From the LA Times Health section

June 27, 2005 MEDICINE Possible Alzheimer’s signpost
Gum inflammation may be linked to increased risk of the brain disorder.

By Kevin W. McCullough, Times Staff Writer

Missing teeth and gum disease at an early age may be linked to an increased
risk of Alzheimer’s disease, researchers have found, bolstering the
increasingly strong connection between early exposure to chronic
inflammation and the degenerative brain disorder.

The study, among the findings presented last week at the first Alzheimer’s
Assn. International Conference on Prevention of Dementia, examined lifestyle
factors of more than 100 pairs of identical twins. All of the pairs included
one twin who had developed dementia and one who hadn’t. Because identical
twins are genetically indistinguishable, the study involved only risk
factors that could be modified to help protect against dementia.

Twins who had severe periodontal disease before they were 35 years old had a
fivefold increase in risk of developing Alzheimer’s disease, the researchers
found.

Lead author Margaret Gatz, a psychology professor at USC, cautioned that the
link between periodontal disease and Alzheimer’s doesn’t mean that extra
flossing will reduce that risk.

“We’re not saying, ‘Brush your teeth: Prevent Alzheimer’s disease,’ at all.
That would be an overly simplistic explanation,” Gatz said.

Instead, periodontal disease may be a marker for chronic exposure to disease
that provokes an inflammatory response. Chronic inflammation can damage
tissue, including the brain, which may contribute to the development of the
disease.

“I would think of the periodontal disease as a signpost, not a cause,” Gatz
said.

Periodontal disease is also linked to general health, she pointed out, and
even the inflammatory link to Alzheimer’s may involve several factors.

In contrast to other researchers’ findings, Gatz and her colleagues did not
find that more education or mentally challenging leisure activities reduced
the risk of developing Alzheimer’s. Many experts and the Alzheimer’s Assn.
have recommended regular mentally stimulating activities.

The study teased apart the genetic and environmental factors that increase
the risk of Alzheimer’s disease and showed the inflammation link more
clearly than any previous research, said Huntington Potter, the Eric
Pfeiffer-endowed chair for research on Alzheimer’s disease at the University
of South Florida.

“This finding reinforces a long-standing appreciation . that indicated
inflammation in the brain was an essential part of the disease process,”
Potter said.

In other highlights from the Washington, D.C., conference:

.  By measuring a decline in glucose metabolism in the hippocampus, an
important memory center in the brain, researchers at New York University
School of Medicine were able to predict the development of Alzheimer’s
disease with 85% accuracy nine years before symptoms appeared.

.  Drinking fruit and vegetable juices is associated with a reduced risk of
Alzheimer’s, said researchers at the University of South Florida, based on a
study of 1,800 Japanese Americans. People who drank juice more than three
times a week had a 75% reduced risk compared with people who drank juice
less than once a week.

.  A simple blood test measuring the levels of a protein associated with
Alzheimer’s may be able to determine whether a person develops the disease
in the future, according to researchers at the Mayo Clinic in Jacksonville,
Fla. Study participants with the lowest levels of the protein had triple the
risk of developing Alzheimer’s disease.

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Periodontal Disease and Risk of Cerebrovascular Disease

The First National Health and Nutrition Examination Survey and Its Follow-up Study

Tiejian Wu, MD, PhD; Maurizio Trevisan, MD, MS; Robert J. Genco, DDS, PhD; Joan P. Dorn, PhD; Karen L. Falkner, PhD; Christopher T. Sempos, PhD

Arch Intern Med. 2000;160:2749-2755.

Background  Periodontal disease has been found to be a potential risk factor for coronary heart disease. However, its association with cerebrovascular accidents (CVAs) is much less studied.

Methods  This study examines the association between periodontal disease and CVA. The study cohort comprises 9962 adults aged 25 to 74 years who participated in the First National Health and Nutrition Examination Survey and its follow-up study. Baseline periodontal status was categorized into (1) no periodontal disease, (2) gingivitis, (3) periodontitis, and (4) edentulousness. All CVAs (International Classification of Diseases, Ninth Revision [ICD-9], codes 430-438) were ascertained by hospital records for nonfatal events and death certificates for fatal events. The first CVA, nonfatal or fatal, was used to define incidence. Relative risks were estimated by hazard ratios from the Cox proportional hazard model with adjustment for several demographic variables and well-established cardiovascular risk factors. Weights were used to generate risk estimates.

