U.S. Launches National War on Alzheimer's

No Mention of Dental Amalgam Ban in Mandate from Feds

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  Doug Kapustin, for USA TODAY
  Carol and Bob Blackwell take a daily walk near their suburban Virginia home.

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Doug Kapustin, for USA TODAY

Carol and Bob Blackwell take a daily walk near their suburban Virginia home.

GREAT FALLS, Va. — When doctors told Carol Blackwell that her husband — her best friend and the love of her life — had Alzheimer's disease, they assured her "a cure was just around the corner."

Bob Blackwell was 64, recently retired from the CIA as an analyst on the former Soviet Union and Europe and still functioning normally. "He was brilliant then."

That was five years ago.

"Here we are, and there's no cure and no promise of a cure," Carol says, sitting in her family room, eyes wet with tears.

She is Bob's primary caregiver, and the last couple of months have been "tough," she says. There are days when Bob doesn't know she's his wife. "I've been through a lot of grieving," she says. "I know it's too late for a cure for Bob, the disease has moved into too many parts of his brain, but I'm praying for my children and grandchildren. We have to find a cure."

Growth of Alzheimer's

Projected number of people 65 and over in the U.S. with Alzheimer's disease* in millions.
* Does not include early onset
** Projected

Carol will be paying close attention to government meetings Tuesday and Wednesday in Washington where Health and Human Services officials are gathering with other medical experts to discuss the framework for the first national plan to fight the disease. The No. 1 goal stated in the early draft of the National Alzheimer's Project Act is to prevent and effectively treat Alzheimer's by 2025. Although the funding levels have not been determined, disease experts compare the multi-agency federal approach of NAPA to the wars on heart disease and cancer.

Alzheimer's, which is a form of dementia that causes progressive loss of intellectual and social skills, is the only disease among the top killers for which there is no prevention, cure or treatment that will slow its progression.

"I think the potential impact of this plan is huge," says Ron Petersen, chairman of the NAPA non-federal advisory council and director of the Mayo Clinic's Alzheimer's Disease Research Center. "Given the economic problems, it's a bit of a challenge, but this is our chance to make a bold statement."

President Obama signed NAPA into law last January. Experts have spent a year formulating the framework for the plan, and the final draft is due on the desk of HHS Secretary Kathleen Sebelius this month or early February. George Vradenburg, a member of the research committee with Petersen, says the early plan is good overall but needs to move faster: "It's the first time the government has talked about a time-based goal to stop Alzheimer's. I'm going to urge we accelerate the time. I'm committed to 2020."

The task before them is an urgent one. The disease runs in families — Bob Blackwell's grandmother died from it, and his mother has it — and affects more than 5 million people in the USA. About half the people 85 and older have the disease. The number of cases, including early-onset Alzheimer's like Bob Blackwell's, is likely to triple by 2050 as the Baby Boomers grow old, at which point annual costs are likely to soar to $1 trillion. The illness costs the Medicare and Medicaid programs $130 billion a year.

"My mother-in-law has been in a facility for 15 years," Carol Blackwell says. "In 2005, after her husband died … she'd used up all her money (for care), and Bob had to file for Medicaid for her. She's been living at the government's expense since then. We have to prevent those costs down the road."

Carol and Bob Blackwell have marched on Capitol Hill with members of the Alzheimer's Association to push for more research dollars, funding that falls behind many other diseases. In a survey last year by the Harvard School of Public Health, nearly 70% of respondents said the government should increase spending for Alzheimer's research.

Changing perceptions

Harry Johns, president of the Alzheimer's Association, says the research amount needs to grow to at least $2 billion. He was in charge of strategic initiatives for the American Cancer Society before taking this post.

"People have different opinions about the success of the war on cancer," Johns says, "but people are living longer (with cancer) and have hope. There is better diagnosis and drugs for some cancers. NAPA has the potential to also change the course of a disease."

He aims to eliminate the stigma. "Back in the 1960s, people didn't talk about it," he says. "They were ashamed of it and wanted to hide it. We need to change that public discussion."

He is hopeful that new, high-profile faces of Alzheimer's will help bring that about and put the national spotlight on the disease as Betty Ford did for breast cancer. Both Tennessee women's basketball coach Pat Summitt and singer Glen Campbellannounced last year they have Alzheimer's and are continuing to work for as long as possible.

