Thursday, 3 May 2012

Understanding of the Tau Mechanism in Alzheimer's Disease Progression

Mount Sinai scientists have determined how a pathological brain protein called tau contributes to the progression of Alzheimer's disease.

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Researchers at Mount Sinai School of Medicine have gained insight into the mechanism by which a pathological brain protein called tau contributes to the progression of Alzheimer's disease (AD) and other neurodegenerative disorders.

This finding, published in the most recent issue of the Journal of Biological Chemistry, may provide the basis for future investigations on how to prevent tau from damaging brain circuits involved in cognitive function.

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Researchers Gain Better Understanding of the Mechanism Behind Alzheimer's Disease Progression

Giulio Maria Pasinetti
Previous studies have shown that the abnormal folding, or misfolding, and buildup of tau are key neuropathological features of many neurodegenerative disorders, including AD. Some research has demonstrated that AD-type tau neuropathology spreads in the brain, seemingly moving from one brain cell to another.

A research group led by Giulio Maria Pasinetti, MD, PhD, Saunders Family Chair in Neurology at Mount Sinai School of Medicine, explored whether misfolded tau released by neurons from the human brain – also known as paired helical filaments (PHFs) – could actually be taken up by surrounding cells and promote the spread of tau neuropathology. The evidence was gathered by treating human neuronal cell lines with human Alzheimer's disease-derived PHFs. The researchers found that not only did the cells in fact internalize the human PHFs, the abnormal tau then propagated its abnormal state to the native, normal tau protein in the cells.
"While these findings are potentially important for possibly opening new therapeutic avenues in Alzheimer's disease, they also shed light on a new therapeutic target for a wide variety of disorders sharing pathological features with Alzheimer's disease, for which there are currently no cures," said Dr. Pasinetti. "Such diseases include Progressive Supranuclear Palsy, frontotemporal dementia, and other devastating neurodegenerative disorders in which misfolded tau forms aggregates in the brain."
Next the researchers treated the same cell lines with a grape-seed extract enriched in polyphenols, which are natural compounds found in grapes, fruits, and vegetables, based on 2011 research showing the efficacy of this extract in preventing the progression of AD in mice. Dr. Pasinetti's group found that a subfraction of this natural grape-seed extract enriched in polyphenols was able to prevent the cell-to-cell spread of tau pathology in the same human neuronal cell lines.
"Pathology in neurodegenerative disorders is thought to be initiated decades before disease onset," said Dr. Pasinetti. "While further research is needed in humans, we hypothesize that this grape-derived compound may be a promising therapy for not only treating but preventing neurodegenerative disorders involving tau neuropathology."
Dr. Pasinetti and Jun Wang, PhD, Assistant Professor of Neurology at Mount Sinai, are named inventors of a pending application filed by Mount Sinai School of Medicine titled "Methods Preventing Neurodegenerative Disease" related to the use of grape-seed extracts for the treatment of neurodegenerative diseases and may benefit financially from this patent.

About The Mount Sinai Medical Center

The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of the leading medical schools in the United States.

For more information, visit http://www.mountsinai.org.



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Can Omega-3 and Nutrients Prevent or Delay Alzheimer's Disease

Ingesting one gram of omega-3 per day (equal to approximately half a fillet of salmon per week), is associated with 20 to 30 percent lower blood beta-amyloid levels.

By Bob DeMarco
Alzheimer's Reading Room

My name is Bob DeMarco. I am not a doctor or a scientist. I am an Alzheimer's caregiver. Which I guess makes me some guy with an opinion.

Can what you eat, how much you exercise, how much you use a computer, how you use your brain (puzzles, etc.) effect the odds on whether or not you suffer from Alzheimer's? I think so.

If you read the studies published on this website, you'll learn that you can lower the odds of suffering from dementia. Now this might sound harsh, but if you do the right things you might die before you are diagnosed with dementia.

Lets take my mother, Dotty, as an example. If Dotty had died before the age of 87 years old neither of us would be here. We would never have known that Dotty would become deeply forgetful. Dotty is 95 years old.


