Poor Dental Health May Lead to Alzheimer’s

(Journal of Alzheimer’s Disease) People with poor oral hygiene or gum disease may be at a greater risk of developing Alzheimer’s disease, a new study led by The University of Central Lancashire (UCLan) School of Medicine and Dentistry suggests.

The research, which has received international collaboration, and led by Professor Stjohn Crean and Dr Sim Singhrao from UCLan, examined brain samples donated by ten patients without dementia and ten patients suffering from dementia. The research demonstrated the presence of products from Porphyromonas gingivalis in brains from patients suffering from dementia.

This bacterium is commonly associated with chronic periodontal (gum) disease. These bacteria enter the bloodstream through daily activities such as eating, chewing, tooth brushing but especially following invasive dental treatment, and from there, potentially enter the brain on a regular basis. The researchers propose that every time they reach the brain, the bacteria may trigger immune system responses by already primed brains cells, causing them to release more chemicals that kill neurons. This could be one mechanism that leads to changes in the brain, which is typical of Alzheimer’s disease, and could be responsible for causing symptoms such as confusion and deteriorating memory.

The research benefited from donated brain samples, provided by Brains for Dementia Research, a brain donation scheme supported by Alzheimer’s Research UK and Alzheimer’s Society. Finding P. gingivalis in the brains from dementia sufferers compared to those without dementia is significant as its presence in Alzheimer’s diseased brains has not been documented previously and at the same time adds to a growing body of evidence that suggests an association between poor oral health and dementia.

These published research findings from human brain specimens are further supported by recent (as yet unpublished) research from the same group, on periodontal disease, using animal models, which has been carried out in collaboration with the University of Florida. This animal work has confirmed that P. gingivalis in the mouth finds its way to the brain once the periodontal disease becomes established.

Professor Stjohn Crean, Dean, School of Medicine & Dentistry said:

“Whereas previous studies have indicated a link between dementia and other bacteria and viruses such as the Herpes simplex virus type I, this new research indicates a possible association between gum disease and individuals who may be susceptible to developing Alzheimer’s disease, if exposed to the appropriate trigger!

Research currently underway at UCLan is playing an active role in exploring this link, but it remains to be proven whether poor dental hygiene can lead to dementia in healthy people, which obviously could have significant implications for the population as a whole. It is also likely that these bacteria could make the existing disease condition worse.”

Dr. Sim K. Singhrao, Senior Research Fellow at UCLan said: “We are working on the theory that when the brain is repeatedly exposed to bacteria and/or their debris from our gums, subsequent immune responses may lead to nerve cell death and possibly memory loss. Thus, continued visits to dental hygiene professionals throughout one’s life may be more important than currently envisaged with inferences for health outside of the mouth only.

To help us prove our hypothesis we are hoping to use the Brains for Dementia Research tissue resource to examine brain tissue from people with both intact and compromised memory who have relevant dental records. The future of the research aims to discover if P. gingivalis can be used as a marker, via a simple blood test, to predict the development of Alzheimer disease in at risk patients.

The American Dental Hygienists’ Association (ADHA) recommend that we brush our teeth for 2 minutes, twice a day. The ADHA guidelines also stress the importance of flossing daily and rinsing with mouthwash. Read about the recommendations here.

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University Study Links Sugary Beverages to Memory Problems

(University of Southern California) Consumption of high-fructose corn syrup leads to brain inflammation in adolescent rats. Studying rats as model subjects, scientists found that adolescents were at an increased risk of suffering negative health effects from sugar-sweetened beverage consumption.

Adolescent rats that freely consumed large quantities of liquid solutions containing sugar or high-fructose corn syrup (HFCS) in concentrations comparable to popular sugar-sweetened beverages experienced memory problems and brain inflammation, and became pre-diabetic, according to a new study from USC. Neither adult rats fed the sugary drinks nor adolescent rats that did not consume sugar had the same issues.

“The brain is especially vulnerable to dietary influences during critical periods of development, like adolescence,” said Scott Kanoski, corresponding author of the study and assistant professor at the USC Dornsife College of Letters, Arts and Sciences.