"No (celebrity) has gone public with Alzheimer's since Ronald Reagan, and when he announced it, we didn't see much of him anymore," Johns says. "Pat and Glen going public have been watershed moments for the cause."

Finding a drug that would slow the progress of Alzheimer's for just five years would greatly reduce government costs and the toll on families, Johns says: "There really isn't another disease that has this kind of impact. It is disproportionately under-invested."

Where the money will come from is the key question. The National Institutes of Healthoversees the bulk of the groundbreaking research against diseases. Francis Collins, director of the NIH, told USA TODAY in July that the agency's budget was cut $321 million in the fiscal year, the second time in 40 years the NIH has had a budget that was less than the preceding year.

The government spent about $500 million in 2011 on research for Alzheimer's and related dementias. By comparison, approximately $521 million was spent on complementary and alternative medicine and $823 million on obesity. Cancer drew a $6 billion check in 2011 for starters, with additional funding allocated for breast, brain and lung cancers.

"We're still in the process of getting feedback and making recommendations about funding levels," Petersen says. "But the plan will have to be in tune with the fiscal realities everyone is facing right now."

Petersen expects HHS to finalize the plan for NAPA by late April in time for a research summit in May at the National Institute on Aging.

Encouraging progress

Petersen is encouraged by progress in the past five years. Researchers identified genes associated with the disease and have a clearer idea of when the disease begins — often as early as 10 or 15 years before symptoms appear — and what causes it. They have discovered some of the disease's biomarkers in a variety of tests, potentially making diagnosis possible years before the disease causes damage. Before, the only way to identify Alzheimer's was through an autopsy of the brain.

Researchers suspect that plaques and tangles growing in the brain are destroying nerve cells and pathways in some forms of the disease. Researchers hope ultimately to treat the disease by targeting risk factors, such as the plaques, with drugs. Petersen compares the process to preventing or slowing heart disease.

"By knowing the risk factors for heart disease, doctors can treat those risk factors and prevent the heart attack," he says. The aim is to identify drugs to treat the risk factors for Alzheimer's in the same way statins lower bad cholesterol levels, one of the primary risk factors for heart disease.

The drugs for Alzheimer's only treat the symptoms. Once symptoms appear, it is too late to stop the disease from progressing and killing more brain cells.

Bob Blackwell takes Aricept and Namenda, drugs approved by the Food and Drug Administration to treat two different brain-messaging symptoms at different stages of the disease. Their effect is usually modest.

"They helped enormously, especially in the beginning," Carol says. "It was like getting Bob back for a year."

She hoped the fact that Bob was in good physical health would help. Both she and Bob are slim and fit. "We've done everything right," she says. "We've eaten right, exercised, done all the things they recommend to ward off disease. But it doesn't work (against Alzheimer's). I've seen this disease take down the best and brightest."

A growing list of 'lasts'

She takes Bob to adult day care two days a week, where he does activities with other Alzheimer's patients.

"He didn't like it at first," she says, but she had no other option. She works part-time and could not leave him alone at home. "I tried that once, and he called my daughter and daughter-in-law, and he said he'd been abandoned."

Bob has always been a photography buff, but his illness makes it difficult for him to remember the settings on the camera. He has boxes full of images from trips to St. Petersburg, Russia, and to a family cottage in Michigan.

"The neurologist told me we couldn't travel anymore because of how his disease has progressed," Carol says. "It's too confusing for him."

In a blog she keeps for USA TODAY, she has been writing about "the season of lasts" — listing things Bob has done for the last time. He has been a lifelong fan of University of Georgia football, for instance, but following the games last fall was too challenging. Exhibiting his photos in shows also is too taxing.

The past couple of weeks, Bob has been getting up around 5:30 a.m. and wandering around the house.

"He was fully dressed the first time, and I'm surprised I didn't hear him," Carol says. "He doesn't try to go outside because he likes to be in the house and hates the cold, but I'm going to have to take precautions and turn on the house alarm."

She says Bob is frustrated, sometimes asking her why he can't get a job.

She shows a visitor photos on the family room wall of a trip Bob took on Air Force II with then-Vice President George H.W. Bush to the former Soviet Union. Bob smiles, raises a finger and points at himself in the photo sitting across from Bush.

He does not remember the vice president's name.