Results  Periodontitis is a significant risk factor for total CVA and, in particular, nonhemorrhagic stroke (ICD-9, 433-434 and 436-438). Compared with no periodontal disease, the relative risks (95% confidence intervals) for incident nonhemorrhagic stroke were 1.24 (0.74-2.08) for gingivitis, 2.11 (1.30-3.42) for periodontitis, and 1.41 (0.96-2.06) for edentulousness. For total CVA, the results were 1.02 (0.70-1.48) for gingivitis, 1.66 (1.15-2.39) for periodontitis, and 1.23 (0.91-1.66) for edentulousness. Increased relative risks for total CVA and nonhemorrhagic stroke associated with periodontitis were also seen in white men, white women, and African Americans. Similar results were found for fatal CVA.

Conclusion  Periodontal disease is an important risk factor for total CVA and, in particular, nonhemorrhagic stroke.

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Anaerobic bacteria in 118 patients with deep-space head and neck infections from the University Hospital of Maxillofacial Surgery, Sofia, Bulgaria

Lyudmila Boyanova1,, Rossen Kolarov2, Galina Gergova1, Elitsa Deliverska2, Jivko Madjarov2, Milen Marinov2 and Ivan Mitov11 Department of Microbiology, Medical University of Sofia, Zdrave Street 2, 1431 Sofia, Bulgaria

The aim of this study was to assess the incidence and susceptibility to antibacterial agents of anaerobic strains in 118 patients with head and neck abscesses (31) and cellulitis (87). Odontogenic infection was the most common identified source, occurring in 73 (77.7 %) of 94 patients. The incidence of anaerobes in abscesses and cellulitis was 71 and 75.9 %, respectively, and that in patients before (31 patients) and after (87) the start of empirical treatment was 80.6 and 72.4 %, respectively. The detection rates of anaerobes in patients with odontogenic and other sources of infection were 82.2 and 71.4 %, respectively.

In total, 174 anaerobic strains were found. The predominant bacteria were Prevotella (49 strains),Fusobacterium species (22), Actinomyces spp. (21), anaerobic cocci (20) and Eubacterium spp. (18). Bacteroides fragilis strains were isolated from 7 (5.9 %) specimens. The detection rate ofFusobacterium strains from non-treated patients (32.2 %) was higher than that from treated patients (13.8 %). Resistance rates to clindamycin and metronidazole of Gram-negative anaerobes were 5.4 and 2.5 %, respectively, and those of Gram-positive species were 4.5 and 58.3 %, respectively. One Prevotella strain was intermediately susceptible to ampicillin/sulbactam.

In conclusion, the start of empirical treatment could influence the frequency or rate of isolation ofFusobacterium species. The involvement of the Bacteroides fragilis group in some head and neck infections should be considered.

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Possible Contribution from Periodontal Infections, Model and Hypothesis Journal Journal of Alzheimer’s Disease Publisher IOS Press ISSN 1387-2877 (Print) 1875-8908 (Online) Issue Volume 13, Number 4 / 2008 Category Review Article Pages 437-449

Authors

Angela R. Kamer1, Ananda P. Dasanayake2, Ronald G. Craig1, Lidia Glodzik-Sobanska3, Miroslow Bry3, Mony J. de Leon3, 41Department of Periodontics and Implant Dentistry and Basic Sciences, NYU College of Dentistry, New York, NY, USA
2Department of Epidemiology, NYU College of Dentistry, New York, NY, USA
3Department of Psychiatry, Center for Brain Health, NYU School of Medicine, New York, NY 10016, USA
4Nathan Kline Institute, Orangeburg, NY, USA

Abstract

Alzheimer’s disease (AD) affects approximately 4.5 million people in the U.S. and this number will increase as the population ages and the life-span increases. Therefore, of paramount importance is identifying mechanisms and factors that affect the risk of developing AD. The etiology and pathogenic mechanisms for AD have not been defined, although inflammation within the brain is thought to play a role. Consistent with this hypothesis, studies suggest that peripheral infections contribute to the inflammatory state of the central nervous system. Periodontitis is a prevalent, persistent peripheral infection associated with gram negative, anaerobic bacteria that are capable of exhibiting localized and systemic infections in the host. This review offers a hypothetical link between periodontitis and AD and will present possible mechanistic links between periodontitis related inflammation and AD. It will review the pathogenesis of periodontitis and the mechanisms by which periodontal infections may affect the onset and progression of AD. Since periodontitis is a treatable condition, it may be a readily modifiable risk factor for AD.

