The Studies don’t lie……..
This study is designed to obtain data exploring the role of periodontal disease in the pathogenesis of Alzheimer’s disease. PD is a chronic infection resulting from the interaction of periodontopathic bacteria and a host response. This interaction leads to localized and systemic inflammation characterized by elevation of inflammatory molecules such as IL-1ß, IL-6, IL8, TNF-? ?, CRP; and , high antibodies levels. PD through bacteria and/or inflammatory molecules may contribute to already elevated brain inflammatory molecules, therefore increasing risk of AD. We hypothesize that subjects with periodontal infections will be at an increased risk of developing AD. Objectives: We will determine whether a greater proportion of subjects developing AD had elevated levels of antibody titers to Aa, Pg, Td and Tf (markers of periodontopathic bacteria) and of systemic inflammatory markers (IL-1ß, Il-6, TNF-? ?, CRP and others) at baseline as compared control subjects. Methods: Stored plasma samples collected at baseline evaluation at the NYU ADCC and the affiliated CBH from cohorts of subjects are used in a nested case-control. Cases (AD) and Controls (NL, MCI) will be compared for the existence of exposures at baseline (antibodies to Aa, Pg, Td, Tf, CRP and cytokines). In this project we characterized the study population using several parameters, such as age, gender and race. Results: Since cytokine levels may differ based on the year of collection we characterized our study population by year. Our results showed that in 1998, 1999, 2000 and 2001 age was statistically greater in AD subjects compared to controls. In 1997 and 2004 age difference approached statistical significance. In contrast there was no significant difference in gender and race among groups. Conclusion: Our results showed that AD subjects are older than controls subjects suggesting that this parameter has to be considered in the final study analysis.] Akhtar S, Kamer AR. IADR General Session, Miami, FL April 2009. http://iadr.confex.com/iadr/2009miami/webprogram/Paper119192.html
STUDY 2: Inflammation and Alzheimer’s disease
Possible role of periodontal diseases. 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.] Kamer AR, Craig RG. et al. Alzheimer’s & Dementia, Vol 4, Issue 4, pp242-250, July 2008. http://www. alzheimersanddementia.com/article/S1552- 5260(07)00621-8/abstract
STUDY 3: Inflammation Linked to Alzheimer’s Disease.
Exposure to inflammation early in life quadruples one’s risk of developing Alzheimer’s disease, said researchers in a presentation on June 19 at the first Alzheimer’s Association International Conference on Prevention of Dementia in Washington. A research team led by Margaret Gatz, Ph. D. (a professor of psychology at the University of Southern California) and including researchers from the Karolinska Institute in Stockholm, Sweden, sifted through data on the 20,000 participants in the Swedish Twin Registry and found 109 “discordant” pairs of twins in which only one twin had been diagnosed with dementia. Previous studies by Dr. Gatz and colleagues have shown that Alzheimer’s disease is strongly genetic; if one twin has the disease, his or her identical twin has a 60 percent chance of developing it. Information about participants’ education, activities and health histories came from surveys they completed in the 1960s, when the registry was created, as well as from hospital discharge records. The surveys included questions about loose or missing teeth. Researchers used the answers to the dental-related questions to build a crude indicator of periodontal disease. They concluded that an inflammatory burden early in life, as represented by chronic periodontal disease, might have severe consequences later. “If what we’re indexing with periodontal disease is some kind of inflammatory burden, then it is probably speaking to general health conditions,” said Dr. Gatz. If the link between inflammation and periodontal disease is confirmed, researchers said it would add inflammatory burden to the short list of preventable risk factors for Alzheimer’s disease. ] News – J Am Dent Assoc, Vol 136, No 8, 1084. http://jada.ada.org/cgi/content/ full/136/8/1084-a
STUDY 4: Inflammatory Markers and Cognition in well-functioning African-American and White Elders.
Serum markers of inflammation, especially IL-6 and CRP, are prospectively associated with cognitive decline in well-functioning elders. These findings support the hypothesis that inflammation contributes to cognitive decline in the elderly.] Yaffe, K, Lindquist K, et al. Neurology 2003;61:76-80. http://www.neurology.org/cgi/content/abstract/61/1/76 Inflammation Linked to Cognitive Decline. [Inflammation is increasingly being implicated as a major factor contributing to several age-related diseases, including Alzheimer’s and dementia. Now, researchers at the San Francisco VA Medical Center (SFVAMC) have found a link between inflammation and early cognitive decline in otherwise healthy individuals.] J Neurology July 8, 2003 Yaffe, K, http://www.ncire.org/yaffe6.html
STUDY 5: The Inflammatory Response in Alzheimer’s Disease.
Over the last 2 decades, numerous innate inflammatory mediators have been reported to be upregulated in pathologically vulnerable regions of the brain in Alzheimer’s disease (AD). These data have led to a reexamination of the dogma of brain immunologic privilege and to new studies that examine the role of the innate inflammatory response in a number of other neurologic disorders, particularly Parkinson’s disease and human immunodeficiency virus dementia. In addition, basic science discoveries about neuroinflammation are now beginning to move to the clinic. More than 20 epidemiologic surveys have consistently demonstrated that common non-steroidal antiinflammatory drugs may protect against the development of AD. By contrast, anti-inflammatory treatment trials for existing AD have typically shown little to no effect on halting or reversing the disorder, although the agents tested have often been at odds with those suggested by the epidemiologic and basic science results. The extensive literature on innate inflammation and neurologic disease notwithstanding, three fundamental questions still remain to be answered fully. First, are innate inflammatory responses a cause of neurologic disease or merely a more sophisticated means than previously imagined for removing the detritus left by more primary pathogenic mechanisms? Second, can anti- antiinflammatory agents effectively treat inflammatory existing neurologic disease, or is a protective strategy in high-risk patients the only reasonable option? Third, whether for protection or treatment, what is the best choice of anti-inflammatory agent given the basic science mechanisms and epidemiologic results that have been reported? .This article summarizes some of the key inflammatory mechanisms that have been elucidated in AD, their potential significance in causing neurodegeneration rather than simply removing it, and the generally problematic attempts that have been made to apply anti-inflammatory approaches to the treatment or prevention of AD.] Rogers J. Journal of Periodontology, 2008, Vol. 79, No. 8s, Pages 1535-1543 1543, http://www.joponline.org/doi/full/10.1902/jop.2008.080171