The Path of Least Resistance

How Bacteria Sneak Into Your Blood Through Your Mouth

The inside of the human body is a bacteria-free zone. Bacteria are certainly within you, but they exist only in areas that have a direct channel to the outside world, such as the mouth, intestines and the surface of the skin. These areas are well protected by a layer of cells (epithilial cells) which form a protective barrier to keep away the nasties of the outside world. That’s why there are healthy stomach bacteria, but no healthy liver bacteria. From a certain point of view your lungs and digestive tract still are the outside world, which is why bacteria can get in and live there, sometimes perfectly happily without causing any trouble at all.

Major problems start to happen, however, once bacteria get through that epithelial barrier and into the tissues of your body. Which is why the first bacteria of the new year is the oral bacteria Fusobacterium nucleatum, which has a trick to open up little doors in blood vessels. These aren’t massive holes, not big enough to cause bleeding but large enough to let it and other bacteria into the bloodstream.

The bacteria in all their blobby glory! These are actually the related Fusobacterium novum. Image taken from the CDC Public Health Image Library (link below).

This is a big issue, because once the bacteria get into the blood-stream they can travel around anywhere within the body. It’s not  just the blood-vessels in the mouth that the F. nucleatum can get into, it can also bypass a lot of other cellular barriers such as the blood-brain barrier that keeps bacteria out of your brain, and the placental barrier that guards the passage of substances between a pregnant mother and the foetus.

The bacteria works by releasing a chemical which is picked up by the cells that make up blood vessels (endothelial cells) and causes the cells to become more permeable. More technically the bacterial chemical (a FadA adhesin) binds to a protein on the cells (vascular endothelial cadherin) that helps to keep the endothelial cells joined together and causes it to migrate away from the cell-cell junction. This opens the junctions up slightly and makes the whole vessel more permeable.

Endothelial cells that form a lining around the blood-vessels. Cell-cell junction in blue and nucleus in red. Pic (c) me.

FadA (the bacterial chemical) is an interesting little molecule, and while it’s highly conserved in F. nucleatum and related oral bacterial species, it has been lost in many closely related species which do not populate the human mouth. This is a protein with one specific purpose – to open blood vessels – and where that function is not needed the bacteria has no need for the protein. When it’s first made by the cell it exists in a form called pre-FabA which anchors to the bacterial membrane with the soluble part (the actual FabA) on the outside of the bacteria ready to be deployed.

To test whether the FabA and the cell cadherin could bind, the researchers carried out a whole range of different binding tests (more information in the  reference below). First, they did a yeast-two-hybrid screen, a sort of sciency quick and dirty method to see if two proteins can bind each other. Then they took both proteins out of the cell to see if they could bind separately, by sticking one protein to a column and seeing if it could ‘catch’ the other as it was washed through. Finally they put both proteins back in the cell with coloured markers attached to see if the coloured markers appeared in the same places. All of these results, along with the actual structures of the two proteins, suggest very strongly that they bind.

One of the most interesting tests they did was to see whether the F. nucleatum was just opening the floodgates for itself, or whether other bacteria were sneaking in at the same time. They did this by making little wells with endothelial tissue between them. Sure enough, those cultures containing E. coli along with F. nucleatum showed that both bacteria could travel through the endothelium together, whereas in cultures containing only E. coli the bacteria remained on one side of the membrane.

New Study: Vegetarians Have More Tooth Decay

Research Suggests Vegans Are More Likely to Develop Cavities

A study published this week in the peer reviewed medical journal, The American Journal of Clinical Nutrition, finds that vegetarians are much more likely to suffer from tooth decay, lower (more acidic) salivary pH levels, and lower stimulated saliva flow than control subjects that were matched by sex and age.

The study confirms what Dr. Weston A. Price DDS in his book Nutrition and Physical Degeneration, discovered on his 10 year journey around the world studying isolated, traditional societies still untouched by what he termed “the displacing foods of modern commerce.”

Dr. Price found that indigenous vegetarian cultures suffered from tooth decay at a higher rate than either the omnivore or the almost completely carnivorous cultures he studied.

The published study concluded that eating a vegetarian diet does not in any way impart a dental health advantage over non-vegetarians.

Tooth decay is an indication of lowered immune function and a higher susceptibility to degenerative disease in general.  Ever heard of the term “don’t look a gift horse in the mouth”?  This refers to the well known historical practice of examining a horse’s teeth and gums to assess overall health elsewhere in the body.  People can similarly assess their level of general health and whether it is improving or declining by observing the health of their teeth and gums.