Dotty did have something going against her in this scenario -- genetics. The women on Dotty's side of the family live a long long time. All of them. They don't suffer from heart disease, and they don't get serious illnesses. They live on. I guess you could conclude that Dotty lived too long. I don't think so. Frankly, while it is trying, difficult, sometimes burdensome, and even downright scary, we are doing fine.

Together, Dotty and I figured out how to stare Alzheimer's right in the face and tell it to go to hell. I might add we proved two things. We survived and Alzheimer's is not an automatic death sentence. We are not the only One's by the way.

Nikolaos Scarmeas
When you read the results of the study presented below here is what you will find.

People who had higher levels of 10 nutrients in their system: saturated fatty acids, omega-3 and omega-6 polyunsaturated fatty acids, mono-unsaturated fatty acid, vitamin E, vitamin C, beta-carotene, vitamin B12, folate and vitamin D had lower levels of beta-amyloid in their blood.

"Ingesting one gram of omega-3 per day (equal to approximately half a fillet of salmon per week), is associated with 20 to 30 percent lower blood beta-amyloid levels".

Last night Dotty and I ate salmon and brocolli for dinner. Dig.

If you eat a Mediterranean diet and get out in the sun, bright light,  for 15 minutes or so a day, walla, you did it. You did the right thing. You changed the odds of suffering from Alzheimer's.

Yesterday we published an article, Computer Use and Exercise May Reduce the Odds of Memory Loss, that showed study participants who did not exercise and did not use a computer, 20.1 percent were cognitively normal and 37.6 percent showed signs of mild cognitive impairment. Of the participants who both exercise and use a computer, 36 percent were cognitively normal and 18.3 percent showed signs of MCI.

Wouldn't you rather be in the 37.6 percent. By they way, this study did not indicate that if you use a computer and exercise you won't get Alzheimer's. It indicated you might be able to change the odds of suffering from dementia.

None of these studies operate in a vacuum. You have a genetic make up and you do all kinds of things during your life. For example, a small study showed that men who played football in the National Football League (NFL) were about 6 times more likely to suffer from dementia at a young age.

What about men that play high school football, college football or rugby? Are they increasing their own odds of suffering from dementia or CTE? Early studies might be showing they are.

Let's take a man like Bob Blackwell (Carol's husband) was he genetically predisposed to Alzheimer's by birth? I'll let Carol answer that question.

My point here is simple and straightfoward, it seems to me that you want to consider how you might change the odds of suffering from dementia. Who knows, you push it back five years you might die first. You might push it back far enough that it never happened.

Of course, you might end up living longer. What a conundrum, huh?

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Omega-3s Linked to Lower Amyloid Levels

People who had a lot of omega-3 fatty acids in their diets tended to have lower plasma levels of beta-amyloid proteins, possibly reducing their risk of Alzheimer's disease, researchers said.

In a cross-sectional study of more than 1,200 cognitively normal individuals older than 65, omega-3 fatty acid intake was significantly predictive of plasma levels of the 40- and 42-residue forms of beta-amyloid protein (AB40 and AB42, respectively), according to Nikolaos Scarmeas, MD, of Columbia University in New York City, and colleagues.

Adjusting for age, education level, and other factors pushed the relationship between AB40 and omega-3 intake into a strong but nonsignificant trend (beta statistic -10.13, P=0.13). But the association with AB42 remained significant, Scarmeas and colleagues reported online in Neurology (beta statistic -7.70, P=0.02).

The same group had previously published results indicating that a Mediterranean-type diet was associated with lower risk of cognitive impairment and Alzheimer's disease.

Because one of the hallmarks of Alzheimer's disease is beta-amyloid plaque deposits in the brain, Scarmeas and colleagues sought to determine if dietary factors were related to blood levels of AB40 and AB42.

Their study population was drawn from participants in the Washington Heights/Hamilton Heights Columbia Aging Project in New York City, first recruited in 1992 with a second group enrolled in 1999.

