Are your gums saying something about your dementia risk?

Gum disease, especially the kind that is irreversible and causes tooth loss, may be associated with mild cognitive impairment and dementia 20 years later, according to a study published in the July 29, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"We looked at people's dental health over a 20-year period and found that people with the most severe gum disease at the start of our study had about twice the risk for mild cognitive impairment or dementia by the end," said study author Ryan T. Demmer, Ph.D., M.P.H., of the University of Minnesota School of Public Health in Minneapolis. "However, the good news was that people with minimal tooth loss and mild gum disease were no more likely to develop thinking problems or dementia than people with no dental problems."

The study involved 8,275 people with an average age of 63 who did not have dementia at the start of the study. The participants were assessed for mild cognitive impairment and dementia. Participants received a full periodontal exam that included measuring gum probing depth, amount of bleeding and recession.

Then participants were put into groups based on the severity and extent of their gum disease and number of lost teeth, with implants counting as lost teeth. At the start of the study, 22% had no gum disease, 12% had mild gum disease, 12% had severe gum inflammation, 8% had some tooth loss, 12% had disease in their molars, 11% had severe tooth loss, 6% had severe gum disease, and 20% had no teeth at all.

A total of 4,559 people was assessed at the end of the study, when they had been followed for an average of 18 years.

Overall, 1,569 people developed dementia during the study, or 19%. This was the equivalent of 11.8 cases per every 1,000 person-years. The study found that of the people who had healthy gums and all their teeth at the start of the study, 264 out of 1,826, or 14%, developed dementia by the end of the study. For those with mild gum disease, 623 out of 3,470, or 18%, developed dementia. For participants with severe gum disease, 306 out of 1,368, or 22%, developed dementia. And 376 out of 1,611, or 23%, developed dementia in the group that had no teeth. This was equal to a rate of 16.9 cases per 1,000 person-years.

When looking at both mild cognitive impairment and dementia, the group with no teeth had about twice the risk compared to participants with healthy gums and all their teeth. People with intermediate or severe gum disease, but who still had some teeth, had a 20% greater risk of developing mild cognitive impairment or dementia compared to the healthy group. These risks were after researchers accounted for other factors that could affect dementia risk, such as diabetes, high cholesterol and smoking.

"Good dental hygiene is a proven way to keep healthy teeth and gums throughout your lifetime. Our study does not prove that an unhealthy mouth causes dementia and only shows an association. Further study is needed to demonstrate the link between microbes in your mouth and dementia, and to understand if treatment for gum disease can prevent dementia," Demmer said.

A limitation of the study is the fact that initial gum examinations were made when the participants had an average age of 63, and it is possible that cognitive decline might have been begun before the start of gum disease and tooth loss.

Atomic imaging finds root of tooth decay

A collaboration between researchers from Cornell University, Northwestern University and University of Virginia combined complementary imaging techniques to explore the atomic structure of human enamel, exposing tiny chemical flaws in the fundamental building blocks of our teeth. The findings could help scientists prevent or possibly reverse tooth decay.

The team's paper, "Chemical Gradients in Human Enamel Crystallites," published July 1 in Nature. Cornell's contribution was led by Lena Kourkoutis, associate professor in applied and engineering physics. Derk Joester, professor of materials science and engineering at Northwestern, directed the research.

The paper's co-lead authors are Northwestern doctoral student Karen DeRocher and postdoctoral researcher Paul Smeets.

Thanks to its high mineral count, tooth enamel is a sturdy substance that can withstand the rigors of chewing, although excessive acid in the mouth can make it vulnerable to decay. While scientists have previously peeked into the crystallites that compose enamel, nanoscale images of its structure and chemical composition have been harder to come by. In one method, scanning transmission electron microscopy, or STEM, a beam of electrons is shot through a sample. But that process has its limits.

"Enamel is mechanically a very, very strong material, but when you put it in the electron microscope, it's very sensitive to the electron beam," Kourkoutis said. "So compared to the crystalline materials that you find in electronics, for example, you can only put a fraction of the number of electrons into an enamel crystal. Normally, pushing down to the atomic scale means you have to put more electrons into the material. But if it damages the material before you get the information out, then you're lost."