Rami Nagel, author of the book Cure Tooth Decay, states that the dentinal-fluid transport mechanism is how the body controls the rate of tooth decay including whether or not it occurs at all.  When tooth decay is present, Mr. Nagel says this is a sign that blood sugar levels are askew and that certain critical nutrients such as the fat soluble activators A, D, and K2 are lacking in the diet.

Vegetarian diets are typically much higher in grains and sugars (from fruit) than non-vegetarians, and when the body senses too much sugar at one time, this can initiate demineralization of the teeth.  Ever noticed how your teeth can get a bit sensitive for a period of time after a very sugary dessert or a day that included too many grain based foods and treats?

If you are vegetarian and have noted a problem with dental decay, incorporating grassfed meats, raw grassfed dairy, wild seafood, and high vitamin cod liver oil into your diet will introduce the critical nutrients that are necessary to reverse this condition and prevent further problems.  Moreover, whenever sweet foods such as fruit are consumed, they should always be eaten in the presence of a healthy fat like cream to maintain stable blood sugar and not disrupt the body’s ability to transport minerals.

Source:  The American Journal of Clinical Nutrition, 27 Dec 2011, 712-738

Chocolate Lovers Find New Reason to Embrace Home Care

New toothpaste substitutes cocoa extract for fluoride

A New Orleans start-up has developed a toothpaste that uses a naturally occurring compound found in cocoa instead of fluoride to help strengthen teeth.

Theodent relies on Rennou, a proprietary blend of a cocoa extract and other minerals that work together to strengthen teeth. The extract is a white crystalline powder with a chemical makeup similar to caffeine, according to Arman Sadeghpour, PhD, Theodent president and CEO.

Theodent Classic and Theodent 300 toothpaste, both

of which use a cocoa extract in place of fluoride. 

Theodent Classic ($9.99) hit store shelves at Whole Foods Markets last week. Theodent 300, an extra-strength and luxury version ($99.99) for supersensitive teeth, will be marketed to select cosmetic dentists and medical professionals, according to the company."Theodent is more effective at strengthening enamel than fluoride," he said in an interview with DrBicuspid.com."More and more people are shying away from fluoride due to concerns about toxicity."

Rennou was discovered by Tetsuo Nakamoto DDS, PhD, chief scientific officer and chairman of the board at Theodent, while researching the effect of caffeine on teeth at the Louisiana State University (LSU) School of Dentistry. Dr. Nakamoto collaborated with two experts in analytical geology from the University of New Orleans, and together they discovered Rennou's effects on teeth and enamel.

How it works

Enamel is made up hundreds of thousands of calcium and phosphorus unit crystals that form the mineral component of enamel, hydroxyapatite. Through a series of laboratory tests, Dr. Nakamoto's team identified that Rennou increases the size of the surface unit crystals of enamel by four times. Larger unit crystals make teeth less susceptible to bacterial acid demineralization.

Sadeghpour joined this scientific team and completed his doctoral thesis at Tulane University by comparing Rennou head to head with fluoride and confirmed that it was more effective than fluoride at strengthening teeth.

He used a neural network analysis model to study the effect of Rennou versus fluoride on the enamel surface of human teeth. Two experiments were performed for the study: the first examining enamel surface microhardness, followed by an acid dissolution study.

Through this research, Sadeghpour found that human teeth treated with varying doses of Rennou were generally stronger than those treated with fluoride and also more resilient to bacterial acid demineralization. His research became the foundation of taking this discovery and turning it into a product.

After Sadeghpour finished his doctoral thesis, Tulane University did a small press release on the findings. He then received a call from Clifton Carey, PhD, director of independent research at the ADA, who then independently studied Rennou.

In his research, Carey took initial radiographs of teeth before placing them in distilled water, fluoride, or Rennou for two minutes, Sadeghpour explained. He then subjected these teeth to an acid attack (1% citric acid at a pH of 3.9) for 10 minutes and measured how many microns of enamel were lost.

Carey found that the tooth in distilled water lost 8.88 microns, the one in fluoride lost 5.47 microns, and Rennou beat both fluoride and control group with 3.12 microns of erosion.

That in itself was interesting, according to Sadeghpour. But he also was intrigued that the concentration of Rennou used in the study was very small compared with the concentration of fluoride.

30 years of research

Rennou has also been studied by researchers from Tulane University, the University of New Orleans, Marmara University Dental School in Turkey, the University of Groningen's Faculty of Medical Sciences Department of Dentistry and Dental Hygiene in the Netherlands, the University of Texas at San Antonio, and the ADA.

