Periodontal disease and Alzheimer's disease: A systematic review

BackgroundPeriodontitis is a host-mediated inflammatory disease of microbial origin that results in the loss of periodontal attachment. Its effects are not limited to the oral cavity, as association with systemic diseases, including Alzheimer's disease (AD), has been widely reported.ObjectiveTo evaluate the evidence regarding the potential relationship between periodontitis and AD through a systematic review.MethodsA bibliographic search was conducted in PubMed, Scopus, and WOS. Studies published within the last five years evaluating the biological association between both diseases were selected. The methodological quality and risk of bias of the included studies were assessed using the NOS and ROBINS-I tool, according to the study design.ResultsEleven studies were included. Eight studies analyzed biological samples obtained from brain tissue, blood/serum, saliva, gingival crevicular fluid, and cerebrospinal fluid. Patients with AD exhibited higher levels of periodontopathogenic bacteria, such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella intermedia, and an association between bacterial load and systemic inflammatory markers. Although most studies reported an association between periodontitis and AD, the findings were not consistent across studies, as some failed to identify statistically significant differences. Periodontal treatment was associated with a reduction in the AD Score, a neuroimaging surrogate marker of preclinical AD, whereas no effect was observed on brain age gap.ConclusionsEvidence suggests a possible association between periodontitis and AD through inflammatory and neurodegenerative mechanisms. Methodological limitations and study heterogeneity preclude establishing causality, underscoring the need for longitudinal studies and alternative methodological approaches.