Jennifer Crumm Michael Zemel Ntr 302-001 March 05, 2009
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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.. 2. "What is Alzheimer's Disease." Fisher Center for Alzheimer's Research Foundation.
2
Mar
2009.
inforrnation.asp#1>. 3. "Alzheimer's Disease Fact Sheet." U.S. National Institutes of Health- Nation Institute
on
Aging.
24
Feb
2009.
Mar
2
2009.
. 4. Blumenthal, Mark, Victor S. Sierpina, and Bernd Wallschlaeger. "Ginkgo Biloba." American Family Physician.
1 Sept 2003. PubMed. 24 Jan 2009.
. 5. Furberg, Curt D. and Steven T. DeKonsky. "Turning over a new leaf: Ginkgo biloba in prevention of dementia." NEUROLOGY 2008; 70: 1730-1731. PubMed.
24
2009.
Jan
. 6. Schneider, Lon S. "Ginkgo biloba Extract and Preventing Alzheimer Disease." JAMA 2008; 300 (19): 2306-2308. PubMed. 24 Jan 2009. . 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.
. 8. DeKonsky, Steven T., et aL "Ginkgo biloba for Prevention of Dementia." JAMA 2008; 300(19): 2253-2262. PubMed. 24 Jan 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.
2
Mar
2009.
inforrnation.asp#1>. 3. "Alzheimer's Disease Fact Sheet." U.S. National Institutes of Health- Nation Institute
on
Aging.
24
Feb
2009.
Mar
2
2009.
1 Sept 2003. PubMed. 24 Jan 2009.
24
2009.
Jan
~)<~ II
~--!/
(2006):
981-985.
PubMed.
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