National Alzheimers Disease Institute

 

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Ginkgo Helps to Prevent or Slow Down Alzheimer’s Disease

P. Anthony Chapdelaine, Jr., MD, MSPH, Exec. Dir./Sec.*

 

Below is a sample of well-done meta-analyses and double-blind, placebo-controlled, multi-center trials evaluating the use of Ginkgo biloba extract in delaying the progression, or improving the symptoms, of patients with AD. (Some of these trials also include patients with multi-infarct dementia who were helped by using Ginkgo biloba.).

As you will read, Ginkgo has been shown time after time to help patients who have already been diagnosed with AD, and in some cases, with multi-infarct dementia.

There have been no long-term (those lasting over a decade) studies that used Ginkgo (while also measuring the exposure to environmental toxins or the use of vitamin/herbal interventions) to see whether this substance can also prevent AD, or help with cognitive reserve, and thus clinically prevent AD. Based on the proven efficacy of Ginkgo in helping with the symptoms of mild to advanced AD, we should expect it to have a significant clinical role in helping prevent AD as well.

Problems with the Ginkgo Evaluation of Memory (GEM) Study

Misinformation about Ginkgo is common, even among governmental groups whose researchers should know better. This is unfortunate.

“Ginkgo Evaluation of Memory (GEM) Study Fails to Show Benefit in Preventing Dementia in the Elderly” is the title for the NIH’s summary of a very expensive ($37 million) study in which the average participant age at the beginning of the study was 79 years-old.1 This title shows the apparent bias of the NIH toward using or encouraging simplistic studies using poorly defined surrogates for complex medical consequences. The study’s results do not support the NIH or researchers’ conclusions, and thus demonstrates that the NIH typically fails to adequately analyze, or takes-for-granted the ill-informed conclusions of, studies that don’t actually show what the study researchers say they show.

For this “study” (in which they tried to do several studies at one time, which introduces a large degree of complexity and uncertainty) some participants were considered “normal” and some were diagnosed with mild cognitive loss. Every six months for an average of six years, the participant or a person (family etc) familiar with the participant was interviewed and these responses were evaluated by an “expert panel” that decided whether or not the participant showed signs of dementia (AD). The participants were randomly, blindly assigned to take ginkgo extract or placebo.

There are many problems with this study.

These were elderly people who did not survive long-enough to determine whether long-term ginkgo (perhaps along with other natural interventions that have already been shown to diminish or prevent AD) would have slowed or eliminated AD development or progression. This study cannot answer that question. Over such a relatively short study-period, and especially for already very elderly participants, one cannot expect any intervention, drug, or natural ingredient to clinically alter the progression of a chronic condition that develops over a lifetime of environmental (and for a small percentage, genetic) toxic exposures. We know that long-term environmental exposures require long-term (perhaps decades) interventions to ameliorate the risk of dementia through the use of substances such as ginkgo.

The study only used MRIs to examine the brains of participants diagnosed by an “expert panel” with symptoms suggesting AD. Those without this “diagnosis” (normal participants) did not get an MRI. Those participants who did not get the “expert panel” agreed-upon diagnosis of “dementia” did not have an MRI. Yet, it has been shown elsewhere that a small percentage of “normal” brains at autopsy show pathological findings that would typically be diagnosed as evidence of Alzheimer’s Disease. Because the “normal” people were not examined by MRI, this very expensive study cannot say whether ginkgo prevented or minimized AD symptoms in the people considered “normal” (perhaps by enhancing the person’s “cognitive reserve” as described below).

We also know that by the end of this study forty percent of participants were not taking the ginkgo. Therefore, this study cannot even tell us whether the nearly-half of participants who did not take the ginkgo for the entire study period would have benefited if only they had taken it.

This “study” appears to have been a waste of taxpayer money, at least as regards the study of Ginkgo!

NIH Funded a Pilot Study That Showed Improvement in Those Who Take Ginkgo

Contrary to the conclusion of the GEM study referenced above, this study, funded and referenced by the NIH, showed that when you look at those who actually took the ginkgo (not just whether they were supposed to, but maybe didn’t) showed a clinically significant decrease in the progression of AD.2

“This small study funded by the National Institute on Aging and NCCAM and led by Hiroko Dodge, Ph.D., and colleagues at the Oregon Health & Science University and the Oregon State University, followed 118 volunteers age 85 or older over the course of 42 months.”

Even in this elderly group, who didn’t start the ginkgo until many years after the AD had already established (from environmental causes mostly) itself, ginkgo showed it could halt or slow the progression of the cognitive decline.

