Is Periodontitis Associated with Age-Related Cognitive Impairment? The Systematic Review, Confounders Assessment and Meta-Analysis of Clinical Studies

It has been suggested that molecular pathological mechanisms responsible for periodontitis can be linked with biochemical alterations in neurodegenerative disorders. Hypothetically, chronic systemic inflammation as a response to periodontitis plays a role in the etiology of cognitive impairment. This study aimed to determine whether periodontitis (PDS) is a risk factor for age-related cognitive impairment (ACI) based on evidence of clinical studies. A comprehensive, structured systematic review of existing data adhering to the Preferred Reporting Items for Systematic Review and Meta Analyses (PRISMA) guidelines was carried out. Five electronic databases, PubMed, Embase, Scopus, Web of Science, and Cochrane, were searched for key terms published in peer-reviewed journals until January 2021. The Newcastle–Ottawa scale was used to assess the quality of studies and risk of bias. The primary and residual confounders were explored and evaluated. A meta-analysis synthesizing quantitative data was carried out using a random-effects model. Seventeen clinical studies were identified, including 14 cohort, one cross-sectional, and two case-control studies. Study samples ranged from 85 to 262,349 subjects, with follow-up between 2 and 32 years, and age above 45 years, except for two studies. The findings of studies suggesting the PDS-ACI relationship revealed substantial differences in design and methods. A noticeable variation related to the treatment of confounders was observed. Quality assessment unveiled a moderate quality of evidence and risk of bias. The subgroups meta-analysis and pooled sensitivity analysis of results from seven eligible studies demonstrated overall that the presence of PDS is associated with an increased risk of incidence of cognitive impairment (OR = 1.36, 95% CI 1.03–1.79), particularly dementia (OR = 1.39, 95% CI 1.02–1.88) and Alzheimer’s disease (OR = 1.03 95% CI 0.98–1.07)). However, a considerable heterogeneity of synthesized data (I2 = 96%) and potential publication bias might affect obtained results. While there is a moderate statistical association between periodontitis and dementia, as well as Alzheimer’s disease, the risk of bias in the evidence prevents conclusions being drawn about the role of periodontitis as a risk factor for age-related cognitive impairment