A Longitudinal Study of Periodontal Infections and Alzheimer's Disease: The WHICAP Ancillary Study of Oral Health

点击翻译按钮获取中文摘要

Periodontitis is an infection of the tooth-supporting structures elicited by dysbiotic biofilms and a common cause of tooth loss in adults. Its prevalence increases significantly with age and is particularly elevated in minority and disadvantaged populations. Epidemiologic evidence suggests that periodontitis is associated with Alzheimer’s Disease (AD) and related dementias (ADRD), but open questions remain regarding the role of periodontitis as part of a potential causative pathway for ADRD, and the mechanisms linking the two conditions. In this proposal, we intend to further test the hypothesis that periodontitis is an unrecognized risk factor for incident cognitive impairment among the participants in the WHICAP Ancillary Study of Oral Health (R56 DE022568). WHICAP is a multi-ethnic longitudinal cohort of aging elderly residing in northern Manhattan. Since its inception nearly 30 years ago, more than 5,000 participants have been serially assessed in 24-month intervals with medical, social, and health behavior histories, general medical exams, and neuropsychological testing. Analyses of WHICAP data have markedly increased our knowledge of the complex influence of sociodemographics, genetics, health behavior and lifestyle, education, literacy, and vascular disease in the expression of incident AD and cognitive decline. In addition to these measures, current WHICAP participants are also being assessed for multiple AD biomarkers including multimodal MRI for neurodegeneration and plasma biomarkers for AD including amyloid and phospho-tau. We aim to assess approximately 750 participants of the Ancillary Study of Oral Health who are still followed up to (i) a repeat periodontal examination, encompassing clinical and microbiological measures of periodontitis (including 16S rRNA and metagenomic sequencing of periodontal plaque samples), and (ii) an assessment of peripheral monocyte profiles and levels of systemic inflammation, to examine the effect of periodontitis on incident ADRD over an 8-year period, and to identify mechanistic associations between the two conditions. Incorporating comprehensive, longitudinal assessments of periodontal infection within the WHICAP study provides a unique opportunity to efficiently examine how periodontitis associates with clinical measures of incident AD/ADRD (including neurologic and neuropsychological examinations) as well as with imaging and plasma biomarker evidence of both diseases. Given the substantial unexplained variance in AD and dementia in the elderly population and the fact that periodontitis is both preventable and treatable, identification of periodontitis as a potential unrecognized risk factor for cognitive impairment has significant public health implications.