Jennifer Crumm

Michael Zemel
NTR 302-001
March 05, 2009
Ginkgo Biloba and Its Effects on Alzheimer's Disease

Alzheimer's disease is the most common form of dementia among the elderly

today'. 'While progress has been made in researching how Alzheimer's affects the brain

and the different treatments available for Alzheimer's patients, there is still so much more

to discover. To fully understand tIle severity of this disease, knowing how it affects the

brain and the different treatments available can give the patients and their caregiv:ers an

advantage in the fight to retain the memory of those affected. Alzheimer's disease attacks

the brain areas that control the memory and thinking skills. There are many treatments

available for Alzheimer's, both drug and non-drug methods. Each treatment has

promising results, but some methods are more effective than others. Unfortunately, with

rising costs in medication, it has become increasingly m.ore difficult to obtain

pharmaceutical treatments to prevent the progression of Alzheimer's. However, there are

a number of alternative treatments, for example, coenzyme Q 10, onlega-3 fatty acids, or

ginkgo biloba, that are popularly used as "memory enhancers or treatments for

Alzheimer's disease and related diseases" (1). For centuries, Ginkgo Biloba extract, or

GBE, was used in traditional Chinese medicine and is now used in Europe "to alleviate

cognitive symptoms associated with a number of neurological conditions" (1). Ginkgo

Biloba is risillg in popularity in the States, but many studies have been conducted to

challenge the effectiveness of GBE on dementia, such as Alzheimer's.

Deme~tia, which "literally means loss of mentation, or thinking" (2), is a group of

disorders that impair cognitive functions to which Alzheimer's is the most common.
~;\lzheimer's disease has a brief history. Discovered in 1906, it is also known as AD,

named after German doctor Alois Alzheimer who noticed changes in the brain tissue of a

woman who had died of an unusual mental illness (3). He found what are now considered

significant signs of AD. Along with symptoms of memory loss, language problems, and

unpredictable behavior, abnormal clumps, or amyloid plaques, and tangled bllndles of

fibers, or neurofibrillary tangles, were found in the elderly patient of Dr. Alzheimer (3).

Alzheimer's disease is progressive and irreversible and advances in stages, "progressing

from mild forgetfulness and cognitive impairment to widespread loss of mental abilities"

(2). Alzheimer's "[causes] problems with memory, thinking, and behavior severe enough

to affect work, lifelong hobbies or social life" (1). As Alzheimer's progresses, the

patient's memory, ability to learn, reason, make judgments, communicate and carry Ollt

daily activities becomes diminished. III addition, changes in personality and behavior, as

well as development of delusions or hallucinations, are common in AD patients (2). AD

advances at different rates for each patient. Recent estinlates figure "2.4 to 4.5 million

Americans are living with Alzheimer's disease" (3) and "about 360,000 people are newly

diagnosed each year" (2). On average, AD patients die four to six years after diagnosis.

As the disease progresses, the brain areas that control the memory and thinking skills are

affected first by the nerve cells shrinking and ultinlately dying. These cells include

neurotransmitters, a critical chemical messenger that relays brain signals from one nerve

cell to another (2; 3). The neurotransmitter Acetylcholine occurs in lesser amounts in

people with Alzheimer's. And, as these nerve cells disappear, the brain itself shrinks and

the syllapses, or "wrinkles", of the brain vanish, leaving a smoother surface (2). "By the

final stage of AD, damage is widespread and brain tissue has shrunk significantly" (3).
 Ginkgo Biloba extract is the most popular alternative medication for Alzheimer's.

The mechanisms by which Ginkgo biloba might help alleviate Alzheimer's symptoms

focus on it functions as a "neuroprotective agent" (4), an antioxidant, and the "possible

effects on amyloid metabolism" (5)0 The extract found in Ginkgo biloba extracts in

supplements sold worldwide is Ginkgo extract EGb 761. This extract contains two main

constituents, which are unique to Gir1kgo biloba trees: flavonoids and terpene lactone

(ginkgolides and bilobalide) (6). "The flavonoids and ginkgolides have protean biological

activity in preclinical research" (6). The flavol10ids appear to have antioxidant and

neuroprotective effects, where as the ginkgolides have multiple functions. There are three

ginkgolides of interest, A, B, and J. Ginkgolide B inhibits platelet-activating factors and

Ginkgolides A and J inhibits l1euron dysfunction and neural cell death by amyloids (6).

