How to keep your brain young — and slow the process of ageing | Executive Living | The Australian

How to keep your brain young — and slow the process of ageing | Executive Living | The Australian

• RUTH OSTROW  December 08, 2014
  12:00AM
  

One revolutionary tip for longevity is the silly walk, a la John Cleese and Monty Python.

WE don’t have to age — or at least grow old as fast as we do. That’s
the finding of researchers in the US, where a group of specially
trained lab rats equivalent in our years to 60-year-olds became as
“young” and healthy as their 20-year-old companions.

Although our bodies will inevitably decline, scientific evidence presented at the recent international Mind & Its Potential Conference in Sydney suggests that the process can be slowed down by several decades. The things that really matter to us — vitality, libido, memory, and brain power — don’t have to change much into our 70s and 80s. And how can this be achieved? Not through hormones, surgery, vitamins or stem cell replacement.

It’s all about neurogenesis, or our ability to grow new synapses and neurons in our brains well into old age, according to University of California neuroscientist Michael Merzenich, who in Sydney shared advice on how to keep our brains young. “The King of Neuroplasticity”, Professor Merzenich, 72, says that when the brain is rejuvenated it also rejuvenates everything from our skin and organ function to capacity for pleasure and energy. The aim is to “fatten” the brain so the body doesn’t atrophy.

So how do we do this? Merzenich and other leading neuroscientists gave me their best tips for longevity. One of Merzenich’s revolutionary methods would have baby boomers and gen Xers laughing: the silly walk, a la John Cleese and Monty Python. Merzenich finds new and complicated ways to move every day to give his brain huge challenges. He says the brain loves to make decisions and solve problems, and it hates safe ways of doing things. To stay young, he says, don’t make things easy for the brain. Give it big surprises. Get out of the cave. Don’t say “I don’t do that.” Try it.

Exercise is fantastic for overall health, but to specifically grow the brain, the exercises can’t be predictable or routine. So add to the mix Rumba, Tango, gentle acrobatics, and yes, even a silly walk.
Merzenich was one of the stars of eminent psychiatrist and researcher Norman Doidge’s groundbreaking bestseller on neurogenesis and neuroplasticity, The Brain That Changes Itself. Doidge told me that “What fires together wires together”, and new synapses and pathways are forged constantly as long as the brain is used. With a bit of brain rewiring and practice, a pianist can become a concert pianist; a stroke victim can learn to talk and walk.

The bottom line, says Merzenich, is “use it or lose it”. He warns us to stop using a GPS and other gadgets for simple tasks. “Study road maps, and force yourself to remember where you’re going and the details around you. As primitive beings we survived by roaming the landscape. So listen and look around in a state of mindfulness.” Before sleep he spends five minutes in bed recalling the details he’s seen in the streets that day, in order to stimulate memory. He says to try and remember phone numbers and email addresses rather than using your mobile.

He advocates training the brain with games. Not a big fan of Sudoku or other problem-solving fads, Merzenich has a website of scientifically proven exercises. BrainHQ.com, from Posit Science, was featured in the ABC documentary Redesign My Brain, in which Todd Sampson volunteered himself as a lab rat to test the science of brain plasticity. Sampson turned into somewhat of a genius before our eyes.

Merzenich also praises meditation, which according to experiments by Richard J. Davidson of the University of Wisconsin-Madison, one of the world’s leading experts on the impact of contemplative practices on the brain, opens pathways in unused areas of the mind. Merzenich says we should learn languages, go back to university or do some courses — but to leave our comfort zone. He says try complex subjects you might not be good at, such as maths.

I followed his advice and three years ago went back to university. Despite being a technophobe, I chose to study technical matters such as video production, camera usage, and operating an edit suite. I was often in tears. But I did well, and noticed that my brain improved in other areas of memory and competency. The theory is that if you develop one part of the brain, synapses grow elsewhere.
New hobbies can challenge your brain with enough tension to create small squirts of cortisol and noradrenaline. Unlike dangerous chronic stress that comes from worry, small hits of stress hormones are excellent for stimulating the mind. Perhaps birdwatch and learn the name of new species. Stay curious. Travel is great. After achieving a new skill, reward yourself. Self-praise clinches the lessons and rewires the brain. Positive feedback promotes good habits.

US psychiatrist Stuart Brown was recently in Australia talking about the importance of play in brain health. Activities such as volleyball, running into the sea and ballroom dancing have been shown to trigger parts of the brain associated with social connection and increased intelligence.
Brown first recognised the importance of play by discovering its absence in the life stories of murderers and sociopaths. His research led him to prove that when we play and laugh, we release not only dopamine, oxytocins and other reward neurochemicals but also create synaptic connections.
Social interaction is crucial for wellbeing, according to the “father of social neuroscience”, UCLA professor Matthew Lieberman. He says without love, relationships and community, the deterioration of our health is equivalent to smoking two packets of cigarettes a day. Being with people helps us read facial signs, develop empathy and exercise our prefrontal cortex, which governs higher order functions. It was, and still is, crucial to our survival as a species. So turn off Facebook and go face-to-face.

Neuroscientists have proven that juggling increases thinking speed and one’s ability to focus. Michael J. Gelb, a respected creative thinker from the US, says that while juggling we increase our metacognition — the capacity to think about our thinking processes. This improves motor skills, spatial awareness and problem-solving capacity.

Most of us feel awkward trying new things, which is why we mostly don’t. Tal Ben Shahar, a prominent US expert in positive psychology, says we need to reframe our failures so we see them as “lessons”.

He believes we should not let fear make us shun new things. Developing comes from accepting our failures with grace. “Babies don’t just walk. They need to keep falling down, then they walk,” he reassures those of us who are embarking on a journey towards our full adult potential.


How to jump-start the grey matter

• Find new ways to move or walk every day

• Don’t stay in your comfort zone. Give the brain surprises, decisions and problems to solve

• What fires together wires together. Talent is not important. Practice any skill for 10,000 hours and you’ll master it.

