A cohort follow-up pilot study will be performed to develop preliminary data for a future R01 investigating the role of peripheral infections/inflammation in cognitive decline and brain damage. All patients will simultaneously be enrolled in other NIH funded studies of our collaborator to obtain long-term correlations. Inflammation is known to be involved in the pathogenesis of Alzheimer's disease (AD) and several lines of evidence point towards peripheral infection/inflammation as potential risks for AD. Our preliminary data has shown that subjects with periodontal inflammation have lower cognition compared to controls and this association was present among carriers of an inflammatory phenotype. It is our general hypothesis that peripheral sources of inflammation, with its added infectious/inflammatory burden, contribute to AD pathogenesis by contributing to progressive cognitive decline and brain damage. Since periodontal disease, a localized peripheral chronic infection affecting about 50% of people over 55 year of age, is characterized by a high gram negative pathogenic bacterial load often coupled with systemic inflammation, we will use periodontal disease as a model to test our hypothesis. We propose to follow- two groups each of 35 cognitively normal elderly subjects with and without periodontal disease (total 70 subjects). These subjects, recruited from NYU College of Dentistry (NYUCD) and Center for Brain Health (CBH), will be evaluated at 2-year follow-up for cognitive decline based on norm referenced tests and progressive brain atrophy assessed by MRI. The independent variables, which are the exposures for the brain, are: clinical periodontal disease, subgingival bacterial load (specific periodontal pathogens assayed by RT-PCR), and systemic inflammatory markers (plasma CRP, cytokines, chemokines). Regression analysis will determine the predictors of cognitive decline and brain atrophy. Based on our preliminary studies, we expect to identify inflammatory biomarkers whose use will lead to new clinical treatments to prevent cognitive decline and ultimately for AD.
Significant challenges in controlling AD are identifying risks that would prevent cognitive decline and brain damage. This project is designed to test if periodontal disease, a peripheral infection and inflammation contribute to brain atrophy an index of brain damage and cognitive decline in elderly.