Approved Research

Correlation of periodontitis with morbidity and mortality in Alzheimer's disease and its molecular mechanisms

Lay summary

To explore the relationship between periodontal disease (PD) and the morbidity and mortality of Alzheimer's disease and its molecular mechanisms.

PD is one of the most common inflammatory diseases in humans and can cause destruction of soft and hard periodontal tissues, ultimately leading to tooth movement and loss. It is caused by a dysbiosis of the oral microbiota and is associated with a dysregulated immune inflammatory response. The response caused by bacterial build-up on the tooth surface is not confined to the mouth, but is also involved in the progression of systemic inflammation through the digestive tract or bloodstream.

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease that occurs in middle-aged and elderly populations and is characterised by irreversible and progressive memory loss and cognitive impairment due to neuronal death. Current research suggests that there is a correlation between AD and PD. It has also been suggested that patients with AD often have poor periodontal health, leading to persistent infection of their periodontal tissues.The periodontal status of patients with AD is receiving increasing attention, particularly with regard to the relationship between periodontal status and the long-term health status of patients with AD.

Objective 1: To determine the correlation between periodontal disease (PD) and the morbidity and mortality of Alzheimer's disease (AD)

To explore the correlation between PD and AD incidence using multifactorial logistic regression and the correlation between PD and mortality in AD patients using Cox's regression.

Objective 2: Identification of new genetic and non-genetic determinants

For this section, genetic and phenotypic correlations between PD and AD will be estimated to identify shared pathways associated with both diseases. We will also target specific genetic and other markers for candidate association analyses based on prior biological and clinical knowledge.

Objective 3: Critical assessment and causal inference

Mendelian randomisation analyses were performed and causal inferences were made for evidence with high confidence levels. Chain disequilibrium score (LDSC) regression and Mendelian randomisation (Mr) analyses allow further analysis of the relationship between PD and AD.

Combining the large data available from the UK Biobank with our analysis of epidemiological and molecular mechanisms will add to the current understanding of the pathogenesis and progression of PD and Alzheimer's disease. Our findings may also provide evidence for personalised disease prevention and management. This project is likely to extend beyond three years as the newly released data will require additional validation of our findings.