“Overall, in a pilot study of a ginkgo biloba extract for delaying the onset of dementia in the elderly, researchers did not find a reduction in progression to dementia in those using ginkgo versus those using placebo. However, when the researchers took into account participants’ adherence to taking the compound, the group that took ginkgo did appear to have a reduced risk of progression and a smaller decline in memory.” [Emphasis added.]

Cognitive Reserve (Which Ginkgo Enhances) Helps to Explain Why Some People with AD Show Few or No Symptoms

A landmark analysis conducted by SantaCruz and his team of two long-term studies involving elderly people with or without evidence of dementia, whose brains were autopsied, showed that there are a significant number of people who show no, or minimal, cognitive decline before death, but nonetheless have brains that show the typical degeneration and “tangles” that would normally (pathologically) would have diagnosed them as having Alzheimer’s Disease.3

The researchers concluded that that these people (with brain degeneration, but no significant signs or symptoms of AD) had developed what is called “cognitive reserve,” meaning that over the years they had engaged in mental activities that prevented cognitive decline. They read books, played games, engaged in social functions and thus stimulated their brains to form new and additional neuronal networks, much as some stroke victims can regain most or all of their previous functions by creating, or utilizing, alternative nerve pathways in the brain to compensate for loss in other areas.

In a different analysis, Stern’s review of his group of researcher’s extensive experience with AD patients gave a theoretical basis for why cognitive reserve enabled some people to compensate (and thus show minimal cognitive decline) for the same brain degeneration (tangles and plaques) that are the hallmark of AD and which normally result in severe loss of cognition4:

“Several prospective studies of aging have reported that up to 25% of elders whose neuropsychological testing is unimpaired prior to death meet full pathologic criteria for Alzheimer’s disease. . .suggesting that this degree of pathology does not invariably result in clinical dementia. . .Many studies indicate that a set of life experiences such as educational and occupational exposure and leisure activities are associated with reduced risk of developing dementia and with a slower rate of memory decline in normal aging.”

Stern proposed that future studies need to measure cognitive reserve (CR) through imaging (eg, MRIs) to better evaluate outcomes from interventions:

“Imaging could be used as a meaningful outcome in cognitive interventions. Imaging CR would also be very useful for understanding any aged individual’s true clinical status, which would be a combination of underlying age-related (or Alzheimer’s disease-related) brain changes and that individuals’ CR in the face of those changes. Two individuals who appear the same clinically could differ widely on these underlying measures. This approach to characterizing clinical severity would have strong implications for prognosis and treatment.”

Finally, Stern concludes that “the epidemiologic evidence suggests that a set of lifetime exposures translates into a cognitive reserve that mediates the brain changes associated with aging or AD.”

Consistently, most researchers have found that whether someone will acquire AD depends on a large number of variables, which have yet to be adequately determined, much less studied. The concept of cognitive reserve complicates our understanding of the conclusions we can draw from most of the published studies claiming to “answer” the questions about prevention, diminished progression, or amelioration of AD. Those studies give conclusions based on inadequate or faulty study designs, do not consider cognitive reserve, examine AD progression through surrogates by infrequent interviews over relatively short study periods, use “expert panels” to give an opinion on whether someone has AD, and rarely include in their study designs the many environmental exposures that can lead to dementia, including AD.

Areas needing further research include all the NIH supported or endorsed studies on “natural” interventions to prevent or halt the progression of AD. New research will need better study designs and researchers more familiar with the complex field of nutrition, vitamins, and herbs.

Don’t rely on the currently NIH sponsored studies for planning your own natural interventions. Those studies simply aren’t good enough, yet, for that purpose.

Ginkgo biloba Helps with Positive Symptoms of Schizophrenia and Helps with Dementia

In contrast to the previously described, expensive, poorly-conceived study claiming that ginkgo shows no evidence of helping prevent AD in the elderly1, a review and meta-analysis by Brondino et al came to a very different conclusion5:

“We conducted a systematic review and a meta-analysis of three randomised controlled trials in patients with schizophrenia and eight randomised controlled trials in patients with dementia. Gb [Ginkgo biloba] treatment reduced positive symptoms in patients with schizophrenia and improved cognitive function and activities of daily living in patients with dementia.”

