Research Suggests Alzheimer Disease and Periodontal Disease Are Linked by Inflammation

Alzheimer disease (AD) is a progressive neurologic disorder that causes deterioration in memory, thinking, and behavior. Its prevalence continues to increase, impacting approximately half of all patients aged 85 years.¹

Evidence has increasingly suggested that neuroinflammation plays a key role in the progression of AD.² As highlighted in a 2024 review, periodontitis has been identified as a risk factor for AD.¹ Periodontitis is characterized by colonization of the oral cavity by pathogenic bacteria which can then penetrate the surrounding epithelium. Like AD, periodontitis is more common among elderly patients and is chronic in 68% of those older than 65 years.¹

Image credit: fotogurmespb | stock.adobe.com

In response to oral pathogens, microglial cells are activated and inflammatory mediators such as cytokines are released. In a healthy host, this acute response resolves over time via active biochemical and metabolic processes. Lipid mediators, including lipoxins, mediate resolution of inflammation.

Patients with AD have a reduced ability to resolve inflammation. This can lead to persistent inflammation associated with overall neurodegeneration and cognitive impairment.^1,2 This immune response may exacerbate AD-specific pathologies as well, such as increasing β-amyloid plaque and neurofibrillary tangle development.

The Role of Medications

Periodontitis and AD are both characterized by inflammatory and immunological response by the host. Therefore, anti-inflammatory medications such as non-steroidal anti-inflammatory drugs (NSAIDs) may be reasonable options to target both disease states. Although efforts have been made to incorporate NSAIDs into the treatment of periodontitis, clinical trials demonstrating impact on periodontal health are lacking and the risk-benefit ratio has not been established.

Studies have evaluated the use of NSAIDs in AD for several decades. Cyclooxygenase (COX)-2 is highly expressed in degenerative cells in the brain. NSAIDs can reduce AD symptoms by inhibiting COX. Independently of COX inhibition, NSAIDs may prevent the buildup of β-amyloid plaques by decreasing their synthesis. Aspirin has also demonstrated the ability to impact lipoxins by making them more “resistant” to inactivation and enhancing resolution signaling.^1,3

Conclusion

The authors of this review concluded that although the link between inflammatory cytokines and cognitive functioning has been definitively established, the mechanism connecting this response from the periodontium to the brain is not known. NSAIDs cannot be recommended as a component of standard periodontal therapy until more rigorous studies have been completed.

References

1. Hashim N, Babiker R, Mohammed R, et al. Highlighting the effect of pro-inflammatory mediators in the pathogenesis of periodontal diseases and Alzheimer’s disease. J Pharm Bioallied Sci. 2024;16(Suppl 2):S1120-S1128

2. Kinney JW, Bemiller SM, Murtishaw AS, et al. Inflammation as a central mechanism in Alzheimer’s disease. Alzheimer’s Dement (NY). 2018;4:575-90

3. Takano T, Fiore S, Maddox JF, et al. Aspirin-triggered 15-epi-lipoxin A4 (LXA4) and LXA4 stable analogues are potent inhibitors of acute inflammation: evidence for anti-inflammatory receptors. J Exp Med. 1997;185(9):1693-704