Kanoski collaborated with USC’s Ted Hsu, Vaibhav Konanur, Lilly Taing, Ryan Usui, Brandon Kayser and Michael Goran. The study, which tested a total of 76 rats, was published online by the journal Hippocampus on Sept. 23.

Soft drinks, sodas, sugar

About 35 to 40 percent of the rats’ caloric intake was from sugar or HFCS. For comparison, added sugars make up about 17 percent of the total caloric intake of teens in the United States on average, according to the U.S. Centers for Disease Control and Prevention.

The rats were then tested in mazes that probe their spatial memory ability. Adolescent rats that had consumed the sugary beverages, particularly HFCS, performed worse on the test than any other group, which may be the result of the neuroinflammation detected in the hippocampus, Kanoski said.

The hippocampus is a part of the temporal lobe located deep within the brain that controls memory formation. People with Alzheimer’s and other dementias often suffer damage to the hippocampus.

“Consuming a diet high in added sugars not only can lead to weight gain and metabolic disturbances, but can also negatively impact our neural functioning and cognitive ability,” said Kanoski, whose team next plans to see how different monosaccharides (simple sugars) and HFCS affect the brain.

The research was funded by USC institutional support.

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What Do People Believe About Alzheimer’s Disease?

(EndAlzNow.org) Alzheimer’s is a devastating, debilitating and incurable disease of the brain. Its symptoms develop slowly, although researchers now believe that the actual neurological damage begins years or even decades before the first memory and thinking problems occur. Those symptoms are progressive, ultimately robbing the individual of mental and physical function.

Did You Know?

  • Alzheimer’s is the most common form of dementia. It is not a normal part of aging, although the greatest known risk factor is increasing age.
  • Approximately 5.2 million Americans are living with Alzheimer’s today, with one new case diagnosed every 68 seconds.
  • One in nine Americans over age 65—and nearly one in three Americans over age 85—is currently diagnosed with Alzheimer’s.
  • The prevalence of Alzheimer’s is projected to increase sharply in coming decades because of the nation’s aging population. By 2050, that number could nearly triple to a projected 13.8 million.
  • Early-onset Alzheimer’s, which involves about 3 percent of all Alzheimer’s diagnoses, is identified by symptoms that begin before age 65.
  • Alzheimer’s is the sixth-leading cause of death in the U.S. and the only cause of death among the top 10 that cannot be prevented, slowed or cured.

What Do People Believe About Alzheimer’s Disease?

  • Three-quarters of U.S. adults are interested in participating in general medical research studies, while more than half are interested in taking part in clinical trials.
  • One in 10 adults is responsible for providing or arranging care for a relative or friend with the disease.
  • More than half of U.S. adults believe that not enough is being done to fight Alzheimer’s disease.
  • More than four in 10 U.S. adults are very concerned about Alzheimer’s, either for themselves or a loved one.
  • Three-quarters of U.S. adults believe Alzheimer’s will become a very significant health problem in this country over the next 10 years.
  • Nearly six in 10 U.S. adults consider the development of treatments and ultimately a cure for Alzheimer’s among the nation’s most important health issues.

For more information about Alzheimer’s disease, please visit the links below:

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Getting to the Heart of It: Healthy Heart and Healthy Brain

(Alzheimer’s Prevention Registry) If you’re heading to the fitness center for regular workouts, shedding those extra pounds or kicking a tobacco habit with heart health in mind, here’s good news: you also may be lowering your risk for dementia.

“In other words, what’s good for a person’s heart is also good for the brain,” said Gabrielle Strobel, executive editor of Alzforum.

This is a key message of the World Alzheimer Report 2014, which is published by Alzheimer’s Disease International (ADI) – a worldwide organization of more than 80 Alzheimer’s associations – and international health insurance provider Bupa.