• Stop using a GPS and contact book: memorise maps, phone numbers and email addresses

• Do online exercises such as BrainHQ.com from Posit Science

• Meditate for at least 20 minutes at a time, preferably morning and night

• Study something you are not good at; take up hobbies

• Read, read and read

• Play and increase your social contact

• Before going to sleep, for five minutes recall details of something like the house next door or a friend’s face

• Juggle to increase motor skills and spatial awareness

Neuroscientists speak out against brain game hype | Science/AAAS | News

Neuroscientists speak out against brain game hype | Science/AAAS | News:

ByEmily Underwood

22 October 2014 4:30 pm

 14 Comments

Aging baby boomers and seniors would be better off going for a hike than sitting down in front of one of the many video games designed to aid the brain, a group of nearly 70 researchers asserted this week in acritique of some of the claims made by the brain-training industry. 

With yearly subscriptions running as much as $120, an expanding panoply of commercial brain games promises to improve memory, processing speed, and problem-solving, and even, in some cases, to stave off Alzheimer’s disease. Many companies, such as Lumosity and Cogmed, describe their games as backed by solid scientific evidence and prominently note that neuroscientists at top universities and research centers helped design the programs. But the cited research is often “only tangentially related to the scientific claims of the company, and to the games they sell,” according to the statement released Monday by the Stanford Center on Longevity in Palo Alto, California, and the Max Planck Institute for Human Development in Berlin.

Although the letter, whose signatories include many researchers outside those two organizations, doesn’t point to specific bad actors, it concludes that there is “little evidence that playing brain games improves underlying broad cognitive abilities, or that it enables one to better navigate a complex realm of everyday life.” A similar statement of concern was published in 2008 with a smaller number of signatories, says Ulman Lindenberger of the Max Planck Institute for Human Development, who helped organize both letters. Although Lindenberger says there was no particular trigger for the current statement, he calls it the “expression of a growing collective concern among a large number of cognitive psychologists and neuroscientists who study human cognitive aging.”

“A major problem” with almost all cognitive training studies is that researchers only measure improvement in skills such as memory based on an individual task, rather than a range of tasks that represent a broad ability, Lindenberger says. Although a handful of the researchers who signed the letter are involved in brain-training game research and development themselves, all signees “draw a clear line” between improvements on a particular task and improvements in general cognitive ability, he notes. In contrast, “brain gaming companies blur this distinction,” he says, leading consumers to believe that getting better at a specific game will positively impact their cognitive abilities and competence in everyday life. “The consensus is that this is not so,” he notes.

Not all researchers agree, however. Lumping all brain game companies together and calling their claims dubious is “a classic case of throwing out the baby with the bathwater,” said Michael Merzenich, a professor emeritus of neuroscience at the University of California, San Francisco, and chief scientific officer of the brain-training company Posit Science, to The Chronicle of Higher Education, describing the statement as “irresponsible.”

Roberto Cabeza, a neuroscientist at Duke University in Durham, North Carolina, and another signatory on the statement, says that his view is that it’s fine to play such games for fun, but “if you’re doing it like a chore” to postpone cognitive aging and dementia there are other, better established methods of keeping the brain sharp, such as exercising. Cognitive improvements from exercise appear to be modest, but are still greater than any of the small, fleeting gains yet observed in studies of gaming, he says. There are also health benefits to exercise that cannot be achieved by sitting at a computer, he adds. In addition to showing that brain games have benefits that transfer to daily life, “you also have to compare it to what you could have done during those hours,” such as playing an instrument or spending time with family, he says.

For those who choose to play brain games regardless, recent research suggests that playing some video games developed solely for fun may be as effective, or more, than those developed for cognitive self-improvement. Scientists at Florida State University randomly assigned 77 undergraduates to play either Lumosity or the popular video game Portal 2, in which players take on the roles of robots to solve interactive puzzles to face off against a “lethally inventive, power-mad A.I. named GLaDOS.” After 8 hours of play, Portal 2 players scored higher than Lumosity players on three standard cognitive tests of problem-solving and spatial skill, and Lumosity players “showed no gains on any measure,” the team reported online this summer inComputers & Education.

Posted in Brain & Behavior, Education, Scientific Community, Technology

Regular marijuana habit changes your brain, study says - CNN.com

Regular marijuana habit changes your brain, study says - CNN.com:

By Saundra Young and Matthew Stucker, CNN

November 11, 2014 -- Updated 1447 GMT (2247 HKT)

STORY HIGHLIGHTS

• Study of long-term marijuana users finds they have smaller decision-making area of brain
• Chronic marijuana users had an IQ 5 points lower than those who did not use
• Some scientists say this study shows marijuana is not "a harmless drug"

(CNN) -- Using marijuana at an early age could have long-term consequences on your brain and it may even lower your IQ, according to a new study in the Proceedings of the National Academy of Sciences.

Researchers found that compared to nonusers, people who smoked marijuana starting as early as age 14 have less brain volume, or gray matter, in the orbitofrontal cortex. That's the area in the front of your brain that helps you make decisions.

"The younger the individual started using, the more pronounced the changes," said Dr. Francesca Filbey, the study's principal investigator and associate professor at the School of Behavioral and Brain Sciences at the University of Texas at Dallas. "Adolescence is when the brain starts maturing and making itself more adult-like, so any exposure to toxic substances can set the course for how your brain ends up."

Photos: History of marijuana in America

Researchers also found increased brain connectivity in chronic users. Connectivity, when different parts of the brain connect to each other, is important for adaptive learning abilities. It also helps your mind make associations. This wiring of the brain starts to deteriorate with chronic marijuana use.

Source: NYC marijuana policy to change

Colorado's booming marijuana industry

"Too much or too little of anything isn't good. There needs to be an equal balance," said Filbey.