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Alzheimers Dement. 2008 Jul;4(4):242-50. Epub 2007 Dec 21.

Inflammation and Alzheimer’s disease: possible role of periodontal diseases.

Kamer AR, Craig RG, Dasanayake AP, Brys M, Glodzik-Sobanska L, de Leon MJ.Department of Periodontology and Implant Dentistry, College of Dentistry, New York University, New York, NY, USA. [email protected]

The molecular and cellular mechanisms responsible for the etiology and pathogenesis of Alzheimer’s disease (AD) have not been defined; however, inflammation within the brain is thought to play a pivotal role. Studies suggest that peripheral infection/inflammation might affect the inflammatory state of the central nervous system. Chronic periodontitis is a prevalent peripheral infection that is associated with gram-negative anaerobic bacteria and the elevation of serum inflammatory markers including C-reactive protein. Recently, chronic periodontitis has been associated with several systemic diseases including AD. In this article we review the pathogenesis of chronic periodontitis and the role of inflammation in AD. In addition, we propose several potential mechanisms through which chronic periodontitis can possibly contribute to the clinical onset and progression of AD. Because chronic periodontitis is a treatable infection, it might be a readily modifiable risk factor for AD.

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Bacteria Shown To Cause Blood Clots

Science News

04 Nov 2008

Bacteria can directly cause human blood and plasma to clot – a process that was previously thought to have been lost during the course of vertebrate evolution, according to new research at the University of Chicago, National Institute of Allergy and Infectious Diseases, and Institut Pasteur in Paris. Their findings were published online Nov. 2 inNature Chemical Biology.

The discovery will improve scientists’ understanding of coagulation during bacterial infections and may lead to new clinical methods for treating serious medical conditions such as sepsis and anthrax.

It has long been known that blood often coagulates during sepsis or bacterial infections, but this has generally been regarded as a host’s immune and inflammatory response. It also has been known that bacteria can activate factors that precede coagulation, but it had not previously been known that bacteria can pass the coagulation threshold and cause blood clots to form. Once they form, the clots can grow and propagate. Although this may help prevent the dissemination of the bacteria through the host, it often leads to serious vascular damage due to blocked and injured blood vessels.

The key to clot formation is the location of the bacteria, rather than the total number of bacteria or their level of concentration. In other words, for those bacteria that can activate coagulation factors, coagulation occurs only when a cluster of bacteria forms.

“Our research demonstrates that coagulation can be controlled by changing the spatial distribution, or clustering, of bacteria,” said study co-author Christian Kastrup, Post-Doctoral Assistant at the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology. “Therefore, considering the location of bacterial cells, instead of just their presence or absence and their total numbers, could significantly change our understanding of coagulation.”

Kastrup, who worked on this research as a graduate student in the Ismagilov Lab at the University of Chicago’s Department of Chemistry, is the first author of the Nature paper. Rustem Ismagilov, Professor of Chemistry at the University of Chicago, is the corresponding author. Researchers at the National Institute of Allergy and Infectious Diseases, Institut Pasteur in Paris, and Ben-May Department for Cancer Research at the University of Chicago co-authored the paper.

Coagulation can occur if enough proteases that activate coagulation accumulate near the bacteria, rather than diffuse away. This research used Bacillus anthracis, the anthrax-causing pathogen (using a safe strain that does not infect humans). It found that in the case of human blood, coagulation required the secretion of zinc metalloprotease InhA1, which activated prothrombin and factor X directly – not via factor XII or tissue-factor pathways.

