Fig. 1

Bielschowsky stained neuritic plaque from an individual with AD. Specimen provided by Dr. Stephen Scheff, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY.

IL- 1 is particularly relevant to the pathogenesis of AD since it is overexpressed in neuritic plaques.¹³³ In addition, IL- 1 increases synthesis of beta–amyloid precursor protein and activates astrocytes.¹³⁴

Given the evidence for the role of chronic inflammation in AD,¹³³ it is reasonable to suggest that long-term systemic exposure to periodontal pathogens and their subsequent chronic production of inflammatory mediators may precipitate neuropathological changes.

Periodontal Disease Increases the Risk of Cerebrovascular Injury to Brain Stroke, or cerebrovascular accident, affects the blood supply to the brain. There are two types of stroke: hemorrhagic, in which an artery supplying oxygen-rich blood to the brain ruptures, and ischemic, when a blood vessel supplying the brain is blocked by a local thrombus or an aggregation of bacteria and fibrin from a distant source.⁷⁷ Although stroke is not considered a major risk factor for AD,¹³⁵ stroke has been related to the severity of clinical symptoms in Alzheimer’s patients,¹³⁶ and individuals with a history of stroke demonstrate more rapid decline in memory performance than do healthy individuals.¹³⁷ Stroke is a significant risk factor for dementia.¹³⁵ In fact, the risk of dementia increases ninefold in subjects experiencing ischemic stroke.¹³⁹ The relationship between stroke and periodontal disease thus merits discussion.

Recent findings suggest that periodontal disease is an important risk factor for stroke.¹⁴⁰ Beck and colleagues found that persons with severe periodontal bone loss at baseline had nearly 3 times the chance of experiencing a cerebrovascular accident (CVA) compared with those with

minimal bone loss or no periodontal disease.¹⁴⁰ Elter and colleagues examined 9,415 dentate and 1,491 edentulous adults and found stroke associated with both edentulism and clinical attachment loss of 3 millimeters or greater.¹⁴¹ Findings from similar studies by Grau and colleagues indicate that subjects with severe periodontal disease, as defined by clinical attachment loss of 6 mm or greater, had from 4.3¹⁴² to 7.4¹⁴³ times greater risk of cerebral ischemia than control subjects or subjects with mild periodontal disease. In an investigation of plaque index scores and oral hygiene practices of 401 US veterans, it was shown to have a significant association with stroke.¹⁴⁴ Examining subjects under the age of 50, Syrjänen and colleagues found a greater risk of ischemic cerebrovascular disease in males with severe dental infections combined with other bacterial infections.¹⁴⁵ In a case control study, patients with acute cerebrovascular ischemia were found to have more severe periodontal disease when compared with age and sex-matched nonstroke patient controls.¹⁴³ In addition, men who have 24 or fewer teeth have been shown to have a greater risk of stroke.¹⁴⁶

What mechanism underlies the association between periodontal disease and stroke? Li suggests that in individuals with periodontal disease bacteria and cytokines disseminating into the systemic circulation contribute to stroke by altering platelet function and promoting atherosclerosis and blood coagulation, a hypothesis supported in the literature.⁷⁷ Proinflammatory mediators (IL- 1, TNF-α, PGE2, and IL- 6) produced in response to the bacterial challenge of periodontal disease induce the release of platelet activating factor (PAF).¹⁰⁸ Platelet aggregation-associated protein expressed on the periodontal pathogen P. gingivalis has been found to induce platelet aggregation, potentially increasing the chance of acute thromboembolic events.^147-149 In addition, P. gingivalis can activate endothelial cells.¹⁵⁰ Individuals with periodontitis have been found to have significantly higher levels of serum fibrinogen.¹⁵¹ As noted, periodontal pathogens have been found in human artheromas. Haraszthy and colleagues found that 44% of human atheromas removed during carotid endarterectomies tested positive for at least one of the following periodontal pathogens: A. actinomycetemcomitans, Bacteroides forsythus, P. gingivalis, or Prevotella intermedia.¹⁵² In a similar study by Zambon and colleagues, periodontal pathogens were found in over half of the atheromas examined.¹⁵³

Data from recent studies thus indicates that periodontal disease affects platelets and blood coagulation, influences thrombus formation, and activates endothelial cells, all of which contribute to the onset of stroke and could potentially result in the types of neuropathology associated with cognitive impairment.