Falls May be Early Signs of Alzheimer's
Falls and balance problems may be early indicators of Alzheimer’s disease, according to a report presesented at the Alzheimer’s Association International Conference on Alzheimer’s Disease in Paris. Researchers at Washington University School of Medicine in St. Louis found that people with brain changes suggestive of early Alzheimer’s disease were more likely to fall than those whose brains did not show the same changes. Until now, falls had only been associated with Alzheimer’s in the late stages of dementia.
“If you meet these people on the street, they appear healthy and have no obvious cognitive problems,” says lead author Susan Stark, PhD, assistant professor of occupational therapy and neurology. “But they have changes in their brain that look similar to Alzheimer’s disease, and they have twice the typical annual rate of falls for their age group.”
Stark and her colleagues recruited 119 volunteers from studies of aging and health at Washington University’s Knight Alzheimer’s Disease Research Center. All the participants were 65 or older and cognitively normal.
Brain scans showed that 18 participants had high levels of amyloid plaques, a hallmark of Alzheimer’s. The other 101 volunteers had normal amyloid levels in the brain.
Participants were given a journal and asked to note any falls. When they did so, the researchers followed up with a questionnaire and a phone interview about the falls. This follow-up allowed researchers to gather information for future analyses that will compare and contrast the nature of the falls.
About one in three adults age 65 or older typically fall each year. But in the 18 participants with high amyloid levels in the brain, two-thirds fell within the first eight months of the study. High levels of amyloid in the brain were the best predictor of an increased risk of falls.
“Falls are a serious health concern for older adults,” Stark says. “Our study points to the notion that we may need to consider preclinical Alzheimer’s disease as a potential cause.”
Source: Washington University School of Medicine (2011, July 19). Falls may be early sign of Alzheimer's. ScienceDaily.
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Chinese Club Moss Extract (Huperzine A) May Improve Cognition In Alzheimer’s Disease
Existing evidence suggests that patients with Alzheimer’s disease who have taken Huperzine A have improved general cognitive function, global clinical status, functional performance and reduced behavioural disturbance compared to patients taking placebos.
The research team came to this conclusion after studying data in six trials that involve a total of 454 patients.
Part of the damage involved in Alzheimer’s disease is a loss of acetylcholine-containing neurons in the basal forebrain. This suggests that drugs that could inhibit cholinesterase, which breaks down acetylcholine, could increase the ability of remaining cholinergic neurons.
Scientists know that Huperzine A can block acetyl cholinesterase and that it can work both in the peripheral and central nervous systems. This makes it a promising agent for treating various forms of dementia including Alzheimer’s disease.
“These findings are based on small number of trials, but the data indicate that it would be well worth setting up some more high quality assessments of this interesting drug,” says Associate Professor Hongmei Wu, who led this research and works in the Department of Geriatrics at the West China Hospital of Sichuan University in Chengdu, Sichuan, China.
Source: Wiley-Blackwell (2008, April 17). Chinese Club Moss Extract (Huperzine A) May Improve Cognition In Alzheimer’s Disease.
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Huperzine-A Shows Promise for Enhancing Memory and Protecting Cognitive Functions
by Jim English
Alzheimer’s Disease (AD) is a progressive degenerative disease that most commonly appears after the age of 50. Currently, Alzheimer’s afflicts approximately 40% of all individuals over the age of 85, for a total of 4 million people in the U.S. alone. When symptoms occur before the age of 65 the disease is designated Presenile Dementia of the Alzheimer’s Type (PDAT). When symptoms occur after age 65 the syndrome is referred to as Senile Dementia of the Alzheimer’s Type (SDAT). Symptoms include a gradual yet inexorable loss of memory, mental performance, communication skills, abstract thinking and personality. Ultimately, Alzheimer’s ends in the death of the patient, with a mean life expectancy of 8 years.
As well as being a profound personal tragedy for afflicted individuals and their loved ones, the financial costs of caring for victims of the disease exceed $80 billion per year. The current trend towards longer life expectancy, combined with the increased incidence of senile dementia with age, means that cases of Alzheimer’s increase alarmingly as the median age of the population grows, underscoring the urgency for finding an effective treatment for this disorder.
Huperzine-A is a new supplement derived from an ancient traditional Chinese herbal medicine that offers hope to those suffering from Alzheimer’s disease and other age-related mental conditions. In addition to benefiting patients suffering from Alzheimer’s, Huperzine’s memory-enhancing properties suggest that it may be an effective agent for improving memory and learning in healthy humans as well.
Cholinergic Dysfunction in Alzheimer’s
Alzheimer’s is characterized by the destruction of nerve cells in several key areas of the brain devoted to mental functions. This results in tangles of nerve fibers and plaque formation of an abnormal, insoluble protein called amyloid. While there is a general reduction in the concentration of all neurotransmitting substances, a marked clinical feature of the disease is a dramatic decrease in the neurotransmitter acetylcholine.
