Treat Sleep Apnea – Prevent Vascular Dementia

A new study links sleep apnea to strokes and vascular dementia. Early treatment of sleep apnea can protect you from these vascular events.
Study Highlights:

-  Sleep apnea is common in people with silent strokes and small lesions in the brain. This vascular damage often evolves into vascular dementia.
-  Having more than five sleep apnea episodes per night was associated with silent strokes.
-  Early treatment of sleep apnea may help reduce risk of silent strokes in these patients.

People with severe sleep apnea may have an increased risk of silent strokes and small lesions in the brain, which are common foundations of vascular dementia.

The research came out of a small study presented at the American Stroke Association’s International Stroke Conference 2012.

The researchers found:
-  Ninety-one percent (51 of 56) of the patients who had a stroke had sleep apnea and were more likely to have silent strokes and white matter lesions that increased risk of disability at hospital discharge.
-  Having more than five sleep apnea episodes per night was associated with silent strokes.
-  More than one-third of patients with white matter lesions had severe sleep apnea and more than 50 percent of silent stroke patients had sleep apnea.
-  Even though men were more likely to have silent infarcts, correlations between sleep apnea and silent infarcts remained the same after adjustment for such gender differences.

As the strokes, infarcts and lesions accumulate, the vascular damage to the brain increases. If left unchecked, too much damage cascades into vascular dementia.
Jessica Kepplinger, M.D., is the study’s lead researcher and stroke fellow in the Dresden University Stroke Center’s Department of Neurology at the University of Technology in Dresden, Germany. Dr. Kepplinger said,

"We found a surprisingly high frequency of sleep apnea in patients with stroke that underlines its clinical relevance as a stroke risk factor."
"Sleep apnea is widely unrecognized and still neglected. Patients who had severe sleep apnea were more likely to have silent strokes and the severity of sleep apnea increased the risk of being disabled at hospital discharge."

The patients — average 67 years old, white and 54% women — underwent overnight in-hospital testing for sleep apnea.

MRI and CT scans were used to check for silent strokes and white matter lesions. Neuroradiologists were blinded to the sleep study findings and outcome.

Researchers suggested sleep apnea should be treated the same as other vascular risk factors such as high blood pressure.

Kepplinger said, "Demographic characteristics in our study are comparable to western European populations, but our findings may not be entirely generalizable to other populations with diverse ethnicities such as in the U.S."

The researchers plan more studies on sleep apnea, particularly in high-risk patients with silent strokes and white matter lesions, to determine the impact of non-invasive ventilation and on short-term clinical outcome, researchers said.

WATCH VIDEO -> Preventative Tips-Treat Sleep Apnea To Prevent Vascular Dementia

More information on:

1.  Sleep Apnea Ages Your Brain

2.  Is Sleep Apnea Connected to Dementia?

3.  Sleep Related Breathing Disorders


(Source: Alzheimer's Weekly and Dementia Weekly News, 12 February 2012)

Research Update : In Mice, Cancer Drug Reduces Beta-Amyloid and Helps Memory

(Source: Alzheimer's Association Research Update, 10 February 2012)

A report published online by Science Express on Feb. 9, 2012, describes a research study in mouse models of Alzheimer's disease of an FDA-approved cancer therapy called bexarotene. The researchers believe that drug will enhance clearance of an abnormal protein associated with Alzheimer's (beta amyloid protein) from the brain by increasing levels of another protein, known as ApoE. The scientists found that the orally-administered drug rapidly lowered levels of soluble beta amyloid and amyloid plaques in both young and older test animals, and also improved some cognitive and behavioral deficits. This study is exciting because it investigates a possible new approach to treating Alzheimer's disease.

Bexarotene is used to treat cutaneous T-cell lymphoma (CTCL, a type of skin cancer) in people whose disease could not be treated successfully with at least one other medication.

This study, while very interesting, is also very preliminary. Mouse models of Alzheimer's are limited in how closely they represent human Alzheimer's. We are still far away from knowing if this has potential as a therapy for people with Alzheimer's. However, it is intriguing preliminary research that deserves further study.

People with Alzheimer's and their caregivers should not ask their doctor for this drug to treat Alzheimer's disease. That said, investigating an already FDA-reviewed and -approved therapy may mean that the drug development process takes a somewhat shorter time because the drug has already been tested in people. There is still a great deal to learn. For example, without trials in people with Alzheimer's, we know nothing yet about dose levels or how this compound may interact with approved Alzheimer's drugs.

