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

牙周感染和阿尔茨海默病的纵向研究：口腔健康的 WHICAP 辅助研究

• 批准号: 10631203
• 负责人: James McCallum Noble
• 金额: $ 79.23万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10631203
• 关键词: Acceleration; Adult; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s Disease Pathway; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein; Amyloidosis; Ancillary Study; Antibodies; Atherosclerosis; Bacteremia; Bacteria; Biological; Biological Markers; Bone Marrow; Cerebrum; Clinical; Communities; Complex; Cytometry; Data; Dementia; Dental Plaque; Deposition; Diabetes Mellitus; Disease; Disparity population; Early Intervention; Education; Elderly; Elements; Enrollment; Epidemiology; Genes; Genetic; Health behavior; Height; Image; Immune; Immunoglobulin G; Impaired cognition; Individual; Infection; Inflammatory; Inflammatory Response; Intervention; Knowledge; Language; Life Style; Link; Liquid substance; Liver; Longitudinal Studies; Longitudinal cohort; Magnetic Resonance Imaging; Measures; Medical; Memory; Memory impairment; Microbial Biofilms; Microvascular Dysfunction; Minority Groups; Nerve Degeneration; Neurologic; Neuropsychological Tests; Neuropsychology; Obesity; Oral cavity; Oral health; Organ; Outcome; Participant; Pathologic; Pathway interactions; Periodontal Infection; Periodontitis; Periodontium; Peripheral; Persons; Phenotype; Plasma; Population; Prevalence; Protein Isoforms; Public Health; Recording of previous events; Ribosomal RNA; Risk Factors; Role; Sampling; Serology; Serum; Smoking; Social Behavior; Standardization; Stroke; Structure; Testing; Tooth Loss; Variant; Vascular Diseases; Vascular Endothelium; Visuospatial; Washington; Work; atherogenesis; clinical examination; cohort; comorbidity; dementia risk; dental biofilm; design; dysbiosis; epidemiology study; follow-up; immunosenescence; improved; inflammatory marker; innovation; literacy; longitudinal, prospective study; metagenomic sequencing; microbial; microbiome; microbiota; modifiable risk; monocyte; mortality; multi-ethnic; multimodality; neuroimaging; next generation sequencing; novel; peripheral blood; risk sharing; sociodemographics; systemic inflammatory response; tau Proteins; tau-1; therapy design; white matter

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.

牙周炎是由失调生物膜引起的牙齿支撑结构的感染和常见原因 成人牙齿脱落。随着年龄的增长，其患病率显着增加，并且在少数群体中尤其更高 弱势群体。流行病学证据表明，牙周炎与阿尔茨海默氏症有关 疾病（AD）和相关痴呆症（ADRD），但关于牙周炎的作用仍然存在 ADRD潜在的因果关系途径的一部分，以及连接这两种条件的机制。 在此提案中，我们打算进一步检验以下假设：牙周炎是无法识别的危险因素 WHICAP辅助研究的参与者的事件认知障碍（R56） DE022568）。 WHICAP是一个多种族的纵向人群，老年人居住在曼哈顿北部。自从 大约30年前，已有5,000多名参与者以24个月的间隔进行了连续评估 随着医学，社会和健康行为历史，一般体检和神经心理学检查。 WHICAP数据的分析显着提高了我们对复杂影响的了解 社会人口统计学，遗传学，健康行为和生活方式，教育，识字和血管疾病 事件广告的表达和认知能力下降。除了这些措施外，当前的WHICAP参与者 也正在评估多种AD生物标志物，包括神经变性和等离子体的多模式MRI 广告的生物标志物，包括淀粉样蛋白和磷酸化。 我们的目标是评估仍在跟踪的口腔健康辅助研究的大约750名参与者 （i）重复牙周检查，包括牙周炎的临床和微生物学测量 （包括16S rRNA和牙周斑块样品的宏基因组测序）和（ii）评估 外周单核细胞谱和全身感染水平，以检查牙周炎对 事件在8年内发生了事件，并确定两个条件之间的机械关联。 在WHICAP研究中纳入牙周感染的全面，纵向评估 提供了一个独特的机会，可以有效研究牙周炎如何与 事件AD/ADRD（包括神经心理学检查）以及成像和成像和 血浆生物标志物两种疾病的证据。鉴于AD和痴呆症有很大的无法解释的差异 在老年人口以及牙周炎既可以预防又可以治疗的事实中， 牙周炎是潜在的无法识别的认知障碍危险因素 含义。