Acetylcholine is a vital neurotransmitter with a fundamental role in memory. It is also necessary for proper intracellular communication between nerve cells. Research has shown that levels of acetylcholine are deficient in the brains of patients with Alzheimer's disease.
Biopsy and postmortem studies have shown that there is a substantial loss of presynaptic cholinergic neurons in brains of patients with Alzheimer’s.(1) What little acetylcholine that is still produced in the patient’s brain is quickly broken down by the brain enzyme, acetylcholinesterase (AchE), leading to a shortage of the neurotransmitter and contributing to the patient’s loss of memory and other cognitive functions.
Prescription Alzheimer’s Drugs
Two drugs are currently approved for use in the U.S. to treat Alzheimer's – Tacrine™ and Donepezil hydrochloride (Aricept™). Both drugs are moderately effective cholinesterase inhibitors that work by interfering with the actions of AChE. Since acetylcholine is normally degraded and recycled by acetylcholinesterase, this approach counteracts any further reduction of already low levels of acetylcholine.
By inhibiting the actions of AChE it is hoped that the small amounts of acetylcholine still being produced will persist longer within the synaptic cleft and lead to improvements in memory and cognitive abilities. While both drugs are effective cholinesterase inhibitors, they suffer from a number of drawbacks. First, they are available only by prescription; second, they are expensive, costing between $100 - $240 per month; and third, both drugs can cause debilitating side effects including liver toxicity (Tacrine), and nausea and diarrhea (Donepezil).(1)
Huperzine A: A Safe Alternative
Huperzine A is a natural compound derived from an ancient Chinese remedy, Qian Ceng Ta. This traditional herbal medicine was prepared from Huperzia serrata, a clubmoss that grows on the ground in damp forests and rock crevices. Brewed as an herbal tea, Qian Ceng Ta has been used in China to treat fever, inflammation, and irregular menstruation, and has been used as a diuretic.
In the late 1980’s, researchers in China discovered that a purified alkaloid extracted from Huperzia, Huperzine A, was a potent, reversible inhibitor of acetylcholinesterase (AChE). Huperzine A readily crosses the blood-brain barrier to prevent acetylcholinesterase (AchE) from destroying acetylcholine.
Molecular Monkey Wrench
A study at the Weizmann Institute in Israel uncovered how Huperzine A (Hup-A) works to block acetylcholinesterase.(2) Scientists had previously learned that AchE inhibitors such as tacrine and donepezil worked by sliding into the AChE molecule to "jam up" its molecular machinery and impair its ability to degrade acetylcholine.
By imaging a 3-dimensional structure of the AChE molecule, the researchers were able to peer into the complex folded protein structure to discover a deep chasm, called the active-site gorge. The scientists determined that the active-site gorge acts as a guide to funnel acetylcholine into the interior of the enzyme where it is cut apart prior to recycling.
This study revealed that Huperzine A has a strong specificity for AChE, and is exceptionally well-suited to its new role, fitting into the active sites of acetylcholinesterase much like a key slipping into a lock. "Hup-A appears to bind more tightly and specifically to acetylcholinesterase than the other AChE inhibitors," crystallographer Prof. Joel Sussman, one of the authors of the study said. "It is as if this natural substance was ingeniously designed to fit into the exact spot in AChE where it will do the most good."
Clinical Studies
Hup-A has undergone double blind, placebo-controlled clinical trials in China in patients suffering from various memory disorders, including AD. In fact, it is estimated that in the past few years 100,000 people have been treated in China with Hup-A. Researchers in China claim that it helps normal elderly with memory problems as well as people with AD.