To learn more, following is a report from the Washington Post on 10 February 2012

Cancer Drug Shows Promise In Mouse Alzheimer’s Study

Mice in the early stage of Alzheimer’s disease had some of their brain abnormalities reversed and their declining mental function restored when they were given low doses of a rarely used cancer drug.

The drug, bexarotene, stimulated the removal of ­beta-amyloid, a substance whose accumulation in the brain appears to be the main cause of Alzheimer’s dementia. After treatment, the animals fared better in tests of memory and social behavior, according to a study published online Thursday by the journal Science.

The findings were dramatic, but their relevance to people with Alzheimer’s disease is unknown. But because the drug is already approved for human use, finding out may be easier than if the drug were an entirely new chemical compound.

“It has to work in humans like it works in mice or we can pick up and go home,” said Gary E. Landreth, a neuroscientist at Case Western Reserve University School of Medicine, who headed the experiment.

A study of bexarotene’s effects in normal brains will start in a few months. Clinical trials in people with early Alzheimer’s — or at high risk for the disease for genetic reasons — will take years. If the drug’s effect in human brains turns out to be different, it may never move on to be tested in Alzheimer’s patients.

Nevertheless, the researchers think speed is important, as they fear that people might start using the drug before it is fully evaluated. A few days ago, Landreth got a call from a physician in another city. A person who had heard of the drug through the grapevine had asked for a prescription for bexarotene.

“We’ve got to work fast, and we have got to be right. We can’t screw this up,” Landreth said.

About 5.4 million Americans have Alzheimer’s disease, which is the leading cause of dementia. About 5 percent of people in their late 60s suffer from it, and possibly half of people in their late 80s. By 2050, 1 in 85 people worldwide will have the disease, according to one estimate.

Bexarotene is in the retinoid family of compounds, which are all chemically related to Vitamin A. Retinoids affect cell division and growth, immunity and other essential biological functions.

Sold under the trade name Targretin, bexarotene is approved by the Food and Drug Administration as a treatment for cutaneous T-cell lymphoma, a disease diagnosed in about 3,000 Americans a year. It is an “orphan drug,” a designation that gives drug companies an incentive to develop medicines for rare diseases. Orphan drugs stay under patent protection longer than regular drugs. It has been tried against other forms of cancer, without impressive results.

Numerous “candidate” Alz­heimer’s drugs, which looked promising in lab studies, have washed out in recent years.

Last month, Pfizer and a smaller partner announced that they were abandoning a drug called Dimebon as a possible Alzheimer’s drug after it failed to show benefit in a clinical trial. In 2010, Lilly halted development of a different compound, sem­agacestat. At the Alzheimer’s Association, an advocacy organization, the new study’s results were greeted with that history noted.

“This is an early study and it was in mice,” said Maria C. Carrillo, the organization’s director of scientific relations. “We need to be cautiously optimistic and pursue this lead as we would any other.” She added that what makes “this an exciting study is that it involves a repurposed drug.”

The Case Western experiments were conducted by Paige E. Cramer, a graduate student in Landreth’s lab. The mice used had genetic defects that allowed beta-amyloid to accumulate in their brains, which in turn changed their behavior. The animals, however, are an imperfect model for the human disease. They don’t lose brain cells after beta-amyloid accumulates as people with Alzheimer’s do. (In people, dementia can begin even before cells die, as beta-amyloid disrupts the normal firing of nerve cells.)

Bexarotene spurred the production of “apoE,” a protein that breaks down beta-amyloid molecules floating in the watery fluid between brain cells. Beta-amyloid levels fell by 25 percent within a few days of a single dose. The drug also stimulated housekeeping cells called microglia to consume plaques of solidified beta-amyloid.

While the density of plaques fell by 75 percent over a few weeks, eventually they reaccumulated. Curiously, however, the animals’ behavior didn’t regress to its former state.

“It appears that the measurable activity of the brain is not affected by the presence of the plaques. I think that is a really interesting finding that will stimulate a lot of new science,” Landreth said.

The behavioral tests involved an animal’s ability to remember a cage in which it had gotten a shock, to find a submerged platform in a pool of water, to identify a smell and to build a nest. After treatment with the drug, all those activities returned to normal.

Several physicians with patients taking bexarotene say they’ve never noticed mental improvement from the drug, although they have few, if any, demented patients under their care.

“I have treated over 500 patients with cutaneous T-cell lymphoma in studies and in practice with bexarotene and have not heard any beneficial effect on the brain or cognitive function,” Madeleine Duvic of M.D. Anderson Cancer Center in Houston wrote in an e-mail.