In recent years, Joester's Northwestern group has imaged sensitive biological materials with atom probe tomography, a process that essentially strips atoms off a sample's surface one at a time and reconstructs the structure of the material.

At the same time, Cornell researchers at PARADIM (Platform for the Accelerated Realization, Analysis and Discovery of Interface Materials), a National Science Foundation-supported user facility, have advanced a form of low-temperature electron microscopy that can image the atomic structure of radiation-sensitive samples. The technique can also safely map a sample's chemical composition by measuring how much energy is lost when the electrons interact with the atoms.

"When you operate at low temperature, the material becomes more robust against electron beam damage," said Kourkoutis, who directs PARADIM's electron microscopy facility. "We are now working at the intersection between the developments in the physical sciences which have pushed electron microscopy to the atomic scale and the developments in the life sciences in the cryogenic field."

The two university groups linked up after Smeets, a member of Joester's group, attended PARADIM's summer school on electron microscopy in 2017. There, he learned how PARADIM's cryogenic electron microscopy capabilities could complement Northwestern's human enamel project.

Smeets worked with Kourkoutis' doctoral students Berit Goodge and Michael Zachman, Ph.D. '18, co-authors of the new paper. The group performed cryogenic electron microscopy on enamel samples that were cooled with liquid nitrogen to around 90 kelvins, or minus 298 degrees Fahrenheit.

By combining their complementary techniques, the Cornell and Northwestern researchers were able to image an enamel crystallite and its hydroxylapatite atomic lattice. But all was not crystal clear: The lattice contained dark distortions -- caused by two nanometric layers with magnesium, as well as sodium, fluoride and carbonate ion impurities near the core of the crystal.

Additional modeling confirmed the irregularities are a source of strain in the crystallite. Paradoxically, these irregularities and the enamel's core-shell architecture may also play a role in reinforcing the enamel, making it more resilient.

The researchers say the findings could lead to new treatments for strengthening enamel and combating cavities.

"On the foundation of what we discovered, I believe that atom probe tomography and correlative electron microscopy will also have tremendous impact on our understanding of how enamel forms, and how diseases like molar incisor hypomineralization disrupt this process," Joester said.

And mouths aren't the only beneficiaries of cryogenic electron microscopy. Kourkoutis is also using the process to probe the chemistry in energy systems, such as batteries and fuel cells that contain a mix of soft electrolytes and hard electrode materials.

The research was supported by the National Institutes of Health's National Institute of Dental and Craniofacial Research, the National Science Foundation and the University of Virginia.

Archaeologists use tooth enamel protein to show sex of human remains

A new method for estimating the biological sex of human remains based on reading protein sequences rather than DNA has been used to study an archaeological site in Northern California. The protein-based technique gave superior results to DNA analysis in studying 55 sets of human remains between 300 and 2,300 years old. The work is published July 17 in Scientific Reports.

The method targets amelogenin, a protein found in tooth enamel, said first author Tammy Buonasera, postdoctoral researcher working with Glendon Parker, adjunct associate professor in the Department of Environmental Toxicology at the University of California, Davis. The technique was developed in Parker's laboratory.

Buonasera, Parker, Jelmer Eerkens, professor of anthropology, and colleagues compared three methods for sex determination: the new proteomic method; DNA analysis; and osteology, or analysis of the size, shape and composition of the bones themselves. They applied these methods to remains from two ancestral Ohlone villages near Sunol, California. The site is being excavated by the Far West Anthropological Research Group of Davis in collaboration with the Muwekma Ohlone tribe.

Amelogenin is a protein found in tooth enamel, the hardest and most durable substance in the human body. The gene for amelogenin happens to be located on both the X and Y sex chromosomes, and the amelogenin-Y protein is slightly different from amelogenin-X.

The method works by retrieving a tiny amount of protein from a tooth. All proteins are made up of a chain of amino acids, so the protein is analyzed to give the amino acid sequence, which then defines the protein. Each of the 20 naturally occurring amino acids is specified by a three-letter code in DNA, so it is possible to work backward from the amino acid sequence and figure out the likely DNA code.