Double-blind, placebo-controlled clinical trials in China have demonstrated that patients suffering from Alzheimer’s and various other memory disorders gain significant benefit, both in terms of memory and life quality. Xu et al. conducted a placebo-controlled, double-blind study in which subjects with AD were given 200 mcg/day Hup-A or placebo for 8 weeks. Statistically significant improvement was achieved in 58% of the treated group with respect to cognitive function and their ability to retrieve past memories.(3)
In one study, Chinese researchers of the Department of Pharmacology, Zhejiang Academy of Medical Sciences, Hangzhou, China, examined the effects of Hup-A on six volunteers. They concluded that Hup-A had a high rate of absorption and distribution in the body, and was without adverse side effects.(4)
A second study conducted by researchers at Zhejiang Medical University, focused on the efficacy of Hup-A on memory, cognition, and behavior in Alzheimer's disease. This multicenter, double-blind, placebo controlled study found that about 58% (29/50) of patients treated with Hup A showed improvements in their memory, cognition, and behavioral functions. No severe side effects were found. All patients were evaluated with Wechsler memory scale, Hasegawa dementia scale, mini-mental state examination scale, activity of daily living scale, treatment emergency symptom scale, and measured with BP, HR, ECG, EEG, ALT, AKP, BUN, Cr, Hb, WBC, and urine routine. Their conclusion was that "Hup-A is a promising drug for symptomatic treatment of Alzheimer's disease."(4)
In a related paper, noted neurologist, Alan A. Mazurek, M.D., reported on the results of an office-based trial studying the safety and efficacy of Hup-A as a treatment for Alzheimer's disease. Mazurek evaluated the safety and efficacy of Hup-A in an open-label trial involving 29 patients with mild to moderate AD.(5)
Twenty-two patients (75.9%) completed the three-month study. Only two patients reported adverse effects, one being an apparently unrelated hemorrhagic infarct that resolved without treatment. No gastrointestinal side effects, nausea, diarrhea, cardiac effects or headache were reported. Status Examinations’ (SMMSE) improvement of one point or greater was seen at one, two and three months. Mazurek reported that improvements appeared to be dose related, with those on the higher dosages exhibiting the greatest improvement. Wrote Mazurek, "Huperzine A appears to be safe, well-tolerated, and effective in the symptomatic treatment of AD."
Other Benefits
In addition to its activity as an AChE inhibitor, ongoing research suggests that Hup-A has a wider role to play in supporting neuroprotective functions. Researchers recently discovered that Hup-A inhibits glutamate-induced cytotoxicity, protecting neonatal hippocampal and cerebellar neuronal cells in culture from death caused by the amino acid glutamate. In addition to protecting from glutamate-induced cytotoxicity, researchers were also surprised to learn that Huperzine A promotes new dendrite outgrowth of neuronal cultures.
Potential Protection for Chemical Warfare
Researchers at the Walter Reed Army Institute of Research in Washington D.C. are conducting studies into Huperzine’s potential role as a pretreatment drug to protect against chemical warfare nerve agent poisoning. In one study, Huperzine A was found to be twice as effective in protecting mice against the lethal effects of the nerve agent soman when compared to physostigmine.6 Huperzine A’s effects lasted for six hours compared to only 90 minutes for physostigmine, providing further evidence for the slow clearance of Huperzine from the body.
Safety
Huperzine A has a wide margin of safety. Toxicology studies show Huperzine A to be non-toxic even when administered at 50-100 times the human therapeutic dose! The extract is active for 6 hours at a dose of 2 µg/kg with no remarkable side effects.
Summary
Huperzine A appears to be a safe memory supplement. Clinical research has shown that Huperzine A is superior to other cholinesterase inhibitors such as tacrine and donepezil. Huperzine A is rapidly absorbed when taken orally, and possesses a very slow rate of dissociation from the enzyme and a longer duration of action. Studies in rodents show that AChE remains inhibited by 33% after 6 hours.
Huperzine A has been shown to be effective in inhibiting the actions of AChE to increase acetylcholine concentrations and alleviate some of the symptoms associated with acetylcholine deficiencies. Significant effects have been noted in patients both in terms of their life quality and their ability to retrieve past memories. These findings suggest that Hup-A is a unique and exciting supplement for supporting memory in the healthy aging human.
References
1. Watkins PB, Zimmerman HJ, Knapp MJ. Hepatotoxic effects of tacrine
administration in patients with Alzheimer's disease. JAMA 1994 Apr 6; 271:992-8
2. Raves ML, Harel M, Pang YP, Silman I, Kozikowski AP, Sussman JL. Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A. Nat Struct Biol 1997 Jan;4(1):57-63.
3. Xu SS; Gao ZX; Weng Z; Du ZM; Xu WA; Yang JS; Zhang ML; Tong ZH; Fang YS;Chai XS; et al, Efficacy of tablet huperzine-A on memory' cognition' and behavior in Alzheimer`s disease. Chung Kuo Yao Li, Hsueh Pao16:391-5, 1995.
4. (Qian BC, Wang M, Zhou ZF, Chen K, Zhou RR, Chen GS. Pharmacokinetics of tablet huperzine A in six volunteers. Chung Kuo Yao Li Hsueh Pao 1995 Sep;16(5):396-8)
5. Mazurek, A. An open label trial of Huperzine A in the treatment of Alzheimer’s disease. Alternative Therapies, March 1999. Vol. 5, No. 2:97.
6. Saxena A, Qian N, Kovach IM, Kozikowski AP, Pang YP, Vellom DC, Radic Z, Quinn D, Taylor P, Doctor BP. Identification of amino acid residues involved in the binding of Huperzine A to cholinesterases. Protein Sci 1994 Oct;3(10):1770-8.
* These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. |
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