“We really didn’t see anything like this,” said Heather Wakelee, a cancer researcher at Stanford University. She noted, however, that demented people were excluded from studies of bexarotene in advanced cancer.

ALZHEIMER'S ASSOCIATION INVOLVEMENT

Six months before this research was published, the Alzheimer's Association awarded the senior scientist on this article, Gary Landreth of Case Western Reserve University, Cleveland, our prestigious Zenith Award in 2011 for research that will follow on from this study to investigate this drug and how and why it works in this way, perhaps setting the stage for trials in people.

We need to create more treatment targets for Alzheimer's disease and the only way to do that is with more research, especially basic research into the causes and progression of the disease. The Alzheimer's Association commendsthe Obama Administration for dedicating new resources in the fight against Alzheimer's in a uniquely challenging fiscal year in advance of the first ever National Alzheimer's Plan. The Alzheimer's Association will continue to support the process underway to develop the first National Alzheimer's Plan led by Health and Human Services Secretary Kathleen Sebelius. This will help ensure the nation is equipped to overcome Alzheimer's the public health crisis of this century and meet the goal set forth by the Administration to prevent and effectively treat Alzheimer's disease by 2025.

Metals Could Be A Potential Target In Fighting Alazheimer's

One of the many theories explaining Alzheimer's disease is that some of the harm is caused by toxic metals accumulating in brain. Now a new study lends more credibility to the toxic metal theory.

Research into how iron, copper, zinc and other metals work in the brain may help unlock some of the secrets of degenerative diseases like Alzheimer's and Parkinson's.

Iron and copper appear to accumulate beyond normal levels in the brains of people with these diseases, and a new, Australian study published Sunday shows reducing excess iron in the brain can alleviate Alzheimer's-like symptoms - at least in mice.

A genetic mutation related to regulating iron is linked to ALS, or Lou Gehrig's disease. Zinc, on the other hand, appears to impair memory if its levels get too low or if it gets into a brain region where it doesn't belong, as it can with traumatic brain injury.

Research into the complicated, invisible roles these metals play in brain diseases has lagged behind study of the more-visible proteins that are damaged or clump together in the brains of Alzheimer's and Parkinson's sufferers. But better understanding metals' role in the brain could help shed light on a range of medical conditions and might offer a new route for developing treatments, scientists say.

"The field is coming around to the idea of the cause of Alzheimer's being multifactorial," and disturbed metal regulation could be one of those factors, says Ralph Nixon, Chairman of the Alzheimer Association's Medical and Scientific Advisory Council and Director of the Silberstein Alzheimer's Institute at New York University.

Tiny metal ions - charged particles of the elements - serve several essential functions in the body, including facilitating chemical reactions to generate energy and preserving the structure of proteins. Strict checks and balances in a healthy body keep metal levels within a tight range.

But the biological changes that come with disease and aging - as opposed to poisoning from outside sources like food, supplements or metal pans - can knock levels of these metals out of whack in the brain.

Iron, for instance, is a "double-edged sword" because it interacts with oxygen to help the body generate energy, but also can produce free radicals, highly reactive molecules that can cause cell damage, says James Connor, professor and vice chairman of neurosurgery at Penn State University in Hershey.

If the body has too little iron, such as with anemia, the body doesn't generate enough energy to sustain important functions. But an overabundance of iron accumulated in the brain is toxic. Significantly higher accumulations of metal have been observed in the brains of people with Parkinson's and Alzheimer's disease than in healthy people of the same age, says Ashley Bush, a Professor of Pathology at the University of Melbourne.

The new study, conducted by Dr. Bush and colleagues and published in the Journal Nature Medicine, examined the amount of iron in the brains of mice that were bred unable to produce the tau protein, which helps stabilize the structure of neurons. Tau damage is associated with Alzheimer's and Parkinson's.

As the mice aged, they suffered symptoms similar to people with both diseases, including impaired short-term memory, and also exhibited an accumulation of iron in their brains. When the researchers gave them a drug removing excess iron, the symptoms reversed. This means normally functioning tau is necessary for removing iron in the brain, Dr. Bush says. The finding bolsters previous research showing that bringing down iron may be a path to new treatments.

"An accumulation of iron in neurons seems to be a final end-stage event in neurodegeneration, whether it be Alzheimer's or Parkinson's, [or] any [condition] related to tau abnormalities," says Dr. Bush, who is also a fellow at the university's Mental Health Research Institute.