This year’s report, Dementia and Risk Reduction: An analysis of protective and modifiable factors highlights how people can reduce their risk of developing Alzheimer’s disease or other dementias by:

  • Giving up cigarettes
  • Controlling blood pressure to prevent hypertension
  • Managing blood sugar to avoid diabetes
  • Maintaining a healthy weight
  • Exercising regularly

“A healthy lifestyle protects your brain and lowers your risk of developing dementia later in life,” Strobel said. “This is a hopeful, empowering message, as these are things everyone can do. It’s never too early to adopt this healthy lifestyle.”

Lifestyles and life stages came together in several of the report’s key findings. The report’s authors, led by Professor Martin Prince of King’s College London, noted that the risk of developing dementia increases with:

  • Lower education early in life;
  • High blood pressure in midlife; and
  • Diabetes across an entire life.

ADI’s report echoes other research that suggests improving heart health, consuming a sensible diet and maintaining an active lifestyle helps ward off dementia. Even so, according to a previous Bupa survey, most people are unaware of these important healthy lifestyle connections.

What does ADI recommend to remedy this? If the organization has its way, future anti-tobacco and public health awareness campaigns will encourage people of all ages to adopt healthy habits for better brain health.

“While this is true in general and for groups of people,” said Strobel, “one can never guarantee that a healthy lifestyle will protect any given person, just like smoking is a risk factor for lung cancer but some non-smokers get it, too.”

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Stress and Its Influence on Alzheimer’s Disease

(UC Irvine Mind) It’s become almost impossible to escape stress in our 21st century American life. Ongoing economic insecurity, a constant sense of time urgency fueled by instantaneous communication, and the multiple competing demands of family and work life, including caregiving, leave Americans with little opportunity to take a breather.

stick_figure_headache_1600_wht-136x300In a nationwide survey of 1,226 Americans released by the American Psychological Association in January 2012, 44 percent reported experiencing increased stress over the past five years, and 22 percent recounted suffering extreme stress in 2011. While our bodies are equipped to manage real or perceived threat and then return to a normal state, the constant stress associated with meeting the demands of modern life can impair this ability, damaging both our bodies and our brains.

When a stressful event occurs, our autonomic nervous system automatically initiates a “fight or flight” response during which the adrenal glands produce a rush of adrenaline and, if the crisis is severe or prolonged, cortisol, a long-acting stress hormone. A series of physiological changes (e.g., increase in blood pressure, heart rate, and breathing) prepare the body for an assault. Initially, the surge in stress hormones also sharpens memory and senses, leading to a hyper-alert state.

Once the crisis is over, our parasympathetic nervous system induces a relaxation response in which the body’s systems gradually resume normal functioning – a process that can take hours, days, and sometimes weeks. Called allostasis, the entire stress-relaxation cycle ensures harmonious functioning of the mind and body during and after a crisis.

While some stress can “keep you on your toes,” too much can damage your cardiovascular system, gastrointestinal tract, brain, and more. When stress is repetitive or unremitting, the body’s systems suffer wear and tear from repeated allostasis and the process can go haywire.

Inefficiency in the stress response (e.g., inability to turn the response on or off) caused by metabolic wear and tear is known as “allostatic loading.” Over time, allostatic loading can have profoundly negative effects on the body, leading to conditions such as metabolic syndrome, hypertension, and ulcers as well as speeding up cellular aging.

Stress is equally deleterious for the brain. Multiple studies suggest that too much stress, sometimes referred to as distress, increases risk for cognitive decline and Alzheimer’s disease. While small doses of cortisol over short periods can boost learning and memory, excessive or prolonged elevations can do just the opposite. Whether caused by an external stressor or internal tension, chronic stress harms the brain in multiple ways.

First, it impairs communication among brain cells or neurons. Dendrites – branch-like extensions from neurons that receive impulses from neighboring cells – shrivel in the presence of excessive cortisol. As well, neurotransmitters, chemicals responsible for transmitting messages from one brain cell to another, malfunction.

stick_figure_world_shoulder_400_wht-300x300Secondly, chronic stress may slow the production of new neurons to replace injured or dying cells (i.e., neurogenesis) in the hippocampus, resulting in atrophy of this critical structure for learning and memory. As demonstrated by Dr. Sonia Lupien at McGill University in Montreal, older adults with continuously high levels of cortisol perform worse on memory tests than those with low to moderate levels of the stress hormone and, on average, have a 14% smaller hippocampus.