Ginkgolides A and J decrease the pathological behavior of amyloids, "enhance

neurogenesis in animal models of Alzheimer disease" (6), and prevent amyloids from

accumulating (6). The actions of Ginkgolides A and J provide convincing evidence for

Ginkgo biloba extract as a potential treatment for Alzheimer's disease. "Some of the

components of G biloba extract are as active in preclinical models of neurodegeneration

and Alzheimer disease as new drug candidates being developed" (6). However, the

biochemical properties of Ginkgo biloba may not be enough to provide consistent results

in clinical tests where GBE is the sole preventative medication for Alzheimer's. Many

studies have been done to evaluate the efficacy of Ginkgo biloba's in treating

Alzheimer's.

One specific study aimed to "assess the efficacy of the [GBE] in patients with

dementia of the Alzheimer type in slowing down the disease's degenerative progression
and the patient's cognitive impairment" (7). In this 24-week long randomized placebo­

controlled double-blind study, patients between the ages 50 and 80 years suffering from

mild to moderate dementia were given one of three treatments: Ginkgo biloba (160mg

daily dose), donepenzil (5mg daily dose), or a placebo (7). The degree of severity of

dementia was determined by "the Syndrom Kurz test (SKT), a psychometric test battery

for the assessment of memory and attention" (7). The patients in this study had mild to

moderate dementia, determined by a score between 8 and 23 on the SKT, and were

excluded from the study if they had "dementia of other etiology, severe organic diseases

(tumors, severe infectious diseases, brain trauma, epilepsy, cerebrovascular

malfoffilations, alcohol or drug abuse), pseudodementia or a history of schizophrenic or

affective psychoses" (7). Since much debate surrounds the efficacy of Ginkgo biloba

extract as treatment for Alzh~imer's, this study directly compared GBE to a

"cholinesterase inhibitor" (7) in an effort to provide more support for GBE. After the

completion of the study, the patients were administered the SKT once more. When

compared to the baseline results, the differences of SKT scores in the GBE and donepezil

groups showed that GBE "patients' attention and memory performance after 6 months of

treatment as measured by the SKT had shown significant improvements, comparable with

the results obtained by patients treated with donepezil" (7). The results of this study

confirmed that Ginkgo biloba has clinical efficacy comparable to that of donepezil in the

treatment of Alzheimer's. However promising this study is, many others have been

conducted that refute these results.

Over the past two decades, a number of studies have been conducted to assess the

efficacy ofGBE in treating Alzheimer's disease. One of the most convincing studies
declining the claims that GBE is an effective.treatment is the Ginkgo Evaluation of

Memory, "a randomized, double-blind trial sponsored by the National Center for

Complementary and Alternative Medicille (NCCAM) and the National Institute on Aging

of the National Institutes of Health (NIH)" (8). From 2000 to 2008, 3,069 volunteers age

75 years or older, 2,587 with normal cognitive function and 482 with mild cognitive

impairment, were assessed every 6 months for "incident dementia" (8). Participants were

excluded from the study if they "1) currently taking the anticoagulant warfarill; 2) taking

cholinesterase inhibitors for cognitive problems or dementia (memantine had not been

approved for use in the United States when the study began); 3) unwilling to discontinue

taking over-the-counter G biloba for the duration of the study; 4) currently being treated

with tricyclic antidepressants, antipsychotics, or other medications with sigIlificant

psychotropic or central cholinergic effects (the anticholinergic effects of selective

serotonin reuptake inhibitors were not believed to be substantial enough to warrant

exclusion); 5) daily use of more than 400-IU vitaminE or unwillingness to reduce intake

to this level; 6) history of bleeding disorders; 7) hospitalization for depression within the

last year or electroconvulsive therapy within last 10 years; 8) history of Parkinson disease

or taking anti-Parkinson medications; 9) abnormal thyroid tests, serum creatinine level

greater than 2.0 mg/dL (to convert to ~mol/L, multiply by 88.4), or liver function tests

more than 2 times the upper limit of normal at baseline; 10) baseline vitamin B 12 levels