As part of this study, participants completed a detailed diet questionnaire and also provided blood samples. The latter were drawn a mean of 1.2 years after collection of dietary information.

The researchers excluded participants already showing dementia when the dietary questionnaire was administered, since their mental status could affect their self-reporting on diet.

A total of 1,219 participants out of the original 2,778 were included in the current analysis. In addition to 345 with prevalent dementia, another 1,025 could not be included because beta-amyloid levels in plasma weren't measured.

In addition to omega-3 intake, Scarmeas and colleagues also estimated intake of nine other nutrients: folate, beta-carotene, monounsaturated fats, saturated fats, omega-6 fatty acids, and vitamins C, D, E, and B12.

Only omega-3 intake was significantly associated with plasma AB40 or AB42 levels in any analysis.

The raw data suggested a powerful link:

AB40: beta -24.74, P<0.001

AB42: beta -12.31, P<0.001

But analysis of participant characteristics revealed a number of covariates. Adjusting for age, race-ethnicity, education level, APOE genotype, total caloric intake, and recruitment wave attenuated the relationships noticeably.

The beta value for AB40 shrank to -11.96 and the P value increased to 0.06. 

The beta value for AB42 also declined, to -7.31, but it remained significant at P=0.02.

Adding adjustments for alcohol drinking and use of certain drugs and nutritional supplements changed the strength of the associations only slightly.

 The researchers' conclusion: "The potential beneficial effects of omega-3 [fatty acid] intake on Alzheimer's disease and cognitive function in the literature might be at least partly explained by an AB-related mechanism," they wrote.

Scarmeas and colleagues noted several limitations to the study, including its cross-sectional design and its reliance on a single measurement of plasma AB40 and AB42 levels, which they characterized as "a moving target" during development of cognitive decline.

Also, the researchers relied on participants' self-reports on diet and examined only 10 of many nutrients contained in food.

Finally, Scarmeas and colleagues acknowledged that plasma beta-amyloid proteins do not necessarily reflect amyloid protein levels in the brain.

Nutrient intake and plasma β-amyloid



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Wednesday, 2 May 2012

Alzheimer's Drug Memantine Fails to Reduce Significant Agitation, Does Help with Behavior and Psychological Symptoms

I read the study presented below with great interest. It is my personal belief that we turned the behavior corner when Dotty was started on the combination of Aricept and Namenda (memantine).

By Bob DeMarco
Alzheimer's Reading Room

Malaz Boustani

If you read the report below you will notice the findings state that memantine "does not ease clinically significant agitation in patients".

The researchers did report signficant improvement in cognitive function and for overall neuropsychiatric symptoms for the group given memantine, but no statistically significant difference in terms of the severe agitation that was the primary focus of the study. The key words here are "severe agitation".

I would say that Dotty was less moody, did improve in cognitive function, and was easier to work with once on memantine (brand name Namenda in the U.S.).

The study indicates that memantine does, can, have real benefits for patients in later stages of Alzheimer's disease.

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Alzheimer's drug fails to reduce significant agitation

A drug prescribed for Alzheimer’s disease does not ease clinically significant agitation in patients, according to a new study conducted by researchers from the U.K., U.S. and Norway. This is the first randomized controlled trial designed to assess the effectiveness of the drug (generic name memantine) for significant agitation in Alzheimer’s patients.

Previous studies suggested memantine could help reduce agitation and improve cognitive functions such as memory. Led by the University of East Anglia in the U.K., the new research found that while memantine does improve cognitive functioning and neuropsychiatric symptoms such as delusion, mood and anxiety, it is no more effective in reducing significant agitation than a placebo.

“Memantine is quite commonly prescribed for Alzheimer’s disease in the U.S. Despite the negative findings regarding agitation, this trial opens a door of hope,” said Regenstrief Institute investigator Malaz Boustani, M.D., MPH, associate professor of medicine at the Indiana University School of Medicine and associate director of the IU Center for Aging Research. “Memantine does appear to help with other behavioral and psychological symptoms of Alzheimer’s disease.”

