The Relationship Between Periodontal Disease and Alzheimer's Disease

While each of these conditions is of importance to our aging worldwide population, the link to Alzheimer’s is of particular concern. Over the past few years, a body of evidence has emerged that indicates periodontal disease has the potential to increase the risk of developing Alzheimer’s disease, indicating that much earlier dental diagnosis could improve their outcomes in both oral health and cognitive function.

Findings from studies linking these two conditions have been published in the New York Times as recently as 2020. You can calm any patient concerns around their possible increased risk of developing Alzheimer's by explaining the mechanism of chronic inflammation in both dental and cognitive health, and what steps they can take to improve their oral health.

Chronic inflammation in periodontal disease

Inflammation is a physiological immune response to an injury to the body. In the case of periodontal disease, the injury is the prolonged bacterial infection. Typically, inflammation is acute, lasting long enough for the injury to resolve. If the injury does not resolve, inflammation can become chronic, causing the body’s own immune system to start attacking healthy tissues.

The biofilm of the mouth contains both beneficial and harmful bacteria. When harmful bacteria in plaque cause damage to the gums, individuals can develop gingivitis. Left untreated, this condition can progress to periodontitis, a chronic inflammatory disease. In this case, one of the keystone pathogens responsible for the chronic inflammatory response is Porphyromonas gingivalis. This relationship will be discussed shortly, but first, let’s take a step back to understand the latest research and scientific insight on Alzheimer’s disease itself.

The role of inflammation in Alzheimer’s disease

Alzheimer’s disease is a degenerative disorder of the brain marked by two primary pathologies, characterized by two hallmark proteins in the brain: amyloid beta (Aβ), the first protein that deposits in the brain as Alzheimer’s develops, and tau, which builds up in nerve cells and forms neurofibrillary tangles (NFT). Within the last decade, a third pathology has been added: a sustained immune response in the brain. 

Several researchers have demonstrated that the brains of patients with Alzheimer’s disease show signs of prolonged inflammation.

Sustained immune response is widely recognized as a central feature of neurodegenerative disorders including Alzheimer's disease. This persistent response is associated with the initial Aβ pathology as well as the later development of NFT. The inflammation-fighting gene TREM2 is viewed as a mechanistic factor in this immune response, because when it doesn't function properly, Aβ plaques can build up between neurons and the cleaning process can cause damage to those neurons.

Research linking periodontal disease to Alzheimer's

While inflammation is a key factor in both periodontal disease and Alzheimer’s, the co-causal nature of the two has only recently been studied in-depth.

The recent 2021 study by Kamer et al. shows that older adults with more harmful than healthy periodontal bacteria are more likely to have evidence for amyloid beta in their cerebrospinal fluid. This study adds support to the understanding and evidence that proinflammatory diseases disrupt the clearance of amyloid from the brain and that a connection between periodontitis and Alzheimer’s disease exists.

In a 2019 study conducted by Dominy et al., researchers investigated the presence of Porphyromonas gingivalis in the brains of Alzheimer’s patients. They found that “Oral P. gingivalis infection in mice resulted in brain colonization and increased production of Aβ1-42, a component of amyloid plaques.” Further, gingipains, toxic proteases from Pg, were neurotoxic in vivo and in vitro, exerting detrimental effects on the tau protein. The data suggested that gingipain inhibitors could be valuable for treating Pg brain colonization and neurodegeneration in Alzheimer's disease.

A 2020 study by Demmer et al showed a 22% higher relative risk for developing Alzheimer’s in patients with severe periodontal inflammation. That risk increased to 26% among individuals without teeth.

Further peer review published in 2021 by Ryder and Xenoudi found evidence for the role of “periodontal disease microflora on the initiation and progression of Alzheimer's disease.” This review once again points to the presence of P. gingivalis and gingipain enzymes as mechanisms that promote and exacerbate the mechanism within the Alzheimer’s patient.

Most recently, new research published in the journal Frontiers in Aging Neuroscience by Tufts University scientists and colleagues suggested a link between F. nucleatum – another type of bacteria that commonly proliferates in periodontal disease – and Alzheimer's disease.

"In this study, our lab is the first to find that Fusobacterium nucleatum can generate systemic inflammation and even infiltrate nervous system tissues and exacerbate the signs and symptoms of Alzheimer's disease," said Jake Jinkun Chen, professor of periodontology.

These findings have encouraged additional research. For example, in October of 2021, Columbia University’s College of Dental Medicine announced it has received a $4 million grant from the National Institute of Aging/National Institutes of Health for a study entitled, “A Longitudinal Study of Periodontal Infections and Alzheimer’s Disease: The WHICAP Ancillary Study of Oral Health.”

The five-year study will be led jointly by James M. Noble, MD, MS and Panos N. Papapanou, DDS, PhD, editor-in-chief of the Journal of Clinical Periodontology. 

The risk factors

The ongoing research into Alzheimer’s and its relationship with inflammatory diseases such as periodontitis could ultimately lead to better interventions and preventative plans for Alzheimer’s disease.

The Ryder/Xenoudi review points out that patients who already have reduced cognitive function or are experiencing cognitive decline are at risk for developing exacerbating factors due to “lack of adherence to dental hygiene routines and professional care” which “leads to increases in the prevalence and severity of these dental conditions, leading to increased loss of teeth.”