Other proteins affected in Alzheimer's also play a role in metal regulation. The amyloid precursor protein is important in helping export iron from the brain, according to work published in the Journal Cell in 2010. Presenilin, another protein that aids in metal uptake, is also disturbed in diseased brains, according to a study published in Journal of Biological Chemistry last year.

Similar findings link copper accumulation and brain disease, though not as much research has been conducted as with iron, scientists say.

In addition to iron accrual, lower-than-normal levels of zinc have been found in patients with Alzheimer's and Parkinson's disease, according to work by George Brewer, an emeritus professor at the University of Michigan, and Edward Fitzgerald at the University at Albany-SUNY, published last year in the American Journal of Alzheimer's Disease and Other Dementias. Dr. Brewer now is a consultant to Adeona Pharmaceuticals Inc., based in Ann Arbor, Mich., which is developing a zinc-based treatment for Alzheimer's, he says.

Besides Adeona, a handful of other biotechnology companies have also been testing experimental metal-lowering drugs for treatment of Alzheimer's or Parkinson's. But developing such drugs is tricky because it is hard to target metals in specific parts of the brain. Simply lowering or increasing the amount overall in the body may not be beneficial, researchers say.

Metals may play a vital role in other brain conditions.

Stephen Lippard, a Chemistry Professor at the Massachusetts Institute of Technology, and colleagues from Duke University and the University of Toronto, found zinc helps neurons communicate in the hippocampus, a brain region involved in learning and memory. Disturbing this interaction, or ushering zinc into a brain region where it doesn't belong, could affect memory formation and the occurrence of epileptic seizures, says Dr. Lippard, who studies the role of metal ions in biology, neuroscience, and medicine. Their work was published in September in Neuron.

"It's important that the medical community continue to be alerted to the connection between metal ions and neurological disease," says Dr. Lippard.

Dr. Connor and his Penn State team have shown that patients with ALS have a higher rate of mutation in a gene, HFE, that regulates iron absorption. Carriers of the mutation have higher levels of iron in the brain and a fourfold increase in risk of ALS, according to a 2004 study published in the Journal of Neurological Sciences.

They have also been trying to figure out why the patients with multiple sclerosis lose the protective coating, called myelin, surrounding their axons, the part of the nerve cell that conducts electrical impulses. The cells responsible for making the myelin have elevated iron, making them more vulnerable to damage and death, says Dr. Connor.

Metals, Positive and Negative

Several metals play vital roles in the human body, but diseases can disturb their balance, causing harm.

Iron

Normal function: Involved in oxygen transport; needed to make energy for cells.

In the brain: Excess levels of iron are linked to Alzheimer's and Parkinson's diseases. Proteins and mutations related to iron delivery or absorption appear to be connected to Lou Gehrig's disease and multiple sclerosis.

Copper

Normal function: Helps transport oxygen, often works in tandem with iron.

In the brain: Wilson disease stops the body from getting rid of copper, which can cause speech problems, tremors and muscle stiffness. Disruption in copper regulation causes Menkes disease, which leads to abnormally low copper levels.

Zinc

Normal function: Helps make DNA and RNA, regulates cell death, and plays a role in short-term memory and learning.

In the brain: Low levels or the presence of the metal in areas of the brain where it isn't normally found are thought to impair memory.

Watch Video ->  Do Toxic Metals In The Brain Cause Alzheimer's 

(Source: WSJ (The Wall Street Journal), 31 January 2012, By SHIRLEY S. WANG) 

(SAT) 11FEB12 Talk "Caring with Love" Organized By ADFM KL-PJ Caregivers Support Group

Dear Caregivers/Members,

ADFM KL-PJ ALZHEIMER'S CAREGIVERS SUPPORT GROUP

MONTHLY GATHERING  & TALK

“CARING WITH LOVE”       

   

SATURDAY, 11 FEBRUARY 2012 AT 2:00PM

ADFM PJ DAYCARE CEMTRE

(No. 6, Lorong 11/8E,Section 11, 46000 PJ)

BY SPEAKER, MADAM LEONG SIK WAI

Program:
2:00pm  :  Registration of Attendance
2:30pm  :  Welcome address by the Chairperson
2:40pm  :  “Caring with Love” by Guest Speaker, Mdm Leong Sik Wai,
3:40pm  :  Sharing and Q & A Session
4:20pm  :  Refreshments

The Objective:

·         To reinforce on the patient’s feeling and caregiver’s coping skill.