Dr. Boustani, a co-author of the study, is also the medical and research director of the Healthy Aging Brain Center at Wishard Health Services.

“Efficacy of memantine for agitation in Alzheimer's dementia: a randomized double-blind placebo controlled trial” published in PLoS ONE on May 2. Authors of the study are from Indiana University; the University of East Anglia, University College London, University of Kent, Aston University, Oxleas National Health Service Foundation Trust and Kings College London, all in the U.K.; and the University of Stavanger in Norway.

An estimated 5.4 million Americans have Alzheimer’s disease according to the Alzheimer’s Association. Many are agitated. They may, for example, pace continually, become physically or verbally aggressive or scream persistently. In addition to harming quality of life for the patient, agitation places enormous strain on relationships with family members and care providers, and often results in institutionalization.

“People who have mild symptoms [of agitation] often respond to changes in the environment or psychological treatment, but these methods are impractical in severe agitation," said Chris Fox, M.D., of Norwich Medical School at University of East Anglia, who led the research. "Our findings regarding memantine are disappointing with respect to severe agitation -- particularly as the alternative antipsychotic medications can have significant side effects such as increased rates of stroke and death. However, we hope our study will highlight the urgent need for investment in safe and effective new treatments for this growing disease.”

The team of researchers studied 153 nursing home residents and hospital inpatients with severe Alzheimer’s from September 2007 to May 2010. All the study participants displayed significant agitation requiring clinical treatment. Half were given memantine, and half received a placebo. The researchers reported signficant improvement in cognitive function and for overall neuropsychiatric symptoms for the group given memantine, but no statistically significant difference in terms of the severe agitation that was the primary focus of the study.

Memantine is approved by the U.S. Food and Drug Administration for Alzheimer’s disease. The trial was sponsored by East Kent Hospitals University National Health Service Foundation Trust in the U.K. The study was funded by Lundbeck, a manufacturer of memantine.

“This research suggests that even though memantine can have real benefits for people in the later stages of Alzheimer’s, it may not have all the answers," said Anne Corbett, research manager at the Alzheimer’s Society of the U.K., which was not involved in the research. "However, prescribers should not see the only alternative as being to hand out antipsychotics. These overprescribed drugs double the risk of death and treble the risk of stroke and should always be a last resort for people with dementia.”

"Efficacy of memantine for agitation in Alzheimer's dementia: a randomized double-blind placebo controlled trial" by C. Fox (UEA), M. Crugel (Oxleas NHS Foundation Trust), S. Coulton (University of Kent), I. Maidment (Aston University), B.H. Auestad (University of Stavanger, Norway), A. Treloar (Oxleas NHS Foundation Trust), C. Ballard (Kings College London), M. Boustani (Indiana University and the Regenstrief Institute, USA), C. Katona (University College London) and G. Livingston (University College London) is available online at http://dx.plos.org/10.1371/journal.pone.003



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Computer Use and Exercise May Reduce the Odds of Memory Loss, Mayo Clinic

The study examined exercise, computer use and the relationship to neurological risks such as mild cognitive impairment.

Alzheimer's Reading Room

Combining mentally stimulating activities, such as using a computer, with moderate exercise decreases your odds of having memory loss more than computer use or exercise alone, a Mayo Clinic study shows.

Previous studies have shown that exercising your body and your mind will help your memory but the new study, published in the May 2012 issue of Mayo Clinic Proceedings, reports a synergistic interaction between computer activities and moderate exercise in "protecting" the brain function in people better than 70 years old.




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Computer Use and Exercise Combo May Reduce the Odds of Having Memory Loss, Mayo Clinic Finds

Combining mentally stimulating activities, such as using a computer, with moderate exercise decreases your odds of having memory loss more than computer use or exercise alone, a Mayo Clinic study shows.

Previous studies have shown that exercising your body and your mind will help your memory but the new study, published in the May 2012 issue of Mayo Clinic Proceedings, reports a synergistic interaction between computer activities and moderate exercise in "protecting" the brain function in people better than 70 years old.