Superior to existing methods

The researchers were able to determine the sex of all of the remains using the new protein method and all but five using DNA methods. Results from osteology and proteomics agreed in almost all cases, although examining bones themselves was only effective for about half the skeletons.

The protein method allowed them to estimate sex for children, which is not possible from osteology. It was reliable even when the signal from DNA was weak.

"This is a more sensitive technique for older skeletons where we would expect more DNA degradation," Parker said.

Being able to determine the biological sex of human remains provides a greater window into the persona of each individual. Anthropologists are interested in determining biological sex because sex interacts with health and can have a large impact on how people form an identity and are treated within a society, Eerkens said.

"Almost every human society around the world incorporates sex and gender as a way to classify people, and these can affect your status and who you associate with in society," Eerkens said. While gender and biological sex are not the same thing, they are linked, so the ability to estimate sex gives archaeologists important insight when attempting to understand the cultural aspects of gender, which are not as readily preserved.

For example, in a society based on small villages, people often have to find mates outside their village. Depending on cultural rules, either men or women will leave the village to marry.

Gum disease may raise risk of some cancers

People with history of gum disease appear to have higher risk of developing oesophageal and gastric cancer, suggest researchers

BMJ

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People who have periodontal (gum) disease may have a higher risk of developing some forms of cancer, suggests a letter published in the journal Gut detailing a prospective study.

US researchers found that a history of periodontal disease appeared to be associated with a raised risk of oesophageal (gullet) cancer and gastric (stomach) cancer and this risk was also higher among people who had lost teeth previously.

Previous findings on the relationship of periodontal disease and tooth loss with oesophageal and gastric cancer have been inconsistent.

Therefore, a team of researchers from Harvard T.H. Chan School of Public Health, in Boston, USA, carried out a study of data on patients over decades of follow up.

They examined the association of history of periodontal disease and tooth loss with the risk of oesophageal and gastric cancer in 98,459 women from the Nurses' Health Study (1992-2014) and 49,685 men from the Health Professionals Follow-up Study (1988-2016).

Dental measures, demographics, lifestyle, and diet were assessed using follow-up questionnaires and self-reported cancer diagnosis was confirmed after reviewing medical records.

The results showed that during 22-28 years of follow-up, there were 199 cases of oesophageal cancer and 238 cases of gastric cancer.

A history of periodontal disease was associated with a 43% and 52% increased risk of oesophageal cancer and gastric cancer, respectively.

Compared to people with no tooth loss, the risks of oesophageal and gastric cancer for those who lost two or more teeth were also modestly higher - 42% and 33%, respectively.

In addition, among individuals with a history of periodontal disease, no tooth loss and losing one or more teeth were equally associated with a 59% increased risk of oesophageal cancer compared to those with no history of periodontal disease and no tooth loss.

Similarly, the same group of individuals had 50% and 68% greater risk of gastric cancer, respectively.

The authors point to possible reasons for an association between oral bacteria (oral microbiota) and oesophageal and gastric cancer, with evidence from other studies suggesting that tannerella forsythia and porphyromonas gingivalis - members of the 'red complex' of periodontal pathogens - were associated with the presence or risk of oesophageal cancer.

Another possible reason is that poor oral hygiene and periodontal disease could promote the formation of endogenous nitrosamines known to cause gastric cancer through nitrate-reducing bacteria.

This was an observational study, so no firm conclusions can be drawn about cause and effect, and the researchers cannot rule out the possibility that some of the observed risk may be due to other unmeasured (confounding) factors.

However, they conclude: "Together, these data support the importance of oral microbiome in oesophageal and gastric cancer. Further prospective studies that directly assess oral microbiome are warranted to identify specific oral bacteria responsible for this relationship. The additional findings may serve as readily accessible, non-invasive biomarkers and help identify individuals at high risk for these cancers."

