Research Summary: Periodontal disease as a possible cause for Alzheimer’s disease

A summary of:

Angela R. Kamer, Ronald G. Craig, Richard Niederman, et al. Periodontal disease as a possible cause for Alzheimer’s disease. Periodontol 2000. 2020 Jun:83(1):242-271. doi: 10.1111/prd.12327.

Worldwide, approximately 47 million people have dementia, 60-80% of whom are diagnosed with dementia of the Alzheimer’s type. The prevalence of dementia is supposed to increase to over 100 million by 2050. It is estimated that delaying the onset of Alzheimer’s dementia by just 1 year would decrease the number of cases by more than 9 million by 2050.

Recently, evidence consistently points to chronic inflammatory states as increasing Alzheimer’s disease (AD) risk, raising the question of whether inflammatory conditions, such as periodontitis, may contribute to the incidence and prevalence of AD.

During the last decade, many studies have reported on the relationship between periodontal disease (PD) and dementia, AD, cognitive dysfunction, and decline. The results were mixed; some studies found positive associations, whereas others did not.

A summary of findings from studies reviewed:

  1.  Risk of dementia for those with PD was slightly higher than those with no environmental risks, such as smoking, alcohol, and lack of exercise, suggesting that PD alone can constitute a risk factor.
  2. In a large retrospective cohort of people ≥50 years of age, individuals with 10 years of periodontal exposures (characterised as bone loss and increased pocket depth) were found to be at increased risk of developing AD.
  3. A study spanning 30 years found that PD exposure increased the risk of cognitive decline, especially in those over 45 years of age.
  4. A study of elderly subjects found that those with gingival inflammation but not those with high clinical attachment loss have a greater cognitive decline over a 2-year period compared with those without gingival inflammation.
  5. In a study of 60 elderly subjects, presence of periodontitis was associated with a marked increase in cognitive decline over 6-months independent of baseline cognitive state.
  6. In a prospective cohort of 558 adults aged 52-75 years, followed up for 8 years, found that those with PD did not decline faster than those without.
  7. In a study of two cohorts of 78 and 348 subjects, no relation between PD and AD was found.

These conflicting results may be explained by the diversity of methodologies used, such as design, exposure, and confounding factors. The systemic reviews published also varied in their findings.

Most recently, chronic periodontitis together with infection with P. gingivalis has been identified as a significant risk factor for developing Aβ plaques, dementia, and AD.

Results of multiple studies:

  1. Presence of periodontal bacteria (Spirochetes, treponema denticola, P. gingivalis) found in brains of subjects with AD.
  2. Subgingival samples from subjects with low cerebrospinal fluid Aβ42 (index of brain amyloidosis) were enriched in bacterial taxa characteristic of PD.
  3. Subjects with high cerebrospinal fluid Aβ42 were enriched in bacterial taxa belonging to genera characteristic of periodontal health.
  4. In transgenic mice overexpressing mutated human amyloid precursor protein (hAPP-J20), oral infection with P. gingivalis impaired cognitive function, increased the deposition of AD-like plaques, and resulted in alveolar bone loss compared to control hAPP-J20 mice. 
  5. Evidence of P. gingivalis in brain tissue, spinal fluid and saliva of Alzheimer’s subjects both alive and deceased.
  6. Evidence of gingipains (P. gingivalis virulence factors) in brain tissue of 96% of subjects with AD.
  7. Gingipains inhibitors, when administered peripherally were able to counteract pathological effect of P. gingivalis in brain.

Collectively, these studies show that the PD-derived bacterial species, including P. gingivalis could be involved in pathogenesis of AD.

Based on pathological, mechanistic, clinical, animal, and “in vitro” studies this review showed that PD could induce systemic inflammation, blood-brain barrier disruption, neuroinflammation, brain amyloid, neurodegeneration, and cognitive impairment. As these are well-known pathogenic pathways of AD, we can conclude that PD, through its inflammatory and bacterial burdens, could be “a biologically plausible risk factor” for AD. Although not yet studied, PD-derived herpesviruses could also, independently or synergistically, affect AD pathogenesis. Similarly, although clinical evidence supports these relationships, the strength of evidence is not enough to confirm causality. More longitudinal studies are needed to verify the clinical data reviewed. Based on this, interventional trials could be performed to define causality and the implicated pathways (amyloid β pathology, neurodegeneration, brain glucose metabolism, brain atrophy, and cognition).

Mobina Bohloli BDS4

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