"Theodent is the culmination of 30 years of research, and its effectiveness has been verified by two issued U.S. patents and a third worldwide patent pending," Sadeghpour said.

Theodent has a minty taste, is nontoxic, and safe for adults and children of all ages, according to the company. The developers hope to expand the product line to include dental floss, mouthwash, and a chocolate-flavored, sugar-free toothpaste for children.

It is now commercially available in 20 U.S. states -- Arizona, Arkansas, California, Connecticut, Hawaii, Illinois, Indiana, Louisiana, Michigan, Minnesota, Missouri, Nebraska, Nevada, New Jersey, New York, Oklahoma, Oregon, Texas, Washington, and Wisconsin -- as well as in Canada in Ontario and British Columbia.

At a January 4 press conference announcing Theodent, Henry Gremillion, DDS, dean of the dental school at LSU, called the new toothpaste a "major step forward in oral health maintenance and prevention."

The Fight Against Cavities: Is Fluoride Winning the Battle?

New study reveals how bacteria fight fluoride

Researchers from Yale University have uncovered the molecular "tricks" used by bacteria to fight the effects of fluoride (Science, December 22, 2011).

The researchers found that sections of RNA messages called riboswitches -- which control the expression of genes -- detect the buildup of fluoride and activate the defenses of bacteria, including those that contribute to tooth decay.

"These riboswitches are detectors made specifically to see fluoride," stated senior study author Ronald Breaker, PhD, chair of the department of molecular, cellular, and developmental biology, in a press release.

Fluoride in over-the-counter and prescription toothpastes is widely credited with the large reduction in dental cavities, which is largely caused by fluoride bonding to the enamel of teeth. However, it has been known for many decades that fluoride at high concentrations also is toxic to bacteria, causing some researchers to propose that this antibacterial activity also may help prevent cavities.

The riboswitches work to counteract fluoride's effect on bacteria.

"If fluoride builds up to toxic levels in the cell, a fluoride riboswitch grabs the fluoride and then turns on genes that can overcome its effects," Breaker said.  "Since both fluoride and some RNA sensor molecules are negatively charged, they should not be able to bind," he noted.

"We were stunned when we uncovered fluoride-sensing riboswitches" Breaker said. "Scientists would argue that RNA is the worst molecule to use as a sensor for fluoride, and yet we have found more than 2,000 of these strange RNAs in many organisms."

The new findings from Yale only reveal how microbes overcome fluoride toxicity. The means by which humans contend with high fluoride levels remains unknown, Breaker noted. The use of fluoride has had clear benefits for dental health and that these new findings do not indicate that fluoride is unsafe as currently used, he added.

New Drug-free Solution to Burning Mouth Syndrome

Mechanical salivary stimulation eases symptoms of BMS.

Chewing on a piece of silicone can ease the symptoms of burning mouth syndrome, Brazilian researchers say.

This rare chronic condition is characterized by a burning sensation or other dysesthesia in otherwise normal appearing oral mucosa. Multiple parts of the mouth can be affected, but the tongue is the most common site (glossopyrosis). Burning mouth syndrome is most often seen in postmenopausal women. Prevalence estimates have ranged from 0.7 to 15.0%, with the wide variations attributed to differences in diagnostic criteria.

As reported online November 15 in Headache, Dr. Fabricio T. A. de Souza from Universidade Federal de Minas Gerais, Belo Horizonte, and colleagues had 26 patients spend 10 minutes, three times a day, chewing on a soft three-dimensional piece of silicone. Patients with dentures were told to remove them during the treatments.

After 90 days of this regimen, patients reported significant decreases in the frequency of symptoms, the number of burning sites, and burning sensations as quantified with a visual analog score.  Three-quarters of patients with taste disturbances at baseline reported improvement with treatment, and 13 of 17 women with subjective oral dryness also reported improvement.  There were no changes in resting or stimulated salivary flows, nor in the qualitative features of the saliva (viscosity, turbidity, and staining).  There was, however, "…a significant decrease in salivary levels of total protein and an increase in TNF-alpha, which may account for the clinical effectiveness of therapy," according to the authors.

Their paper did not explain how an increase in TNF-alpha could account for the effect of treatment, and the authors have not responded to a request for comment.  The researchers did acknowledge that without a control group, it's impossible to know whether the results were influenced by a placebo or Hawthorne effect (i.e., the tendency of some people to do better just because they're participating in an experiment).