroscience and Human Behavior, Geffen School of Medicine at UCLA. Dr. Varteresian reports no conflicts of interest concerning the subject matter of this article; Dr. Lavretsky reports that she is a recipient of grants from Forest Research Institute/Actavis and the NICCIN and NIMH.
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