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Periodontal disease and impaired cognition
By Elizabeth (Krall) Kaye, MPH, PhD

Progressive inflammation of tissues in the central nervous system, resulting in degeneration of nerve cells, is thought to play a role in the development of dementia.1 Epidemiologic studies suggest that persons with high levels of systemic inflammatory markers, such as C-reactive protein and pro-inflammatory cytokines, are at higher risk of dementia than those with lower levels. In addition, use of nonsteroidal anti-inflammatory drugs (NSAIDS) may lower the risk of dementia. There are many potential sources of chronic inflammation, including periodontal diseases. Periodontal diseases are among the most prevalent diseases affecting the population. Among adults, 75% have a mild form (gingivitis), and approximately 40% have moderate or severe periodontitis.

Within the past several years, an increasing number of studies have reported associations between oral health status and measures of impaired cognition in community-dwelling older adults.2-7 In the U.S. National Health and Examination Surveys (NHANES) conducted in 1988-1994 and in 2001-2002,2-4 participants underwent cognitive testing to measure memory, response speed, attention, and coordination. Persons with lower scores on these cognitive tests were more likely to have a greater extent of sites with attachment loss and probing pocket depth, or lack teeth altogether, compared to persons with higher scores. In addition, individuals with high serum levels of antibody to P. gingivalis, a common periodontal bacterium, performed poorly on verbal recall and subtraction tasks.2 Other studies found lack of teeth was associated with poor cognitive function5,6 and higher incidence of dementia.7 In the current study, increased risk of cognitive impairment was independently related to number of teeth lost and progression of periodontal disease during a 32-year follow-up.

Since all of these studies have been observational, it cannot be determined yet if periodontal disease directly causes or worsens cognitive impairment, or what biologic mechanisms are responsible for the associations. Several mechanisms have been proposed and are the focus of current research.

Periodontal disease as a source of inflammatory factors

Periodontitis is a chronic condition that exposes a patient to pro-inflammatory factors over the long term. Periodontal pathogens that accumulate in plaque on the teeth secrete lipopolysaccharide, an endotoxin that activates macrophages to produce pro-inflammatory cytokines. In turn, these cytokines enter the circulation and induce the host response through several pathways. In addition, the bacteria themselves and their components can gain access to the systemic circulation and invade non-oral tissues. Thus, bacteria and inflammatory mediators that originate in the oral cavity may contribute to and enhance inflammatory processes in the brain that increase the risk of dementia.

Periodontal disease as a marker for underlying inflammatory processes that lead to cognitive impairment

The association between periodontal disease and cognitive impairment may also reflect an indirect biologic mechanism in which periodontitis and dementia are two separate disease outcomes that arise from an underlying chronic inflammation. Both diseases have several common risk factors that can influence the immune system and enhance inflammation, including smoking, depression, and diabetes. In both periodontitis and dementia, specific genotypes of the interleukin family of cytokines have been associated with increased disease risk and led to the hypothesis that some individuals have a hyper-inflammatory response phenotype. A number of diseases with an inflammatory component — cardiovascular disease, diabetes, periodontal disease, and dementia — might then tend to cluster in individuals with such a phenotype.

Dr. Elizabeth (Krall) Kaye is a professor and director of the epidemiology division in the Department of Health Policy & Health Services Research at Boston University Henry M. Goldman School of Dental Medicine. Her research focuses on the association of skeletal bone density to tooth retention in the elderly, genetic and environmental influences on bone and teeth, and smoking cessation. She holds an MPH and PhD from the University of Pittsburgh.

References:
  1. Kamer AR, Craig RG, Dasanayake AP, Brys M, Glodzik-Sobanska L, deLeon MJ. Inflammation and Alzheimer’s disease: possible role of periodontal diseases. Alzheimer’s Dementia 2008; 4:242-250.
  2. Noble JM, Borrell LN, Papapanou PN, Elkind MSV, Scarmeas N, Wright CB. Periodontitis is associated with cognitive impairment among older adults: analysis of NHANES-III. J Neurol Neurosurg Psychiatry 2009; 80:1206-1211.
  3. Stewart R, Sabbah W, Tsakos G, D’Aiuto F, Watt RG. Oral health and cognitive function in the Third National Health and Nutrition Examination Survey (NHANES III). Psychosomat Med 2008; 70:936–941.
  4. Yu YH, Kuo HK. Association between cognitive function and periodontal disease in older adults. J Amer Geriatrics Soc 2008; 56:1693–1697.
  5. Stewart R, Hirani V. Dental health and cognitive impairment in an English National Survey Population. J Amer Geriatric Soc 2007; 55:1410–1414.
  6. Grabe HJ, Schwahn C, Völzke H, et al. Tooth loss and cognitive impairment. J Clin Periodontol 2009; 36:550-557.
  7. Sparks Stein P, Desrosiers M, Donegan SJ, et al. Tooth loss, dementia, and neuropathology in the Nun Study. J Amer Dent Assoc 2007; 138:1314–1322.