As the hippocampus degenerates, it becomes unable to fulfill its function of signaling the adrenal gland to stop secreting cortisol when a crisis is over. A downward spiral ensues as cortisol levels continue to climb, intensifying damage to the hippocampus, and further weakening its ability to shut down cortisol production.

Thirdly, in a study conducted at UCI MIND, Dr. Kim Green and his colleagues found that stress hormones accelerated the development of Alzheimer’s in mice that had been genetically engineered to develop disease as they age. After just seven days of injecting young mice that were not yet old enough to show Alzheimer’s pathology, the researchers discovered elevated levels of the two abnormal proteins that underlie the disease.

Both the amyloid β-peptide that clumps into senile plaques and the abnormal form of tau which twists into neurofibrillary tangles were elevated. While previous researchers had shown a connection between stress and risk for cognitive decline, Dr. Green and his colleagues helped to elucidate the “why” behind the connections.

Stress, unlike other risk factors for Alzheimer’s disease (e.g., age), is modifiable. Much of the damage that stress can cause to the body and the brain can be avoided or even reversed by learning to better manage stress and engaging in stress-reducing activities.

 Protect Your Brain from Stress

  • Learn a relaxation response technique such as meditation or progressive muscle relaxation.
  • Build optimism by practicing cognitive skills to counteract automatic negative thoughts that lead to stress and depression.
  • As much as possible, take charge of your life and enjoy it. Feeling that you can influence your daily life can reduce stress.
  • Exercise to reduce stress and promote growth of new neurons in the brain.
  • Eat and sleep well. A nourishing low-fat diet and at least seven hours of sleep a night can help replenish your physical, mental, and emotional resources.
  • Build your social support network. Lack of social support increases vulnerability to the damaging effects of stress.
  • Give to others. Altruistic, unselfish behavior can help you develop a more positive attitude toward life.

 

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Overcompensation — It Could Work for the Brain

(AlzForum) Some people seem to cope better than others with having amyloid plaques in their brains. According to a study in the September 14 Nature Neuroscience, they maintain cognitive prowess by kicking neural networks into overdrive. Such hyperactivity had been observed before, but researchers were unsure if it was beneficial. The new study, led by William Jagust at the University of California, Berkeley, suggests that it is. In cognitively normal people harboring amyloid, those with greater activation remembered in greater detail.

“This is incredibly intriguing,” said John Cirrito of Washington University, who was not involved in the study. “One of the most remarkable things about the brain is that it adapts and compensates in response to injury.”

Cognitively normal people whose brains are riddled with amyloid plaques have baffled AD researchers, especially those who subscribe to the hypothesis that amyloid causes the disease. Some neural networks are hyperactive when otherwise healthy people with brain Aβ perform learning and memory tasks, while other networks fail to switch off when they should (see Aug 2009 news storyMormino et al., 2011Dickerson et al., 2004; and Apr 2014 news story). Researchers have wondered whether these abnormal neural activation patterns reflect a dedicated compensatory mechanism, a harbinger of dementia, or both.

compensation_2Compensation Through Activation. As a memory is made, the brain tones down activity in some regions (blue), while ramping it up in others (orange). People who have amyloid in their brain seem to compensate for it by activating those brain regions even more. [Image courtesy of Elman et al., Nature Neuroscience 2014.]

To address the first possibility, co-first authors Jeremy Elman and Hwamee Oh tested whether rises in neural activity in people harboring amyloid plaques correlated with better memory. They studied 22 healthy young participants and 49 cognitively normal people over age 65. The researchers split the older participants into two groups—amyloid positive and amyloid negative—based on PiB retention.

All were presented with a series of complex images of everyday scenes, while their neural activity was recorded via fMRI. Fifteen minutes later, the researchers showed the participants a simple true-or-false question about each of the images to assess the extent of their “gist memory.” If a person remembered the gist of the image, for example, whether it showed a boy on a skateboard, then the researchers asked six more detailed questions about the image to measure the richness of the memory, e.g., was he wearing a blue shirt?