There were 48 marijuana users enrolled in this study. All started smoking between age 14 and 30. The average age of the person enrolled in the study was 18. On average they used marijuana three times a day. Most said they had been using it for 10 years, although some had been smoking pot for three decades.

Scientists compared this group to a group of 62 nonusers of the same basic age and gender. All gave urine samples. All had an MRI scan and all went through IQ testing.

Filbey said the people who regularly used marijuana had IQ's that were five points lower, on average, than the nonusers in the study, although there is no definitive proof that marijuana alone was to blame for the lower IQ.

"While our study does not conclusively address whether any or all of the brain changes are a direct consequence of marijuana use, these effects do suggest that these changes are related to age of onset and duration of use," Filbey said.

Dr. Susan Weiss, associate director for Scientific Affairs at the National Institute on Drug Abuse said the study provides more strong evidence about the dangers of marijuana.

"This is a complex and interesting study that adds to the growing body of evidence that heavy marijuana use, particularly at a young age, is linked to significant adverse brain changes," said Weiss. "This study showed that the orbitofrontal cortex, an area involved in reward, decision making and motivation, was smaller in heavy users and that other brain circuits were enhanced, likely to compensate for the diminished function in that region. Further prospective studies are needed to clarify this, but these mounting scientific findings certainly challenge the widespread belief that marijuana is a harmless drug."

The National Institute on Drug Abuse helped fund the study.

Mason Tvert, director of communications for the Marijuana Policy Project, said marijuana use does not cause IQ loss.

"Once again, researchers have failed to find any conclusive evidence that marijuana use causes mental health problems. The researchers note their findings are nonconclusive, that they might be skewed by other factors, and that effects, if any, could be temporary, Tvert said. "The study doesn't justify keeping marijuana illegal, nor does it say anything about making it legal. There remains no doubt that marijuana is far less harmful than alcohol to the brain and to the rest of the body. The possibility that marijuana might have some harm for some people -- but might not -- is not a good reason to keep arresting and punishing hundreds of thousands of adults simply for using it."

Filbey next plans to do long-term observational studies with people who do not use marijuana to see if there are underlying factors like pre-existing conditions before exposure to THC, the psychoactive ingredient in cannabis, that could account for some of these effects.

senile dementia due to calcium deposition in the central nervous system: An interesting hypothesis.

Nige's Diet & Nutrition Blog: Calcium shift: An interesting hypothesis.:



More serendipity! Billy the k left a comment that piqued my curiosity.

From http://www.health-heart.org/acceuil.htm The atheroma 'junk' in the media is cholesterol + calcium in older people.

From Aging and calcium as an environmental factor. (emphasis mine)
"The consequences of calcium deficiency might thus include not only osteoporosis, but alsoarteriosclerosis and hypertension due to the increase of calcium in the vascular wall,amyotrophic lateral sclerosis and senile dementia due to calcium deposition in the central nervous system, and a decrease in cellular function, because of blunting of the difference in extracellular-intracellular calcium, leading to diabetes mellitus, immune deficiency and others.

I highlighted amyotrophic lateral sclerosis in red, as many Facebook friends have been having buckets of water & ice cubes tipped over themselves to raise money for research into this fatal condition.

So, what prevents & reverses migration of calcium from hard tissues to soft tissues?
Clue: It carboxylates osteocalcin in bone matrix Gla proteins. Yes, it's Vitamin K2.

See also Calcium, parathyroids and aging.

A Bold New Experimental Treatment for Alzheimer's Dementia | Psychology Today

A Bold New Experimental Treatment for Alzheimer's Dementia | Psychology Today:

 "Ketone esters prove astonishingly effective in a single case study."

Alzheimer’s Dementia is a neurodegenerative condition that affects five million Americans in 2014. In fact, a third of seniors will die with the disease or another type of dementia (1). The cause is unknown, but over time the brain cells begin to fill up with waste products and die, leading to an inflammatory reaction in the brain that seems to add to the problem and accelerate the disease. The only FDA-approved treatments are certain medicines of the class of cholinesterase inhibitors. These medicines slow down the breakdown of the neurotransmitter acetylcholine, helping damaged brain cells work better for a time. These medicines do not stop the progression of the disease, but in some cases can slow it.

Given the awful burden on families, the poor prognosis of individuals who have the disease, and the absolute cost of the illness (in terms of unpaid care by family members, estimated at 220 billion dollars for 2013 by the Alzheimer’s Association), a lot of time and research attention has been spent on finding causes, reducing risks, and looking for cures.

Some time ago I wrote an article about one of these lines of inquiry,ketogenic diets and Alzheimer’s disease.  It explored how a certain product of metabolism that comes from fasting or from eating very high fat diets, calledketones, might improvecognition in the case of mild cognitive impairment or dementia. Ketones can be used by most cells of the brain to make energy. Why would they have an advantage over our typical brain fuel, glucose, in cases of dementia? Well, it’s complicated, but the evidence suggests ketones can be burned more efficiently with fewer waste products, keeping the stress off the damaged brain cells.

The theory seemed reasonable to Mary Newport, a physician whose husband was diagnosed with Alzheimer’s years ago. She decided to put him on  ketogenic diet (their story is available at their website, coconut ketones), and he had significant improvement within a couple of months. If you follow the link to the website, you can see a dramatic improvement in Mr. Newport’s ability to draw a clock within 14 days. I’m aware of a few other cases where patients went from serious cognitive problems, on the verge of not being able to be cared for at home, to being able to wash, dress, and feed themselves and having conversations again with ketogenic diets. 

In the past, ketogenic diets were extremely strict (they have to be very low carbohydrate, less than in a banana) and also low protein, but with the inclusion of certain foods and products like coconut oil and medium chain triglyceride oil, you can double or even triple the amount of allowed carbohydrate, making for a more flexible and ultimately safer diet. Ketogenic diets have been followed for years, particularly by children with intractable seizures as treatment, but there are few scientific studies of adults trying them for extended periods. Such diets may lead to increased risk of kidney stones, nutrient deficiencies (particularly the very strict diets), reduced thyroid function, and weight loss. While most adults in America might welcome weight loss, poor eating habits and weight loss can be devastating for someone with dementia who might not be able to feed his or herself. 

