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: 10381292
• 负责人: James McCallum Noble
• 金额: $ 80.98万
• 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/10381292
• 关键词: 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; Bacteria; Biological Markers; Blood Vessels; Bone Marrow; Cerebrum; Clinical; Clinical Microbiology; Cognitive; Communities; Complex; Cytometry; Data; Dementia; Dental Plaque; Deposition; Diabetes Mellitus; Disease; Early Intervention; Education; Elderly; Elements; Enrollment; Epidemiology; Genetic; Health behavior; Image; Immune; Immunoglobulin G; Impaired cognition; Individual; Infection; Inflammatory; Inflammatory Response; Intervention; Knowledge; Language; Life Style; Link; Liquid substance; Liver; Longitudinal Studies; Longitudinal cohort; Longitudinal prospective study; Magnetic Resonance Imaging; Measures; Medical; Memory; Memory impairment; Microbial Biofilms; Microbiology; Minority Groups; Nerve Degeneration; Neurologic; Neuropsychological Tests; Neuropsychology; Obesity; Oral cavity; Oral health; Outcome; Participant; Pathologic; Pathway interactions; Periodontal Infection; Periodontitis; Periodontium; Peripheral; Persons; Phenotype; Plasma; Population; Prevalence; 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; base; clinical biomarkers; clinical examination; cohort; dementia risk; design; disadvantaged population; dysbiosis; epidemiology study; follow-up; immunosenescence; improved; innovation; literacy; metagenomic sequencing; microbial; modifiable risk; monocyte; multi-ethnic; multimodality; neuroimaging; next generation sequencing; novel; peripheral blood; rRNA Genes; 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.

牙周炎是一种由非生物膜引起的牙齿支持结构的感染，是一种常见的病因。 成人牙齿脱落的风险。它的患病率随着年龄的增长而显著增加，在少数族裔和 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有悬而未决的问题 ADRD的潜在致病途径的一部分，以及连接这两种情况的机制。 在这项建议中，我们打算进一步检验牙周炎是一种未被认识到的危险因素这一假设。 WHICAP口腔健康辅助研究参与者的事件认知障碍(R56 DE022568)。WHICAP是一个居住在曼哈顿北部的多种族纵向老年队列。自.以来 它在近30年前成立，每隔24个月对5000多名参与者进行连续评估 有医疗、社会和健康行为史，一般医学检查和神经心理测试。 对WHICAP数据的分析显著增加了我们对 社会人口学、遗传学、健康行为和生活方式、教育、识字和血管疾病 阿尔茨海默病与认知功能减退的关系。除了这些措施外，目前的WHICAP参与者 还在评估多种AD生物标志物，包括神经变性和血浆的多模式磁共振成像 AD的生物标志物包括淀粉样蛋白和磷酸-tau。 我们的目标是评估口腔健康辅助研究的大约750名参与者，他们仍在接受随访 (I)重复牙周检查，包括牙周炎的临床和微生物检查 (包括牙周菌斑样本的16S rRNA和元基因组测序)，以及(Ii)评估 外周血单核细胞图谱和全身炎症水平，以考察牙周炎对牙周炎的影响 8年期间的ADRD事件，并确定这两种情况之间的机械联系。 将全面的、纵向的牙周感染评估纳入WHICAP研究 提供了一个独特的机会来有效地检查牙周炎是如何与临床措施相关联的 事件AD/ADRD(包括神经学和神经心理学检查)以及成像和 两种疾病的血浆生物标志物证据。考虑到阿尔茨海默病和痴呆症之间存在无法解释的巨大差异 在老年人口和牙周炎既可预防又可治疗的事实中，确定 牙周炎作为认知障碍的潜在未被认识的危险因素，对公共健康具有重大意义 这意味着什么。