Ginkgo biloba 761 Extract Helps both Alzheimer’s Disease and Multi-infarct Dementia

In a seven month “prospective, randomized, double-blind, placebo-controlled, multi-center study” by Kanowski and team, over 200 people diagnosed with either mild to moderate Alzheimer’s Disease or multi-infarct dementia were given an extract of Ginkgo biloba or placebo.6

Efficacy of Ginkgo was assessed by requiring Improvement in at least two of the three primary study variables: psychopathological assessment, assessment of the patient’s attention and memory, and behavioral assessment of activities of daily life.

For both multi-infarct dementia and AD, only those taking ginkgo showed significant improvement. “Thus, the clinical efficacy of the ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type and multi-infarct dementia was confirmed.”

Another study at the same time as the Kanowski group (1996), by Le Bars and team, studied mild to severe AD patients or patients with multi-infarct dementia.7 This was “a 52-week, randomized double-blind, placebo-controlled, parallel-group, multicenter study” in which patients were randomized to 120 mg daily of EGb 761 or placebo. They were monitored for compliance, drug dispensation, and safety every three months, and given full evaluations at 12, 26, and 52 weeks.

Even for this group, which included severe AD and multi-infarct dementia conducted over such a short time period, Le Bars and team concluded that, “[Ginkgo biloba] EGb was safe and appears capable of stabilizing and, in a substantial number of cases, improving the cognitive performance and the social functioning of demented patients for 6 months to 1 year.”

Ginkgo biloba helps Alzheimer’s Disease

Almost two decades later (2014), Gauthier and Schlaefke conducted a review and meta-analysis of “seven of 15 randomized, placebo-controlled trials in patients with dementia identified by database searches8. . . .In these trials, [over 2,600 outpatients] were treated with 120 mg or 240 mg per day [for about four months] of the defined extract EGb 761 or placebo. Efficacy was assessed using validated tests and rating scales for the cognitive domain, the functional domain (activities of daily living), and global assessment.”

They came to the same conclusions as both the Kanowski team and the Le Bars team: “Statistically significant superiority of EGb 761 over placebo was confirmed by responder analyses as well as for patients suffering from dementia with neuropsychiatric symptoms. . . In conclusion, meta-analyses confirmed the efficacy and good tolerability of Ginkgo biloba extract EGb 761 in patients with dementia.”

 

* The National Alzheimer’s Disease Institute is a project of The National Fund for Alternative Medicine

References/Sources

  1. DeKosky ST, Williamson JD, et al, “Ginkgo bilobafor Prevention of Dementia,” Journal of the American Medical Association, 2008, 300(19), Pgs. 2253–2262.
  2. Dodge HH, et al, “A Randomized Placebo-Controlled Trial of Ginkgo Biloba for the Prevention of Cognitive Decline,” Neurology, 2008 May, 70(19 Pt 2), Pgs. 1809-1817, doi: 10.1212/01.wnl.0000303814.13509.db.
  3. SantaCruz KS, et al, “Alzheimer Disease Pathology in Subjects Without Dementia in Two Studies of Aging: The Nun Study and the Adult Changes in Thought Study,” J Neuropathol Exp Neurol, 2011 Oct, 70(10), Pgs. 832–840, doi: 10.1097/NEN.0b013e31822e8ae9.
  4. Stern Y, “Cognitive Reserve,” Neuropsychologia, 2009 Aug, 47(10), Pgs. 2015–2028, doi: 10.1016/j.neuropsychologia.2009.03.004.
  5. Brondino N, De Silvestri A, et al, “A Systematic Review and Meta-Analysis of Ginkgo biloba in Neuropsychiatric Disorders: From Ancient Tradition to Modern-Day Medicine,” Evidence-Based Complementary and Alternative Medicine, 2013, volume 2013, Article ID 915691, 11 pages, http://dx.doi.org/10.1155/2013/915691.
  6. Kanowski S, et al, “Proof of Efficacy of the Ginkgo biloba Special Extract EGb 761 in Outpatients Suffering from Mild to Moderate Primary Degenerative Dementia of the Alzheimer Type or Multi-infarct Dementia, Pharmacopsychiatry,1996 Mar, 29(2), Pgs. 47-56.
  7. Le Bars PL, et al, “A Placebo-controlled, Double-blind, Randomized Trial of an Extract of Ginkgo biloba for Dementia. North American EGb Study Group,” JAMA, 1997 Oct, 278(16), Pgs. 1327-1332.
  8. Gauthier S, Schlaefke S, “Efficacy and Tolerability of Ginkgo Biloba Extract EGb 761® in Dementia: A Systematic Review and Meta-analysis of Randomized Placebo-controlled Trials,” Clin Interv Aging,2014, 9, Pgs. 2065-2077, doi: 10.2147/CIA.S72728.