Mary Newport, considering the options of having her husband living in a care facility and having very poor quality of life versus attempting a ketogenic diet using supplemental coconut/MCT oil and having him be much more functional and live at home, decided to take the risk. He improved in cognitive function, gait, and many activities of daily living, and serial MRIs over this time showed no progression of the disease. However, it turns out the benefits of the ketogenic diet didn’t last forever.

According to a new paper from Alzheimer’s and Dementia, A new way to produce hyperketonemia: Use of ketone ester in a case of Alzheimer’s disease, Mr. Newport took a turn for the worse in 2010 while participating in a clinical trial for a drug for Alzheimer’s Dementia. He went back to square one, losing interest in yard work and requiring step by step instructions to dress himself. His wife, Dr. Newport, sought a different way to induce a higher level of ketosis in her husband. Using coconut/MCT oil supplements in normal, healthy adults will raise ketone levels in the blood from 0.09 mM to 0.3-0.4 mM immediately, and over time one can get 10 times those levels sticking to the supplement and a low carbohydrate diet. Ingestion of 50 grams of a supplement called a ketone ester can double those levels within an hour, leading to 6-7mM concentrations one can only find in humans with prolonged fasting. Ingesting the supplement every 3-4 hours can maintain these high levels. 

Ketone esters are in a class of supplements called “generally recognized as safe” or GRAS by the FDA. They are expensive, difficult to find, and taste nasty (I’ve smelled some, and it was a bit like salty urine). There are no long term studies of the safety of these supplements in humans, though high ketone levels were maintained in severely obese, fasting patients for 6-8 weeks and there seemed to be no side effects. The main risk might be an exacerbation of gout, but truly, the long term consequences are unknown. For someone with dementia facing an inevitable downward spiral and life in a long term care facility, the question of benefits versus risk is a different calculation than in someone without that condition.

After a few days of escalating doses, Mr. Newport was brushing his own teeth, spontaneously dressing and bathing himself again, had improvements in mood, and was able to recite the alphabet. After 6-8 weeks, his memory improved and he started to do yard work again. After 20 months, he maintained definite improvement, with his cognitive function seeming to wax and wane with rising and falling ketone levels in his blood.

While this report is just a single case study, it does merit more clinical investigation. Given the severity and cost of the disease, the possibility of a far more effective treatment than what we currently have must be explored further.  In addition, dementia is not the only intractable and devastating brain illness that could be helped by the administration of ketone esters. People with epilepsy, bipolar disorder, schizophrenia, autism, andtraumatic brain injury might also benefit. The only way to know for sure is to do the research.

Brain cleaning - One more reason to get a good night’s sleep - YouTube

Published on 13 Oct 2014 

The brain uses a quarter of the
body's entire energy supply, yet only accounts for about two percent of
the body's mass. So how does this unique organ receive and, perhaps more
importantly, rid itself of vital nutrients? New research suggests it
has to do with sleep.

Change Your Movement, Change Your Brain | Psychology Today

Change Your Movement, Change Your Brain | Psychology Today:

We can use our bodies to help us think better.

Published on October 22, 2014 by Steve Sisgold in Life in a Body

Being aware of how you move your body can help you think more clearly and turn up the dial on your brainpower. Research shows that the brain can take cues from body movements to understand and solve complex problems.

In 2009, University of Illinois psychology professor Alejandro Lleras, along with Laura Thomas of Vanderbilt University, conducted a study on problem solving and body movement. They set out to test if a person's ability to solve a complex problem could be influenced by how he or she moves. They tested fifty-two University of Illinois students. The results showed that body motion could, indeed, affect higher order thought and that complex thinking can be enhanced by body awareness.

Lleras and Thomas reported, “People tend to think that their mind lives in their brain, dealing in conceptual abstractions, very much disconnected from the body. This emerging research is fascinating because it is demonstrating how your body is a part of your mind in a powerful way. The way you think is affected by your body and, in fact, we can use our bodies to help us think.”

This study confirms what I often see in my sessions. A client will be stuck in some unproductive thought loop or knee-jerk reaction. They become fuzzy and confused as to what is actually occurring right in front of them. I redirect their attention to the movements happening in their body, which consistently opens a window to solutions that aren’t being arrived at by the mind alone. Clients find the attention-shift consistently generates new insight, enhances creative thinking, and resiliency. They just seem smarter once they are conscious of how their body moves.

We have the ability and hardwiring to usemovement awareness to discover and break the neural nets that work against us. Psychiatrist Dr. Jeffrey Schwartz, a researcher in the field of neuroplasticity, agrees. In his book The Mind and the Brain, he says, “Humans are neural electricians. We can take charge of our brain function. We are not restricted to working with existing wiring. We can run whole new cables through our brain.”

Make a Move

Open your arms wide, or raise your hand in a high-five, or mimic Steve Martin doing his “wild and crazy guy” shoulder shimmy. Sync that movement with your breathing and notice how that changes your mood. How did that feel? Do you notice a change in your thinking or energy level? Make that choice to pause and make expansive moves as often as you can. It can make a big difference in how you feel, how you make decisions or react to a situation. To discover more about your body and movement awareness go to http://wholebodyintelligence.com/bq_assessment

Nobel discovery - window onto Alzheimer's disease | Reuters

Nobel discovery opens window onto Alzheimer's disease | Reuters:

LONDON Mon Oct 6, 2014 6:32pm EDT

1 COMMENTS

Professor John O'Keefe poses in his laboratory at University College London (UCL), in London October 6, 2014.

CREDIT: REUTERS/SUZANNE PLUNKETT

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(Reuters) - The discovery of cells in the brain that act as the body's internal global positioning system, which won three scientists the Nobel Prize for medicine on Monday, opens an intriguing new window onto dementia.