Researchers studies 926 people in Olmsted County, Minn., ages 70 to 93, who completed self-reported questionnaires on physical exercise, and computer use within one year prior of the date of interview.

Moderate physical exercise was defined as brisk walking, hiking, aerobics, strength training, golfing without a golf cart, swimming, doubles tennis, yoga, martial arts, using exercise machines and weightlifting. Mentally stimulating activities included reading, crafts, computer use, playing games, playing music, group and social and artistic activities and watching less television.

Of those activities the study singled out computer use because of its popularity, said study author Yonas E. Geda, M.D., a physician scientist with Mayo Clinic in Arizona.

"The aging of baby boomers is projected to lead to dramatic increases in the prevalence of dementia," Dr. Geda said. "As frequent computer use has becoming increasingly common among all age groups, it is important to examine how it relates to aging and dementia. Our study further adds to this discussion."

The study examined exercise, computer use and the relationship to neurological risks such as mild cognitive impairment, Dr. Geda says.

Mild cognitive impairment is the intermediate stage between normal memory loss that comes with aging and early Alzheimer's disease.

Of the study participants who did not exercise and did not use a computer, 20.1 percent were cognitively normal and 37.6 percent showed signs of mild cognitive impairment.

Of the participants who both exercise and use a computer, 36 percent were cognitively normal and 18.3 percent showed signs of MCI.

Dr. Geda expects that this study will lead to more research on this topic.

The study co-authors include Ronald C. Petersen, M.D., Ph.D., and other investigators at the Mayo Clinic Study of Aging in Rochester, Minn. The study was supported by the National Institutes of Health, the Robert Wood Johnson Foundation and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program.
____________________

About Mayo Clinic

Mayo Clinic is a nonprofit worldwide leader in medical care, research and education for people from all walks of life. For more information, visit MayoClinic.com



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Match.com for Alzheimer's Caregivers, Respite Care

It's time for the members of the Alzheimer's Community to get organized around real issues that affect the lives of Alzheimer's caregivers each day.

By Bob DeMarco
Alzheimer's Reading Room

While I was in New York speaking at the Seeing Alzheimer's Differently symposium I mentioned several ideas I have about Alzheimer's and respite care. One attendee, Christopher Nadeau of the New York Memory Center, was very enthusiastic about my ideas.

After considerable thought, I now elevate this concept up to my number one idea -- Match.com for Alzheimer's caregivers.

Some of you might be familiar with Match.com, it is a dating service for singles. Basically, you describe yourself, describe what you are looking for, and include some pictures of yourself with the intention of meeting someone.

Here is how Match.com describes what they do -- Our mission is simple: to help singles find the kind of relationship they’re looking for.

How does this apply to Alzheimer's caregivers and respite?


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One of the biggest complaints, sometimes gripes, we get here on the ARR is the inability of caregivers to get a moment to themselves. A moment, let alone lets say 4 hours, or a day.

Here is a recent comment from one of our readers -- "And, when I do get a hour or (rarely) a weekend off to feel "normal" and outside the world of dementia ... I just want some normal in my life".

So I asked myself, why don't Alzheimer's caregivers team up? Yeah team up.

For example, lets say I could advertise that I am looking for a fellow caregiver to team up with to get some respite care. I read through a list of caregivers that are interested and try to find someone that seems similar to me, and has a patient in a stage of dementia similar to Dotty.

We contact each other via email, and then we get on the phone. If we agree we have a fit, we decide to meet at some public place, patient included, to discuss the possibilities.

Obviously there are two issues for each side. First, do I feel like I can trust my mother with this other caregiver, does s/he trust me.

Second, does it appear that the two patients, in my case Dotty, can get along. For me kinda simple, can they yak away with each other comfortably.

If so we have a match.

Then we start to make arrangements. First step, meet up somewhere like McDonald's for an ice cream or coffee and test it out.