On average, the three groups performed equally well on the memory tests. The researchers then averaged the participants’ memory scores and correlated them with the patterns of neural activity observed while the memories were encoded.

Overall, the investigators found that when people were viewing a picture they later remembered, the regions of the brain involved in memory—called the task-positive network, or TPN—lit up, whereas the default mode network (DMN), which normally fires while the brain is at rest, was shut down (see image above). Compared with older people without amyloid, people with amyloid displayed higher levels of neural activity in the TPN and lower levels of DMN deactivation when looking at images that they later recalled.

The researchers took advantage of the memory detail data to determine whether heightened neural activity in people with amyloid deposition gave them an edge. They correlated the number of details each participant recalled with their neural activity when the memory was made. For older people devoid of amyloid, neural activity in the TPN switched on, but did not ramp up linearly with more details being recalled. Rather, the DMN progressively deactivated as the details improved in this group. In contrast, in both young people and older people with amyloid, TPN activation, but not deactivation of the DMN, correlated with greater details remembered.

“People with amyloid recalled more details as their brain activity went up, so that seems to tell us that this ramping up of activity serves a function,” Jagust told Alzforum. “It’s not some kind of random noise, and in fact it seems to be helping people,” he said.

Older people without amyloid may rely more on the deactivation of the DMN to focus, as opposed to the increases of TPN activity seen in people with amyloid, he speculated.

Gael Chetelat of the French Institute of Health and Medical Research in Paris agreed that this was one possible explanation.

“While in normal aging, difficulties may arise from an inability to focus attention resources on the task, elderly with amyloid deposits specifically increase their activity in task-related regions to maintain their performance,” she wrote in an email to Alzforum.

Interestingly, in people with the highest levels of amyloid, the researchers noticed that the tight coupling between neural activity and detailed recall started to unravel.

“This might be a sign that this compensation wears out,” Jagust suggested, although the researchers will not know this until follow-up studies are done.

Previous studies have reported that neuronal activity triggers the release of amyloid and tau (see May 2011 news story and Feb 2014 news story). This suggests that this compensatory mechanism, though beneficial in the short run, could one day lead to a further spread of pathology, said Willem Huijbers of Harvard University.

“Something might be beneficial for memory performance, but in the long run it could be detrimental to the brain,” he said, “That’s the question you’re left with.”

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Pathway that Contributes to Alzheimer’s Disease Revealed by Research

(Mayo Clinic) Researchers at Jacksonville’s campus of Mayo Clinic have discovered a defect in a key cell-signaling pathway they say contributes to both overproduction of toxic protein in the brains of Alzheimer’s disease patients as well as loss of communication between neurons — both significant contributors to this type of dementia.

140919140738-largeLoss of LRP6 in neurons leads to enhanced buildup of amyloid protein, a pathological hallmark of Alzheimer’s disease.
Credit: Image courtesy of Mayo Clinic

Their study, in the online issue of Neuron, offers the potential that targeting this specific defect with drugs “may rejuvenate or rescue this pathway,” says the study’s lead investigator, Guojun Bu, Ph.D., a neuroscientist at Mayo Clinic, Jacksonville, Fla.

“This defect is likely not the sole contributor to development of Alzheimer’s disease, but our findings suggest it is very important, and could be therapeutically targeted to possibly prevent Alzheimer’s or treat early disease,” he says.

The pathway, Wnt signaling, is known to play a critical role in cell survival, embryonic development and synaptic activity — the electrical and chemical signals necessary for learning and memory. Any imbalance in this pathway (too much or too little activity) leads to disease — the overgrowth of cells in cancer is one example of overactivation of this pathway.

While much research on Wnt has focused on diseases involved in overactive Wnt signaling, Dr. Bu’s team is one of the first to demonstrate the link between suppressed Wnt signaling and Alzheimer’s disease.