·         How caregivers can better understand the physical, emotional, and mental changes of their patients.

·         Caregiver’s feeling - understand own feeling, be able to cope with patient’s condition/changes.

·         Learn the techniques - “LOVE” (how to love ), Emotion Freedom Technique.

The Speaker:

Mdm Leong Sik Wai is currently a Nutrionist with Merck, a Pharmaceutical Company, a Caregiver for her late Dad, Speaker for the Malaysian Healthy Aging Society’s Caregivers Workshop on “Caring with Love” and Volunteer with the Tzu Chi Charity Foundation. She obtained her BSc.(Hons) Nutrition from UKM.  

To Register, submit "Registration Form" and Email: jenny@adfm.org.my OR Fax: 03 - 7960 8482.

Further enquiries, call Jenny at ADFM 03-7956 2008/7958 3008 / SMS 016-608 2513 or Email: jenny@adfm.org.my

JOIN ADFM NATIONAL ALZHEIMER'S CAREGIVERS NETWORK

 The National Platform for The Caregivers Community

SIGN UP at: http://admalaysia.ning.com/main/authorization/signUp

From:  ADFM KL-PJ Caregivers Support Group

January 2012

Advice to Keep Dementia at Bay

Recently, researchers looking into cognitive decline and dementia have made encouraging findings. Although it was believed that the adult brain could not develop new neurons (or brain cells), scientists have learned in the past decade or so that the human brain is pliable and adaptive. The brain can actually add new neurons even late in life and continually form new connections among existing neurons -- a phenomenon known as neuroplasticity.

This means that while an aging brain may have signs of damage, it can often compensate for them, at least initially. And engaging in mentally stimulating activities like reading, taking a class or playing board games is one way to bolster this process.

This compensation process depends on your "cognitive reserve," the extra, perhaps unused, amount of cognitive ability that can make up for the loss of brain functioning when your brain shows signs of dementia due to the death of cells and their replacement by beta-amyloid plaques. Genetics, early childhood stimulation and education level can influence cognitive reserve but are essentially immutable once you're an adult.

Fortunately, studies have found that you can also increase your cognitive reserve and delay the onset of dementia through a variety of intellectually stimulating leisure activities in middle and later life.

A study in the journal Neurology, for example, found that among 101 people who eventually developed dementia, those who frequently participated in one or more activities, such as reading, writing, doing crossword puzzles, playing card or board games, having group discussions or playing music experienced memory decline more than one year later than those who participated in these activities less often. These pursuits built cognitive reserve and delayed dementia as much as a higher education level did.

It's worth noting that researchers have discovered that watching television is a passive activity that doesn't really stimulate the mind at all; on the contrary, watching television is associated with an increased risk of cognitive decline. One study found that TV watchers were 10 percent more likely than nonwatchers to experience cognitive impairments over a five-year period. A possible explanation: Time spent in front of the TV means less time for the mental, social and physical activities that can help delay dementia.

(Source:  John Hopkins Health Alert, 9 January 2012)

Medical News / Treatment Articles: Drugs In Dementia - Everything You Wanted to Know

VIDEO - Watch Dr Frank Molnar's brilliant presentation on "Drugs in Dementia - The Good, The Bad, The Ugly" at the October 2011 Alzheimer Society of Ottawa and Renfrew County education seminar. Learn the best use of Namenda, Antipsychotics and Cholinsterase Inhibitors like Aricept. See what distinguishes Alzheimer's, Frontotemporal Lobar, Lewy body, Parkinson's, PPA, Semantic and Vascular Dementias. Understand the side-effects and interactions of antibiotic, antidepressant, heart, narcotic and other medications in dementia. Whether patient, caregiver or neurologist, you'll get many answers.

Recommend to read:

1. Charts Comparing Medications to Treat Alzheimer's Disease and Related Dementias

This brief summary does not include all information important for patient use and should not be used as a substitute for professional medical advice. Consult the prescribing doctor and read the package insert before using these or any other medications or supplements. Drugs are listed in alphabetical order.

TECHNICAL FACTS

BRAND NAME	GENERIC (Int'l) NAME	STAGE OF ILLNESS	DRUG TYPE	HOW IT WORKS	LOGO
ARICEPT®	donepezil	Mild to moderate & Moderate to severe	Cholinesterase inhibitor	Prevents the breakdown of acetylcholine in the brain.
EXELON®	rivastigmine	Mild to moderate	Cholinesterase inhibitor	Prevents the breakdown of acetylcholine and butyrylcholine (a brain chemical similar to acetylcholine) in the brain.
NAMENDA®	memantine	Moderate to severe	N-methyl D-aspartate (NMDA) antagonist	Blocks the toxic effects associated with excess glutamate and regulates glutamate activation.
RAZADYNE®	galantamine	Mild to moderate	Cholinesterase inhibitor	Prevents the breakdown of acetylcholine and stimulates nicotinic receptors to release more acetylcholine in the brain.

