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