Since these spatial cells are among the first to be hit in Alzheimer's and other forms of dementia -- explaining why sufferers often lose their way -- understanding how they are degraded should shed important light on the disease process.

That is the belief of British-American researcher John O'Keefe, winner of the 2014 prize alongside Norwegians May-Britt and Edvard Moser, who plans to take his research to the next level as director of a new brain institute in London.

"We're now setting up to do much more high-tech studies where we hope to follow the progression of disease over time," he told reporters after hearing he would share the 8 million Swedish crowns ($1.1 million) prize.

"This will give us the first handle as to when and where the disease starts and how we can attack it at a the molecular and cellular level."

The battle against Alzheimer's has been long and frustrating. Global cases of dementia are expected to treble by 2050, yet scientists are still struggling to understand its basic biology and drug development is littered with failures.

The work by O'Keefe and the Mosers will not lead to immediate breakthroughs but by explaining how cells function -- and then fail to function -- in two very specific regions of the brain it is seen as vital for unpicking how Alzheimer's develops.

Dementia, of which Alzheimer's is the most common form, already affects 44 million people worldwide and that number is set to reach 135 million by 2050, according to Alzheimer's Disease International, a non-profit campaign group.

"Understanding how the healthy brain functions, especially areas of the brain crucial to learning and memory, is incredibly important in understanding what changes occur during conditions such as Alzheimer’s disease," said Doug Brown, director of research and development at Britain's Alzheimer's Society.

The Nobel Prize winners' work on the brain's navigation system stretches back more than 40 years, but more recently scientists have developed powerful new tools for studying brain circuits that O'Keefe plans to put to work at the new London research institute where his is director.

The first of more than 150 scientists will start work at the Sainsbury Wellcome Centre for Neural Circuits and Behaviour at University College London next year, using state-of-the-art lasers, molecular biology and computational modeling to explore the brain's intricate wiring.

"It's a very exciting time," O'Keefe said.

The Group of Eight leading industrial countries set a goal last December of finding a cure or effective treatment for dementia by 2025.

It is a decade since the last drug was approved to treat Alzheimer's, and there is still no treatment that can slow the progression of the disease, with current drugs only easing some of the symptoms of the disorder.

"We all know there is a time bomb there," O'Keefe said. "We are starting to get a handle on it but that doesn't mean it is going to turn into a cure in the immediate future."

(This story has been refiled to fix typo in first paragraph; no other changes to text)

(Reporting by Ben Hirschler, Ediitng by Angus MacSwan)

People with dementia remember emotion

People with dementia remember emotion



OCTOBER 07, 2014 6:23PM

People with dementia remember the feelings associated with an event for a longer time, a study says. Source: AAP

ALTHOUGH people with Alzheimer's disease forget things quickly, they can remember the feelings associated with an event for a longer time, a US study has found.

ALZHEIMER'S patients and healthy people were shown 20-minute film sequences which were either happy or sad for a study carried out by the University of Iowa. Five minutes later the study participants were questioned about what they could remember of the films.

As might be expected, the Alzheimer's sufferers remembered significantly less of the film content than did the healthy participants. Some didn't even remember that they had seen a film.

However, the feelings of sadness or happiness that had been aroused by the films remained for up to half an hour after the showing. It was particularly striking that the feeling of sadness stayed with the dementia sufferers longer, the less well they were able to remember the film.

The researchers concluded with an encouraging message for relatives and loved ones of dementia sufferers: even though a sufferer might not be able to remember a visit, the positive feelings from one can still persist long after.

Nitric Oxide and Neuroactivity – The Big Picture

Integrated Supplements Whey Isolate Creapure Creatine Magnesium:

Part 3

Articles in this Series:
Nitric Oxide – The Big Picture – Part 1 
Nitric Oxide – The Big Picture – Part 2 
Nitric Oxide – The Big Picture – Part 3 

If the human brain was so simple that we could understand it, we would be so simple that we couldn't.
–Emerson Pugh, Physicist

Ask a cardiologist about the effects of nitric oxide, and there’s a good chance you’ll hear about the chemical’s role in dilating blood vessels, lowering blood pressure, and supporting cardiovascular health.

Ask a neurologist about nitric oxide, and you’ll likely to hear about the widespread cellular damage this chemical can cause, and how an excess of nitric oxide in the brain is now thought to be a major contributing factor to degenerative neurological diseases like Alzheimer’s disease, Parkinson’s disease, and ALS.

And, ask an oncologist for yet a third opinion, and you may hear about nitric oxide’s role in either suppressing tumor growth – as a potent tumor–killing agent of the immune system; or, conversely, its role in stimulating tumor growth by triggering angiogenesis, the formation of the new blood vessels tumors need to survive.

So, clearly, nitric oxide has many varied effects within our bodies – some beneficial, and some very harmful. This is the fundamental reason why so many attempts to manipulate nitric oxide levels, either pharmacologically or nutritionally, have met with failure.

As relates to the cardiovascular system, for example, it was initially thought that increasing nitric oxide levels would be the key to correcting what was simplistically assumed to be a “deficiency” of nitric oxide in cardiovascular disease. But this approach is quickly being abandoned, as a myriad of unforeseen (and sometimes fatal) side effects have accompanied nitric oxide–boosting therapies.

Of course, some nutritional supplement companies, and some health practitioners (whose products and recommendations lag decades behind the actual research) continue to recommend that we indiscriminately increase our nitric oxide levels with various nitric oxide–boosting concoctions. But the flaws inherent in such an approach are now well–documented, even if not yet well–publicized.

In light of what we now know about the often harmful effects of nitric oxide, it seems that we’ll want to do everything we can, not merely to increase nitric oxide levels, but to keep nitric oxide production under tight control throughout the body.