“We refer to this mechanism as ‘quorum acting’ to distinguish it from quorum sensing, in which bacteria coordinate certain actions based, in part, on their density,” said Wei-Jen Tang, Professor at the Ben-May Department for Cancer Research.

This work opens up a new field of st
udy, he added. “We will now explore the commonality of quorum acting, and how quorum acting can affect evolutionary dynamics.”

The results of this research have broad implications, according to Ismagilov. “The work emphasizes the importance of bacteria’s spatial distribution, rather than just its average concentration in the functioning of nonlinear biochemical networks,” he said.

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Journal of Thrombosis and Haemostasis Infection with a periodontal pathogen induces procoagulant effects in human aortic endothelial cellsG.A. Roth*, B. Moser*, S.J. Huang, J.S. Brandt, Y. Huang, P.N. Papapanou, A.M. Schmidt*, E. Lalla  Summary Background: Multiple studies have demonstrated a link between periodontal infections and vascular disease. Porphyromonas gingivalis, a major periodontal pathogen, has been shown to adhere to and invade endothelial cells. Objective: In order to dissect mechanisms underlying these observations, we assessed the role of P. gingivalisinfection in modulating properties of endothelial cells linked to atherothrombosis.Methods: Primary human aortic endothelial cells (HAEC) were infected with either P. gingivalis 381 or its non-invasive fimbriae-deficient mutant, DPG3. Markers of coagulation and thrombosis were assessed 8h and 18h post-infection in cell lysates and supernatants. Results: Infection with P. gingivalis 381 significantly enhanced tissue factor expression and activity, and suppressed levels of tissue factor pathway inhibitor. Further, P. gingivalis infection decreased levels and activity of tissue plasminogen activator, and enhanced plasminogen activator inhibitor-1 antigen and activity. Consistent with an important role for bacterial adhesion/invasion in this setting, infection with DPG3 failed to induce procoagulant properties in HAEC. Most of the above effects of P. gingivalis 381 were more apparent at the later time point (18h post-infection). This suggests that P. gingivalis infection, rather than having an immediate and direct effect, might activate pathways that, in turn, trigger endothelial procoagulant mechanisms. Conclusions: Taken together these data demonstrate for the first time that infection with a periodontal pathogen induces procoagulant responses in HAEC.

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1: Anaerobe. 2007 Oct 4

Detection of Dialister pneumosintes in the subgingival biofilm of subjects with periodontal disease.

Ferraro CT, Gornic C, Barbosa AS, Peixoto RJ, Colombo AP.Dialister pneumosintes has been indicated as a potentially new periodontopathic species. This study evaluated the prevalence of this microorganism in saliva and subgingival biofilm from subjects with different periodontal conditions. Subgingival biofilm and saliva samples from 48 subjects with periodontal health (PH) and 116 patients with chronic periodontitis (CP) were obtained. DNA was extracted from the samples and the presence of D. pneumosintes was determined by PCR. Differences in clinical parameters and frequency of D. pneumosintes between groups were sought by Mann-Whitney, Chi-square and Fisher’s exact tests. Overall, D. pneumosintes was detected in 47.8% of the biofilm samples, but only in 3% of saliva samples. CP patients presented a significantly greater mean prevalence of this species in sites with periodontal health and periodontal infection (43.5+/-7.4% and 62.1+/-6.4%, respectively) than PH subjects (29.4+/-7.9%) (Mann-Whitney; p<0.01). Moreover, significant associations between the prevalence of D. pneumosintes and pocket depth (p=0.001), attachment loss (p=0.001) and bleeding on probing (GLM, p=0.014) were observed after adjusting for age and gender. These findings corroborate the association of D. pneumosintes with periodontitis.

AND…

J Clin Microbiol. 2002 October; 40(10): 3871–3873. doi: 10.1128/JCM.40.10.3871-3873.2002.