PRESCRIPTION FACTS

BRAND NAME	MANUFACTURER’S RECOMMENDED DOSAGE	GENERIC VERSION?	FORMAT	COMMON SIDE EFFECTS	MORE INFORMATION
ARICEPT®	.  Initial dose: 5-mg tablet once a day .  May increase dose to 10 mg/day after 4-6 weeks if well tolerated.	No	Tablet	Nausea, vomiting, diarrhea	Visit www.fda.gov/cder. Click on “Drugs@FDA,” search for ARICEPT®, and click on drug-name links to see “Label Information.
EXELON®	.  Capsule: Initial dose of 3 mg/day (1.5 mg twice a day). .  May increase dose to 6 mg/day (3 mg twice a day), 9 mg (4.5 mg twice a day), and 12 mg/day (6 mg twice a day) at minimum 2-week intervals if well tolerated. .  Patch: Initial dose of 4.6 mg once a day; may increase to 9.5 mg once a day after minimum of 4 weeks if well tolerated. .  Also available as oral solution; same dosage as capsule.	No	Capsule Patch Oral Solution	Nausea, vomiting, diarrhea, weight loss, loss of appetite, muscle weakness	Visit www.fda.gov/cder. Click on “Drugs@FDA,” search for EXELON®, and click on drug-name links to see “Label Information.”
NAMENDA®	.  Initial dose: 5-mg tablet once a day. .  May increase dose to 10 mg/day (5 mg twice a day), 15 mg/day (5 mg and 10 mg as separate doses), and 20 mg/day (10 mg twice a day) at minimum 1-week intervals if well tolerated. .  Also available as oral solution; same dosage as above.	No	Tablet Oral Solution	Dizziness, headache, constipation, confusion	Visit www.namenda.com. Click on “Prescribing Information” to see the drug label.
RAZADYNE®	. Tablet: Initial dose of 8 mg/day (4 mg twice a day). .  May increase dose to 16 mg/day (8 mg twice a day) and 24 mg/day (12 mg twice a day) at minimum 4-week intervals if well tolerated. .  Extended-release capsule: Same dosage as above but taken once a day. .  Also available as oral solution; same dosage as above.	Yes	Tablet Once-A-Day Extended Release Capsule Oral Solution	Nausea, vomiting, diarrhea, weight loss, loss of appetite	Visit www.razadyneer.com. Click on “Important Safety Information” to see links to prescribing information.

2.  Introduction To Medications

Learn about the 4 prescription drugs  currently approved by the U.S. Food and Drug Administration (FDA) to treat people who have been diagnosed with Alzheimer’s disease (AD). Treating the symptoms of AD can provide patients with comfort, dignity, and independence for a longer period of time and can encourage and assist their caregivers as well.

It is important to understand that none of these medications stops the disease itself.

Treatment for Mild to Moderate AD

Medications called cholinesterase inhibitors are prescribed for mild to moderate AD. These drugs may help delay or prevent symptoms from becoming worse for a limited time and may help control some behavioral symptoms. The medications include: Razadyne® (galantamine, formerly known as Reminyl® and now available as a generic drug), Exelon® (rivastigmine), and Aricept® (donepezil). Another drug, Cognex® (tacrine), was the first approved cholinesterase inhibitor but is rarely prescribed today due to safety concerns.

Scientists do not yet fully understand how cholinesterase inhibitors work to treat AD, but research indicates that they prevent the breakdown of acetylcholine, a brain chemical believed to be important for memory and thinking. As AD progresses, the brain produces less and less acetylcholine; therefore, cholinesterase inhibitors may eventually lose their effect.

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No published study directly compares these drugs. Because they work in a similar way, switching from one of these drugs to another probably will not produce significantly different results. However, an AD patient may respond better to one drug than another.

Treatment for Moderate to Severe AD

A medication known as Namenda® (memantine), an N-methyl D-aspartate (NMDA) antagonist, is prescribed to treat moderate to severe AD. This drug’s main effect is to delay progression of some of the symptoms of moderate to severe AD. It may allow patients to maintain certain daily functions a little longer than they would without the medication. For example, Namenda® may help a patient in the later stages of AD maintain his or her ability to use the bathroom independently for several more months, a benefit for both patients and caregivers.