Materials scientists drill down to vulnerabilities involved in human tooth decay

Enamel formation study could lead to new interventions to prevent and treat disease and defects

NORTHWESTERN UNIVERSITY

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VIDEO: A ROTATING VIEW OF THE "WORLD'S TINIEST SANDWICH. " MAGNESIUM IONS (MAGENTA) FORM TWO LAYERS ON EITHER SIDE OF THE ENAMEL CRYSTALLITE'S CORE, JUST 6 BILLIONTHS OF A METER ACROSS. SODIUM... view more 

CREDIT: NORTHWESTERN UNIVERSITY

Northwestern University researchers have cracked one of the secrets of tooth decay. In a new study of human enamel, the materials scientists are the first to identify a small number of impurity atoms that may contribute to the enamel's strength but also make the material more soluble. They also are the first to determine the spatial distribution of the impurities with atomic-scale resolution.

Dental caries -- better known as tooth decay -- is the breakdown of teeth due to bacteria. ("Caries" is Latin for "rottenness.") It is one of the most common chronic diseases and a major public health problem, especially as the average life expectancy of humans increases.

The Northwestern discovery in the building blocks of enamel -- with detail down to the nanoscale -- could lead to a better understanding of human tooth decay as well as genetic conditions that affect enamel formation, which can lead to highly compromised or completely absent enamel.

Enamel, the human tooth's protective outer layer, covers the entire crown. Its hardness comes from its high mineral content.

"Enamel has evolved to be hard and wear-resistant enough to withstand the forces associated with chewing for decades," said Derk Joester, who led the research. "However, enamel has very limited potential to regenerate. Our fundamental research helps us understand how enamel may form, which should aid in the development of new interventions and materials to prevent and treat caries. The knowledge also might help prevent or ameliorate the suffering of patients with congenital enamel defects."

The study will be published on July 1 by the journal Nature.

Joester, the corresponding author, is an associate professor of materials science and engineering in the McCormick School of Engineering. Karen A. DeRocher and Paul J.M. Smeets, a Ph.D. student and a postdoctoral fellow, respectively, in Joester's lab, are co-first authors.

One major obstacle hindering enamel research is its complex structure, with features across multiple length scales. Enamel, which can reach a thickness of several millimeters, is a three-dimensional weave of rods. Each rod, approximately 5 microns wide, is made up of thousands of individual hydroxylapatite crystallites that are very long and thin. The width of a crystallite is on the order of tens of nanometers. These nanoscale crystallites are the fundamental building blocks of enamel.

Perhaps unique to human enamel, the center of the crystallite seems to be more soluble, Joester said, and his team wanted to understand why. The researchers set out to test if the composition of minor enamel constitutents varies in single crystallites.

Using cutting-edge quantitative atomic-scale techniques, the team discovered that human enamel crystallites have a core-shell structure. Each crystallite has a continuous crystal structure with calcium, phosphate and hydroxyl ions arranged periodically (the shell). However, at the crystallite's center, a greater number of these ions is replaced with magnesium, sodium, carbonate and fluoride (the core). Within the core, two magnesium-rich layers flank a mix of sodium, fluoride and carbonate ions.

"Surprisingly, the magnesium ions form two layers on either side of the core, like the world's tiniest sandwich, just 6 billionths of a meter across," DeRocher said.

Detecting and visualizing the sandwich structure required scanning transmission electron microscopy at cryogenic temperatures (cryo-STEM) and atom probe tomography (APT). Cryo-STEM analysis revealed the regular arrangement of atoms in the crystals. APT allowed the researchers to determine the chemical nature and position of small numbers of impurity atoms with sub-nanometer resolution.

The researchers found strong evidence that the core-shell architecture and resulting residual stresses impact the dissolution behavior of human enamel crystallites while also providing a plausible avenue for extrinsic toughening of enamel.

"The ability to visualize chemical gradients down to the nanoscale enhances our understanding of how enamel may form and could lead to new methods to improve the health of enamel," Smeets said.

This study builds on an earlier work, published in 2015, in which the researchers discovered that crystallites are glued together by an extremely thin amorphous film that differs in composition from the crystallites.