R01AG076015

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

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.

The Trustees Of Columbia University In The City Of New York

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

New York, New York 100323720 United States

Single Zip Code

Infectious Etiology of Alzheimer's Disease (R01 Clinical Trial Optional) (RFA-AG-21-034)

Amendment Since initial award the total obligations have increased 388% from $809,780 to $3,954,825.