A Brief Review

When produced, nitric oxide rapidly reacts with a chemical called superoxide, to form a particularly damaging chemical called peroxynitrite. It’s now believed that this process is largely to blame for many of the harmful effects of nitric oxide.

When nitric oxide–boosting therapies are employed – like the use of the amino acid precursor to nitric oxide, arginine – or the nitric oxide pro–drug, nitroglycerin, the production of peroxynitrite increases right along with nitric oxide itself. And the result has often been a short–term benefit, marred by longer–term harm.

Recent research has found, however, that we may be able to give our nitric oxide metabolism a nutritional “tune–up,” without increasing our burden of harmful nitric oxide byproducts. The answer lies not in “boosting” nitric oxide, but in supplying our body with the nutrients needed to metabolize nitric oxide safely and efficiently.

In the last Integrated Supplements Newletter, we looked at nutritional factors like folic acid, Vitamin B6, and Vitamin B12 which may reduce homocysteine and simultaneously protect the fragile nitric oxide cofactor, called tetrahydrobiopterin.

We saw how antioxidant nutrients like Vitamin E, Vitamin C, selenium, and whey protein isolate may help to reduce the oxidative stress which constantly threatens nitric oxide metabolism.

We even saw how cocoa flavonols and creatine monohydrate may exert especially beneficial effects on nitric oxide metabolism.

Building on these strategies, we’ll now look at other nutritional factors which will help support proper nitric oxide metabolism in the cardiovascular system and beyond.

This Is Your Brain on Nitric Oxide

In the late 1980’s, an iconic public service announcement on television depicted a frying egg, while an actor sternly warned an entire generation of impressionable Americans, “This is your brain on drugs.” And while this PSA offered a powerful visual metaphor of the effects certain drugs can have on brain function, it may serve us well to look a little deeper into the molecular biology of the matter.

It turns out that much of the toxicity associated with neuro–active drugs is ultimately due to the actions of nitric oxide. In fact, the chemical inhibition of the enzymes which produce nitric oxide has been shown to abolish the toxicity associated with both methamphetamine and cocaine.

Study Link – Nitric oxide (NO) synthase inhibitors abolish cocaine–induced toxicity in mice.

Quote from the above study:

Repeated administration of cocaine (45 mg/kg/day) for 7 days to Swiss–Webster mice resulted in a progressive increase in the convulsive response to cocaine and augmentation in lethality rate. Pretreatment with the nitric oxide (NO) synthase inhibitors, L–NAME (100 mg/kg/day) or NO–Arg (25 mg/kg/day), prior to cocaine administration completely abolished the sensitization to the convulsive and lethal responses to cocaine. These findings suggest a role for NO in cocaine–induced toxicity.

Study Link – Role of nitric oxide in methamphetamine neurotoxicity : Protection by 7–nitroindazole, an inhibitor of neuronal nitric oxide synthase.

Quote from the above study:

These findings indicate a role for nitric oxide in methamphetamine–induced neurotoxicity and also suggest that blockade of NOS may be beneficial for the management of Parkinson's disease.

And you don’t have to be a drug–user to be susceptible to the neurotoxic effects of nitric oxide. The damage caused by nitric oxide and its metabolites has been very strongly linked with age–related brain degeneration, and disorders such as Parkinson’s disease, ALS, and Alzheimer’s disease.

Study Link – Nitric oxide neurotoxicity.

Quote from the above study:

NO has many roles in the central nervous system as a messenger molecule, however, when generated in excess NO can be neurotoxic. Excess NO is in part responsible for glutamate neurotoxicity in primary neuronal cell culture and in animal models of stroke. It is likely that most of the neurotoxic actions of NO are mediated by peroxynitrite (ONOO−), the reaction product from NO and superoxide anion.

Study Link – Widespread Peroxynitrite–Mediated Damage in Alzheimer's Disease.

Quote from the above study:

These findings provide strong evidence that peroxynitrite is involved in oxidative damage of Alzheimer's disease.

Studies have found, as well, that mice bred to be deficient in one of the nitric oxide–producing enzymes had decreased mortality, and were significantly protected from many of the manifestations of Alzheimer’s disease:

Study Link – Protection from Alzheimer's–like disease in the mouse by genetic ablation of inducible nitric oxide synthase.

Quote from the above study:

Deficiency of iNOS substantially protected the AD–like mice from premature mortality, cerebral plaque formation, increased ß–amyloid levels, protein tyrosine nitration, astrocytosis, and microgliosis. Thus, iNOS seems to be a major instigator of ß–amyloid deposition and disease progression. Inhibition of iNOS may be a therapeutic option in AD.

And, in addition to degenerative brain diseases, nitric oxide has also been implicated in other neurological disorders such as migraine headaches:

Study Link – Nitric oxide is a key molecule in migraine and other vascular headaches.

Study Link – Nitric oxide–induced headache in patients with chronic tension–type headache.

Study Link – Nitric oxide supersensitivity: a possible molecular mechanism of migraine pain.

The following study even found that those with migraine headaches may be at increased risk of developing Alzheimer’s disease later in life. The common role of nitric oxide in each disorder helps to explain why.

Study Link – Risk factors for Alzheimer's disease: a population–based, longitudinal study in Manitoba, Canada.

Quote from the above study:

The association of AD with a history of migraines and occupational exposure to defoliants/fumigants is of particular interest because these are biologically plausible risk factors.

Nitric oxide is even suspected to play a major role in the development of the chronic ringing in the ears known as tinnitus:

Study Link – The NO/ONOO– cycle as the etiological mechanism of tinnitus.

Study Link – Pharmacological models for inner ear therapy with emphasis on nitric oxide.

At first glance, it may seem ironic that nitric oxide, a compound deemed so beneficial for cardiovascular health, could be so universally maligned for its harmful role in neurological health.

But of course, we now know that there is much more to nitric oxide metabolism than was once assumed. Though a certain amount of nitric oxide is necessary for cardiovascular function, any excess can be decidedly harmful. As we’ll see, the same general principles (ensuring the proper metabolism of nitric oxide) apply when addressing nitric oxide metabolism in the brain and in the neurological system.