210 pg/mL or lower (to COllvert to pmol/L, multiply by 0.7378); 11) hematocrit level less

than 30%; 12) platelet COlInt lower than 100 xl0 3/JlL; 13) disease-related life expectancy

of less than 5 years; or 14) known allergy to G biloba" (8). Twice daily, the volunteers

were administered either 120-mg of Ginkgo biloba extract or a placebo. Chosen

completel)! at random, 1,545 participants received the GBE dosage and the remaining

1~524 received the placebo. Throughollt the study, 532 participants were diagnosed with

dementia: 246 in the placebo group and 277 in the Ginkgo biloba group (8). In the GEM

Study with "3069 older adults with normal cognitive function or mild deficits, G bilaba

showed no benefit for reducing all-cause dementia or dementia of the Alzheimer type"

(8). Due to the large sample size from a population with increased risk of developing

dementia, the randomization in distributing the GBE dosage and placebo, and the

frequent cognitive tests to measure for any developing signs of dementia administered by

expert committees uninformed of the participant's group assignment (8), the results from

this study are viable and are strongly upheld by the medical field.

There is no identified cause of Alzheimer's disease and, unfortunately, no cure is

on the horizon. However, millions of dollars are financing research so that one day this

devastating disease will no longer be a death sentence. There are many treatments for

Alzheimer's disease, ranging from supplements to prescription drugs. The rising

popularity of Gil1kgO biloba, with its history as a promoter of cognitive function, led to

studies that challenged its efficacy as an Alzheimer's treatment. In the debate between

cholinesterase inhibitors, such as donepezil, and Ginkgo biloba as treatments, evidence

points to pharmaceutical treatments as the most effective way to prevent and delay the

developing symptoms of Alzheimer's. G-inkgo biloba certainly is more affordable than

prescription drugs but it is lacking in evidence to promote it as a treatment for

Alzheimer's; and when it comes to prolonging the memory, personality, and life of those

afflicted with the disease, it is often best to choose the treatment that has proven itself

effective.
 References

1. Alzheimer's Association. 27 Feb 2009.2 Mar 2009. <http://alz.org/index.asp>.

2. "What is Alzheimer's Disease." Fisher Center for Alzheimer's Research

Foundation. 2 Mar 2009. <http://www.alzinfo.org/alzheimers-disease­

inforrnation.asp#1>.

3. "Alzheimer's Disease Fact Sheet." U.S. National Institutes of Health- Nation

Institute on Aging. 24 Feb 2009. 2 Mar 2009.

<http://www.nia.nih.gov/AlzheimerslPublications/adfact.htm>.

4. Blumenthal, Mark, Victor S. Sierpina, and Bernd Wallschlaeger. "Ginkgo Biloba."

American Family Physician. 1 Sept 2003. PubMed. 24 Jan 2009.

<http://www.aafp.org/afp/20030901/923.html>.

5. Furberg, Curt D. and Steven T. DeKonsky. "Turning over a new leaf: Ginkgo

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PubMed. 24 Jan 2009.

<http://www.neurology.org/cgi/content/fulVneurology;70/19_Part_2/1809?co

okietest=yes>.

6. Schneider, Lon S. "Ginkgo biloba Extract and Preventing Alzheimer Disease."

JAMA 2008; 300 (19): 2306-2308. PubMed. 24 Jan 2009. <http://jama.ama­

assn.org/cgi/content/full/300/19/2306#REF-JED80067-15#REF-JED80067­

15>.

7. Bria, P., A Capuano, M. Mazza, and S. Mazza. "Ginkgo biloba and donepezil: a

comparison in the treatment of Alzheimer's dementia in a randomized

placebo-controlled double-blind study." European Journal of Neurology. 13.9

~)<~
II ~--!/
 (2006): 981-985. PubMed.

<http://www3.interscience.wiley.com.cgi_bin/fulltext/118554705/main.html,f

tx abs#b4#b4>.

8. DeKonsky, Steven T., et aL "Ginkgo biloba for Prevention of Dementia." JAMA

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47>.