Namenda® is believed to work by regulating glutamate, an important brain chemical. When produced in excessive amounts, glutamate may lead to brain cell death. Because NMDA antagonists work very differently from cholinesterase inhibitors, the two types of drugs can be prescribed in combination.

The FDA has also approved Aricept® for the treatment of moderate to severe AD.

Dosage and Side Effects

Doctors usually start patients at low drug doses and gradually increase the dosage based on how well a patient tolerates the drug. There is some evidence that certain patients may benefit from higher doses of the cholinesterase inhibitors. However, the higher the dose, the more likely are side effects. The recommended effective dosages of drugs prescribed to treat the symptoms of AD and the drugs’ possible side effects are summarized in the table (see below).

Patients should be monitored when a drug is started. Report any unusual symptoms to the prescribing doctor right away. It is important to follow the doctor’s instructions when taking any medication, including vitamins and herbal supplements. Also, let the doctor know before adding or changing any medications.

3.  How Do Alzheimer's Medications Differ?  

Which Alzheimer's medications are best? To help answer this question, the ACP/AAFP Committee issued guidelines on the five available medications for Alzheimer's.

An American College of Physicians (ACP) and American Academy of Family Physicians (AAFP) committee issued a clarifying guideline on drug treatment of dementia. Their advice? When trying to decide which medicine is best for a person, the most important considerations are:

    Side effects

    Ease of Use

    Cost

There's no proof that any one of the five drugs available in the United States to treat dementia in general, and Alzheimer's in particular, is more effective than the others.

The committee reviewed published studies for outcomes such as cognition, global function, behavior/mood, and quality of life/activities of daily living. They found only limited high-quality scientific evidence of the effectiveness of the drugs and therefore developed the following cautious recommendations:

·  The decision to use approved drugs for dementia should be based on an individualized patient assessment.

·   The choice of drugs should be based on tolerability, adverse effect profile,ease of use, and cost.

·     There's an urgent need for more clinical research to improve knowledge about the clinical effectiveness of drugs used to treat dementia.

The committee recommended the following kinds of research:

·         Evaluate the effectiveness of drug therapy for dementia and assess whether treatments affect key outcomes, such as institutionalization.

·         Evaluate the appropriate duration of therapy.

·         Head-to-head testing of drugs.

·         Test drugs in combination therapy.

The guideline was published in the Annals of Internal Medicine.

Currently, there are five FDA-approved drugs for treatment of dementia. These include four acetylcholinesterase inhibitors - donepezil (Aricept®), galantamine (Razadyne®, Reminyl), rivastigmine (Exelon®), and tacrine - and one neuropeptide-modifying agent - memantine (Namenda®).

While these drugs may improve symptoms or slow disease progression, they don't cure dementia or repair brain damage.

"Doctors, patients and family caregivers desperately want information on how to treat this disease," Dr. Amir Qaseem, senior medical associate in the ACP's Clinical Programs and Quality of Care Department, said in a prepared statement.

"More research is warranted, because the available evidence concerning these pharmaceuticals' effects on quality of life is mixed, and the clinical significance of many of the findings is questionable," Dr. Kenneth G. Schellhase, an AAFP representative on the committee, said in a prepared statement. "In addition, the duration of existing trials was usually less than one year, providing insufficient information to determine the optimal length of treatment, and few trials compare one drug directly with another."

Most existing studies of the five approved dementia drugs focused on statistical significance of changes, but clinically important improvement is what matters to patients, caregivers and doctors, the committee noted. Many studies measuring clinical improvements are currently in progress throughout the world.

4.  Behavioral Benefits of Alzheimer's Medications

People with Alzheimer's and other dementias often take medications called cholinesterase inhibitors.

Medical research has demonstrated they are also a safe alternative to antipsychotics for the behavioral and psychological symptoms of dementia.

This is according to a study that appears in the December 2008 edition of Clinical Interventions in Aging.

Currently, the main cholinesterase inhibitors that are offered for Alzheimer's and other dementias are:

Brand Name	Generic Name
Aricept	donepezil HCL
Exelon	rivastigmine
Razadyne®	galantamine HBr

Investigators from the Indiana University School of Medicine, the Regenstrief Institute and Wishard Health Services reviewed nine randomized, double-blind, placebo-controlled clinical trials evaluating the effectiveness of three popular cholinesterase inhibitors in managing behavioral and psychological symptoms displayed by patients with Alzheimer's disease.