Nitric Oxide – Inflammatory Chemical

One of the ways in which nitric oxide can be produced in the body is via an enzyme known as inducible nitric oxide synthase (iNOS). Immune cells, called macrophages, contain iNOS, and can produce nitric oxide to destroy invading viruses or bacteria, or under other conditions of stress and trauma. This means that nitric oxide is an integral part of our bodies’ immune system and inflammatory response, but it also means that the production of nitric oxide by macrophages can very easily spiral out of control.

Unlike endothelial nitric oxide synthase (eNOS, the form of nitric oxide synthase which produces NO in the blood vessels), iNOS can churn out massive amounts of nitric oxide virtually non–stop. This excess nitric oxide (and the metabolites produced from it) can be particularly harmful to the delicate, lipid–rich structures of the brain. And, as we now know, inflammation and tissue damages often proceeds in a vicious downward spiral, perpetuating even more tissue damage and inflammation. This is a major reason why nitric oxide production needs to be kept under control in conditions of stress, aging, and disease.

As we mentioned in previous issues of the Integrated Supplements Newsletter, we ideally want any inflammatory response of our immune system to be “short and sweet” – sufficient enough to deal with the stress at hand, but not excessive enough to cause a self–perpetuating spiral of tissue destruction.

Reducing Inflammation Safely

It’s now widely accepted that all degenerative diseases share the common thread of excessive and uncontrolled inflammation – including the over–production of nitric oxide. But, for as many anti–inflammatory foods, drugs, and supplements as we have at our disposal, reducing systemic inflammation safely still takes a bit of biochemical know–how.

For instance, it’s well–documented that some “anti–inflammatory” strategies may ultimately be destined to do more harm than good. The dangerous side effects associated with the wildly popular COX–2 inhibitor medication, Vioxx® are a chilling reminder of this; and, in the May 2008 edition of the Integrated Supplements Newsletter, we saw how even many of the “anti–inflammatory” fats often recommended by the health–food and nutritional supplement crowd (omega–3s, for example) may predispose us to tissue fragility and destruction when consumed in excess.

On the other hand, when we attempt to reduce inflammation in a physiologically sound manner, we’ll find that the pieces of the puzzle fit together in such a way as to actually give us far–reaching health benefits.

As relates to nitric oxide, we’ll find that some nutritional substances can serve to reduce the excess production of inflammatory nitric oxide produced by the immune system, while at the same time improving the bioavailability of the nitric oxide produced within the cardiovascular system. The most important nutrient offering such a two–pronged benefit is likely to be the often overlooked mineral, magnesium.

Magnesium and Nitric Oxide

According to data from the United States Department of Agriculture, a full 68% of Americans fail to consume the minimum recommended amount of magnesium each day; and a stunning body of scientific evidence indicates that very few nutritional deficiencies are as widespread, or as deadly, as magnesium deficiency.

Many people know that the electrolyte mineral, magnesium, is involved in “electrical” functions of the body like the heartbeat, and nerve impulses, but very few people realize that the presence of a magnesium deficiency leads to an absolutely massive increase in various markers of systemic inflammation.

The list of biological substances increased in the body when magnesium is deficient reads like a “who’s–who” of inflammatory chemicals. C–reactive protein, substance P, cytokines, prostaglandins, histamine, and of course, nitric oxide all become elevated when magnesium levels are sub–optimal.

Study Link – The nerve–heart connection in the pro–oxidant response to Mg–deficiency.

Quote from the above study:

In rodent models of dietary MgD [magnesim deficiency], a significant rise in circulating levels of proinflammatory neuropeptides such as substance P (SP) and calcitonin gene–related peptide among others, was observed within days (1–7) of initiating the Mg–restricted diet, and implicated a neurogenic trigger for the subsequent inflammatory events; this early "neurogenic inflammation" phase may be mediated in part, by the Mg–gated N–methyl–D–aspartate (NMDA) receptor/channel complex. Deregulation of the NMDA receptor may trigger the abrupt release of neuronal SP from the sensory–motor C–fibers to promote the subsequent pro–inflammatory changes: elevations in circulating inflammatory cells, inflammatory cytokines, histamine, and PGE(2) levels, as well as formation of nitric oxide, reactive oxygen species, lipid peroxidation products, and depletion of key endogenous antioxidants. Concurrent elevations of tissue CD14, a high affinity receptor for lipopolyssacharide, suggest that intestinal permeability may be compromised leading to endotoxemia. If exposure to these early (1–3 weeks MgD) inflammatory/pro–oxidant events becomes prolonged, this might lead to impaired cardiac function, and when co–existing with other pathologies, may enhance the risk of developing chronic heart failure.

And, as relates specifically to nitric oxide, it’s interesting to note that magnesium deficiency has the effect of increasing the “inflammatory” nitric oxide (produced by iNOS), rather than the cardioprotective type produced by eNOS (called constitutive NOS in the following study):

Study Link – Magnesium deficiency in rats induces a rise in plasma nitric oxide.

Quote from the above study:

Magnesium deficiency in rats leads to an oxidative stress involving an increased production of radical oxygen species. The present study was designed to examine the effect of experimental magnesium deficiency on plasma nitric oxide (NO) level and nitric oxide synthases (NOS) activities in rats. The data show that the concentration of NO is markedly increased in plasma of magnesium–deficient rats. This rise in plasma NO results from activation of inducible nitric oxide synthase (iNOS) rather than of the constitutive form (cNOS) of the enzyme. These data are in agreement with previous observations indicating that inflammation occurs during magnesium–deficiency and provide an additional cause of oxidative lesions through formation of peroxynitrite from nitric oxide and superoxide anion.

Study Link – Magnesium–deficient medium enhances NO production in alveolar macrophages isolated from rats.