Abstract In this report, we review two cases of brain infection due to Dialister pneumosintes in previously healthy patients. The bacterium was isolated from the first patient by blood culture and directly from a brain abscess in the second patient. In both cases, the infection was suspected to be of nasopharyngeal or dental origin. The patients had favorable outcomes following surgical debridement and antibiotic treatment. After in vitro amplification and partial sequencing of the 16S rRNA gene, two strains were classified as D. pneumosintes. However, traditional biochemical tests were not sufficient to identify the bacteria. In addition to causing periodontal and opportunistic infections, D. pneumosintes, contained in mixed flora, may behave as a clinically important pathogen, especially in the brain. In addition to phenotypic characterization, 16S rRNA partial sequencing was used to identify D. pneumosintes definitively.

AND…

Cytomegalovirus periodontal presence is associated with subgingival Dialister pneumosintes and alveolar bone loss

Authors: Slots J.1; Sugar C.2; Kamma J.J.3

Source: Oral Microbiology and Immunology, Volume 17, Number 6, December 2002 , pp. 369-374(6)

Abstract:

Destructive periodontal disease is associated with human cytomegalovirus (HCMV), Epstein-Barr type 1 virus (EBV-1) and other members of the Herpesviridae family as well as with various gram-negative anaerobic bacteria, including the Dialister pneumosintes species. This study aimed to determine possible interrelationships between periodontal HCMV, EBV-1, herpes simplex virus and D. pneumosintes, and relate the microbiological findings to periodontitis clinical status. Sixteen subjects each contributed paper point samples from two progressing and two stable periodontitis lesions, as determined by ongoing loss of probing attachment. Polymerase chain reaction methodology was used to identify the study herpesviruses and D. pneumosintes. Chi-squared tests, Fisher exact tests and multivariate logistic regression were employed to identify statistical associations among herpesviruses, bacteria and clinical variables. HCMV, and no other virus or combination of viruses, was positively associated with the presence of D. pneumosintes, and the relationship was specific for individual periodontitis sites with no detectable subject effect. D. pneumosintes was in turn positively associated with periodontal pocket depth and disease-active periodontitis. When the average percentage of alveolar bone loss in all teeth was treated as a response, HCMV remained significant even after D. pneumosintes was included in the model, suggesting that both HCMV and D. pneumosintes affected bone loss or, alternatively, HCMV affected factors not studied that themselves can induce bone loss. We hypothesize that periodontal HCMV sets the stage for subgingival proliferation of D. pneumosintes and subsequent periodontal disease progression. Studies on herpesviral–bacterial interactions may hold great promise for delineating important etio-pathogenic aspects of destructive periodontal disease.

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Aetna And Columbia Announce Results From Study Showing Relationship Between Periodontal Treatment And A Reduction In The Overall Cost Of Care For Three Chronic Conditions

HARTFORD, Conn., March 20, 2006 — Aetna (NYSE: ΑET) and Columbia University College of Dental Medicine conducted a study that found a relationship between periodontal (gum) treatment and the overall cost of care for several chronic diseases. The results of the study, which included approximately 145,000 Aetna members with continuous dental and medical coverage, indicate that periodontal care appears to have a positive effect on the cost of medical care, with earlier treatment resulting in lower medical costs for members with diabetes, coronary artery disease (CAD), and cerebrovascular disease (CVD) or stroke.

“The results of this study are encouraging because they show the connection between good oral health and overall well-being, as well as illustrating that the early treatment of periodontal disease can help reduce medical costs for these conditions,” said Pat Farrell, head of Aetna Specialty Products. “We believe that in addition to lowering medical costs, we are also helping to improve members’ quality of life. We will continue to work with Columbia to demonstrate ways that dental care can improve the overall health of our members.”

“Systemic health is often associated with the condition of the oral cavity in that many systemic diseases manifest in the mouth; however, less is known about the connection between a diseased periodontium and the impact it may have on systemic health,” said David A. Albert, D.D.S., M.P.H., Associate Professor of Dentistry at Columbia University. “The association between periodontal infection and systemic health has important implications for the treatment and management of patients.”

The retrospective study of claims data included an examination of approximately 145,000 members participating in Aetna PPO plans with continuous dental and medical coverage over two years. Periodontal care appeared to have a positive effect on the cost of medical care in this two-year study (2001, 2002), with earlier treatment resulting in lower medical costs for diabetes, CVD and CAD. In addition, the actual cost of medical care for patients with diabetes and CAD was found to be lower if they received periodontal care in the first year of the study.