Alzheimer disease and the periodontal patient: New insights, connections, and therapies.

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Loss of cognitive function in the aging population, particular those with Alzheimer disease, presents unique challenges to health practitioners. For the dental practitioner these include management of periodontal diseases, caries, and other dental conditions in this special population. It is well established in the cognitively impaired patient that a lack of adherence to dental hygiene routines and professional care leads to increases in the prevalence and severity of these dental conditions, leading to increased loss of teeth. More recent evidence has indicated a possible role of the microbiota of dental plaque associated with periodontal diseases in the development and progression of Alzheimer disease, thereby supporting a two-way interaction of these two diseases. New therapies are needed to address the potential upstream events that may precede overt signs of Alzheimer disease. One of these approaches would be to target these various bacterial, viral, and other microbial pathogens associated with periodontal disease that can translocate into the bloodstream and then to distal sites, such as the brain. Such microbial translocation would lead to local inflammation and buildup of the hallmark signs of Alzheimer disease, including amyloid beta deposits, tau fragmentation and tangles, breakdown of host protective molecules, such as the apolipoproteins, and neuron toxicity. In this review, evidence for the biological basis of the role of the periodontal disease microflora on the initiation and progression of Alzheimer disease will be presented with a focus on the potential role of the keystone pathogen Porphyromonas gingivalis with its family of gingipain enzymes. The various mechanisms for which P.gingivalis gingipains may contribute to the initiation and progression of Alzheimer disease are presented. Small-molecule inhibitors of these gingipains and their effects on reducing biological markers of Alzheimer disease may have beneficial effects for the initiation and progression of loss of cognitive function in Alzheimer disease. In addition to these targeted therapies for specific periodontal pathogens, considerations for the dental practitioner in applying more general approaches to reducing the periodontal plaque microflora in the management of the cognitively impaired patient are discussed for this special population.