Quote from the above study:

These results suggest that Mg(2+) deficiency enhances NO production via iNOS by alveolar macrophages.

And knowing that nitric oxide is largely responsible for much of the brain deterioration of Alzheimer’s, it’s interesting to find that there may be a direct correlation between magnesium status and the progression of the disease. The following study found that as magnesium status worsened so too did the progression of Alzheimer’s disease as evidenced by falling scores on cognitive tests:

Study Link – Serum magnesium level and clinical deterioration in Alzheimer's disease.

Quote from the above study:

Our data suggest that there is a relationship between serum Mg levels and the degree of Alzheimer's disease and that the determination of the Mg level at various stages may provide valuable information in further understanding the progression and treatment of Alzheimer's disease.

Because of the multiple roles magnesium plays in reducing systemic inflammation and excessive nitric oxide production, a lack of magnesium can exert effects at every level of biological functioning. As evidence, the widespread magnesium deficiency caused by our modern diet is known to be a major factor in the increasing prevalence of all degenerative diseases of aging, including not only brain diseases, but heart disease, diabetes and cancer as well.

And considering the fact that so few individual foods contain high amounts of magnesium (and the fact that multivitamins never contain sufficient amounts) it’s safe to say that a stand–alone magnesium product is often the single most important nutritional supplement a health–conscious person can take. But, even magnesium alone may not be enough to fully rectify a magnesium deficiency. Other nutritional factors, such as selenium, potassium, vitamin B6, and vitamin D, are also needed for proper magnesium absorption and metabolism.

Study Link – The multifaceted and widespread pathology of magnesium deficiency.

Quote from the above study:

Unfortunately, Mg absorption and elimination depend on a very large number of variables, at least one of which often goes awry, leading to a Mg deficiency that can present with many signs and symptoms. Mg absorption requires plenty of Mg in the diet, [selenium], parathyroid hormone (PTH) and vitamins B6 and D.

Curcumin and Nitric Oxide

In addition to correcting outright nutritional deficiencies, there are many other steps we can take to reduce the inflammatory over–production of nitric oxide.

It seems that nature, in her infinite wisdom, has supplied us with many plant–based anti–inflammatory substances which may impart particularly powerful effects when it comes to scavenging nitric oxide. One of the most notable of such substances is the yellow/orange pigment from turmeric, called curcumin.

Turmeric, a member of the ginger family, is a spice which has been long–used in Indian and Chinese cuisine, and respective systems of medicine. Recent research has uncovered that many of the health–promoting benefits traditionally associated with turmeric may be attributable specifically to curcumin; and interestingly, we find that curcumin may act as a powerful scavenger of nitric oxide.

Study Link – Nitric oxide scavenging by curcuminoids.

Quote from the above study:

The results indicate curcumin to be a scavenger of nitric oxide. Because this compound is implicated in inflammation and cancer, the therapeutic properties of curcumin against these conditions might be at least partly explained by its free–radical scavenging properties, including those toward nitric oxide.

And, although some research indicates that curcumin may be poorly absorbed, there’s reason to believe that curcumin and turmeric may exert their health–benefits despite this fact. Even though turmeric contains only about 3% curcumin at the most, and curcumin is likely to be poorly absorbed, preliminary studies conducted in India (where turmeric is very widely used in cooking) have shown some of the lowest levels of Alzheimer’s disease ever recorded – results which held true for both rural and urban communities:

Study Link – Incidence of Alzheimer's disease in a rural community in India: the Indo–US study.

Quote from the above study:

These are the first AD incidence rates to be reported from the Indian subcontinent, and they appear to be among the lowest ever reported. However, the relatively short duration of follow–up, cultural factors, and other potential confounders suggest caution in interpreting this finding.

Study Link – Prevalence of dementia in an urban Indian population.

Quote from the above study:

In the population surveyed, the prevalence of AD and other dementias is less than that reported from developed countries but similar to results of other studies in India.

If these results have anything to do with turmeric consumption, the chances are good that most of us can benefit from simply adding more turmeric–rich meals to our diet. Curcumin extracts do exist as nutritional supplements, but they are very costly relative to the very inexpensive spice, turmeric.

And research indicates that we can find many other inexpensive ways to reduce the inflammatory effects of nitric oxide as close as the local grocery store. Antioxidant compounds in (green and black) tea, coffee, red wine, cocoa, and pomegranate have all been shown to protect against the inflammatory over–production of nitric oxide.

Study Link – Protection against nitric oxide toxicity by tea.

Study Link – The coffee diterpene kahweol suppress the inducible nitric oxide synthase expression in macrophages.

Study Link – Synergy between ethanol and grape polyphenols, quercetin, and resveratrol, in the inhibition of the inducible nitric oxide synthase pathway

Study Link – Effects of an aqueous extract of cocoa on nitric oxide production of macrophages activated by lipopolysaccharide and interferon–gamma.

Study Link – Pomegranate juice protects nitric oxide against oxidative destruction and enhances the biological actions of nitric oxide.

As we’ve seen in this series of articles, nitric oxide metabolism can be more than a bit complicated. And despite a frenzy of conflicting nitric oxide research, we’ve seen the unfortunate tendency of both the medical community and the nutritional supplement industry to “jump the gun”, and rush to market products based upon dangerous misinterpretations of the scientific evidence.

But, yet again, only as we look deeper into the research, does the big picture become clear. Only then can we address fundamental biological imbalances, and not merely symptoms or biological markers.

And again, we see that carefully–chosen, time–tested natural foods and nutrients offer us the greatest long–term benefit – with little to no risk. The nutrients and foods mentioned in this series of articles are the substances the human body has always needed to support health, but they are often the substances most conspicuously lacking from our modern food supply.

In the final analysis, nitric oxide is just another example of a biological chemical whose actions can seem baffling and paradoxical when we forget to look first to nature for the answers. Only when we remember our role as a part of nature, will the pieces of the puzzle fall neatly into place.