“Our finding makes sense, because researchers have long known that patients with cancer are at reduced risk of developing Alzheimer’s disease, and vice versa,” Dr. Bu says. “What wasn’t known is that Wnt signaling was involved in that dichotomy.”

Using a new mouse model, the investigators discovered the key defect that leads to suppressed Wnt signaling in Alzheimer’s. They found that the low-density lipoprotein receptor-related protein 6 (LRP6) is deficient, and that LRP6 regulates both production of amyloid beta, the protein that builds up in the brains of AD patients, and communication between neurons. That means lower than normal levels of LRP6 leads to a toxic buildup of amyloid and impairs the ability of neurons to talk to each other.

Mice without LRP6 had impaired Wnt signaling, cognitive impairment, neuroinflammation and excess amyloid.

The researchers validated their findings by examining postmortem brain tissue from Alzheimer’s patients — they found that LRP6 levels were deficient and Wnt signaling was severely compromised in the human brain they examined.

The good news is that specific inhibitors of this pathway are already being tested for cancer treatment.

“Of course, we don’t want to inhibit Wnt in people with Alzheimer’s or at risk for the disease, but it may be possible to use the science invested in inhibiting Wnt to figure out how to boost activity in the pathway,” Dr. Bu says.

“Identifying small molecule compounds to restore LRP6 and the Wnt pathway, without inducing side effects, may help prevent or treat Alzheimer’s disease,” he says. “This is a really exciting new strategy — a new and fresh approach.”

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World Alzheimer’s Report: Preventing Dementia through Lifestyle Changes

(AlzForum) With predictions of a coming global avalanche of dementia cases, researchers are turning their attention to prevention strategies. Based on current data, at least four lifestyle factors robustly affect dementia risk, according to the World Alzheimer Report 2014, released September 16 by the umbrella group Alzheimer’s Disease International and Bupa, the largest private health insurance company  in the United Kingdom.

Researchers led by Martin Prince at King’s College London analyzed previous studies that examined the effects of developmental, psychological, lifestyle, and cardiovascular factors on dementia risk. They found that diabetes heightened risk by 50 percent, while smoking increased the odds of Alzheimer’s disease by the same amount. Hypertension in midlife pumped up the risk for vascular dementia by 60 percent, while education lowered dementia risk by about 40 percent.

Factors such as depression and obesity also appeared to inflate risk, while physical activity and cognitive stimulation seemed to lower it, but existing data are not strong enough to draw firm conclusions about those factors, the report noted.

The findings belie the report from a 2010 National Institutes of Health State-of-the-Science panel, which concluded that insufficient evidence existed to endorse any health intervention for lowering Alzheimer’s risk (see May 2010 news story; May 2011 news story). The World Alzheimer Report argues that,

“There is persuasive evidence that the dementia risk for populations can be modified through reduction in tobacco use and better control and detection for hypertension and diabetes, as well as cardiovascular risk factors.”

The findings add to a growing body of evidence suggesting that improving heart health and maintaining an active lifestyle and sensible diet wards off dementia (see, e.g., Jul 2014 news story; Apr 2014 news story). Researchers attribute recent drops in dementia incidence in developed countries to higher education levels and better cardiovascular care (see May 2013 news story; Jul 2013 news story; and Jul 2014 news story).

In 2011, researchers at the University of California, San Francisco, estimated that reducing the prevalence of the risk factors listed above could significantly cut dementia cases worldwide (see Jul 2011 news story). Those researchers recently refined their analysis, concluding that a drop of 10 percent in each risk factor would reduce Alzheimer’s prevalence in 2050 by 8 percent worldwide (see Norton et al., 2014).

Despite all the research on this topic, the public remains largely unaware of the impact of lifestyle factors. In a survey conducted by Bupa, only a quarter of respondents knew that obesity and physical inactivity could increase their odds of developing dementia, and just one in six realized that social activity could protect them. Alzheimer’s Disease International recommends greater public outreach.

“Implementing effective public health campaigns may help to reduce the global risk,” director Marc Wortmann, said in a press release.

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