The researchers report that the trial results indicate cholinesterase inhibitors led to a statistically significant reduction in behavioral and psychological symptoms such as aggression, wandering or paranoia when using the same dosage as administered for improving cognitive impairment.

Nine out of 10 Alzheimer's disease patients display behavioral and psychological symptoms of their disease. The review of the clinical trials revealed that cholinesterase inhibitors are safe, producing no major side effects.

"There is a need for safe alternatives to the anti-psychotic drugs currently used to manage the behavioral and psychological symptoms of Alzheimer's disease. The results of the studies we analyzed are encouraging and suggestive that cholinesterase inhibitors are safe and effective alternatives. However, they are underutilized and typically prescribed for less than three months and for less than 10 percent of patients with Alzheimer's disease. Our findings might provide clinicians with useful data to justify the appropriate use of these medications," said Malaz Boustani, M.D., corresponding author of the Clinical Interventions in Aging paper. Dr. Boustani is assistant professor of medicine at the IU School of Medicine, a Regenstrief Institute research scientist, a research investigator with the IU Center for Aging Research, and chief research officer of the Indianapolis Discovery Network for Dementia.

In Alzheimer's disease there is a decrease in acetylcholine, a chemical in the brain that assists memory, thought and judgment. Cholinesterase inhibitors raise acetylcholine levels. Increased concentrations of acetylcholine in the brain leads to increased communication between nerve cells and may improve or stabilize the symptoms of Alzheimer's disease in the early and moderate stages of progression.

Noll Campbell, PharmD, a clinical pharmacy specialist in geriatric psychiatry with Wishard Health Services and corresponding author of the paper, said that, "This class of medications has already been approved by the Food and Drug Administration to manage symptoms of Alzheimer's-type dementia, although their potential benefits on behavioral symptoms are not frequently identified by many prescribers. Clinical trials of cholinesterase inhibitors have shown benefits in several domains of cognitive function as well as behavioral symptoms associated with dementia, and may improve the management of behavioral problems while reducing the use of more harmful medications that are needed to control behaviors."

Dr. Boustani noted that the vast majority of busy primary care physicians, the doctors who see the majority of patients with Alzheimer's disease, are unaware of the details of the studies analyzed in the Clinical Interventions in Aging paper and he hopes that this new paper, which reviewed the studies, will encourage them to prescribe cholinesterase inhibitors, with its benefits for both cognition and behavior symptoms to their Alzheimer's disease patients. 

5.  Moderate Your Medications

Almost 190,000 Australians have dementia and as Australia's population ages, dementia becomes a bigger challenge for doctors, their patients and carers.

According to the National Prescribing Service Limited (NPS), there are limited benefits to using cholinesterase inhibitors and memantine in the treatment of patients with dementia drug therapy.

Research indicates that the benefits of cholinesterase inhibitors and memantine are small, some people will not respond and adverse effects are common, says NPS clinical expert, Education and Quality Assurance Program Manager, Ms Judith Mackson.

Because the response rate is low and the effects of cholinesterase inhibitors and memantine are small, if these medicines are to be used, it is imperative that they are monitored in order to objectively assess their effectiveness for the patient.

Antipsychotics have a very limited role in some of the challenging behaviours of dementia and the risk of cerebrovascular events and all-cause mortality increases. Consequentially if there are no clear beneficial effects, a trial withdrawal should be attempted because for many patients symptoms will NOT worsen on withdrawal.

A planned, regular and also opportunistic approach to reviewing medications is recommended not only for people with Alzheimer's disease, but all older people using medicines, Ms. Mackson said.

She says health professionals need to encourage the use of non-pharmacological strategies at all stages of dementia. We know that non-pharmacological strategies can help promote and maintain independence, cognitive function and manage the behavioural and psychological symptoms of dementia.

Carers may see medication as the only option, so they will need support and information to help manage their expectations on the effectiveness of medication, she said. "Appropriate counseling for carers from health professionals on the limited benefits of drug therapy is key to best practice. In addition, carers may need information about the process of withdrawal if there are no clear beneficial effects of the medication."

To learn more about how to make informed decisions when working with patients with dementia, the new NPS education program, Treating the symptoms of dementia may be of interest. To obtain a copy,or to find out about the education program, visit the NPS website www.nps.org.au.

(Source: Alzheimer's & Dementia Weekly, 2 January 2012)