Next, one caregiver agrees to take care of the other patient for let's say two hour to start. So with Dotty in tow, I pick up our counter party patient and go do something. Or, the counter party gets dropped off at our home for a couple of hours.

So one caregiver takes care of two persons (patients), and the other caregiver gets two hours off. If the arrangement works you expand the time. Imagine, four hours to do as you wish.

So in a nutshell, you have a series of dates just like you do on Match.com, starting with the meet-up, and then extending the relationship if it seems like a good fit.

Won't work you say? Well in Palm Beach County, Florida, there are about 60,000 persons in the same boat I am in.

Now for sure, someone is gonna try and crap on my parade. Count on it.

Are you already thinking about the legal liability? Well, Match has an agreement you sign that covers this. So Match.com for Alzheimer's caregivers would do the same thing.

I learned a long time, it is very costly to invent, less costly to do something that already exists and tailor it to your own needs. So we would keep this simple and use the existing model. Who knows, maybe we could get some help from Match.com. Match.com are you listening?

Don't bother crapping on my parade.

If you can add to the discussion, or if you know an organization or foundation that might help us explore this idea and get it started, shoot your comment in below, or use the contact button and send me an email.

They say there are 15,000,000 Alzheimer's caregivers. If only one percent participated that would be 150,000 people.

The bottom line here is simple and straight forward, we need to start taking care of ourselves because no one else is going to do it.

It's time for the members of the Alzheimer's Community to get organized around real issues that affect the lives of Alzheimer's caregivers each day.

Respite is a real issue.

In closing, mostly everyone makes the same complaint when it comes to respite.  I can't afford it. They don't pay for it. There is not enough money to pay for it.

Well each of us has time.

We can barter our time with another caregiver, or better yet a group of caregivers, and it won't cost us one read cent to get the respite we all need.

Go ahead, sound off below in the Add New Comment area.



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Bob DeMarco is the Founder of the Alzheimer's Reading Room and an Alzheimer's caregiver. The blog contains more than 3,511 articles with more than 297,100 links on the Internet. Bob lives in Delray Beach, FL.

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Five Ways to Prevent Influenza Complications


1. Spend three days in bed
When a man diseased with influenza has just got rid of fever and at once continues to lead an ordinary lifestyle, his immunity becomes weaker because it was lowered when it fought with viruses. Thus  viruses continue to multiply. This circle may end up with myocarditis. Besides this, low immunity is perfect environment for bacteria development. Bacteria stayed quietly in the body while immunity inhibited them, now they would multiply which may lead to tonsillitis and bronchitis. Therefore, patient should spend at least first three days in bed.

2. Do not send the temperature of 38C down
Temperature is a sign showing that body fights viruses. It is critical when temperature is above 38.5 or if at the back of high temperature occur convulsions or blood pressure jumps. Then it is necessary immediately to call an ambulance.

3. Drink three liters of liquid
A man loses up to 2 liters of liquid daily, and a man with temperature loses 1,5 times more. A man consists 80% of water and it is necessary to fulfill liquid losses to let organs and system work correctly. However, if you suffer from kidney or heart failure, you should be careful with abundant drinking in order to avoid loads on kidneys and heart.

4. Airing
Do it at least several times a day,10 - 15 minutes each time. Besides this, make wet cleaning three times a day. Dry air overdries mucous which leads to local immunity lowering and thus recovery may be delayed.

5. Three days without meat
Human body needs a lot of energy to process proteins.Now body requires energy to fight influenza, therefore food must be liquid and vegetal, for example, mashed potatoes, vegetable soups, porridges, fruits. In order to avoid allergy, consume up to 5 oranges, 1/2 glass of wineberries and half of lemon.
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Tuesday, 1 May 2012

buddi

What do you think?

Alzheimer's Reading Room

buddiband is a comfortable, discreet and waterproof wristband personal alarm that can enable people with dementia to get out and about with confidence.

buddiband has been funded and supported through the Living well with dementia Design Challenge, a competition run by the Design Council and the Department of Health to rethink life with dementia.






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