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

牙周炎是一种由生物膜引起的牙齿支持结构的感染， 成年人的牙齿脱落。其患病率随着年龄的增长而显著增加，在少数民族和 弱势群体。流行病学证据表明牙周炎与阿尔茨海默病有关 疾病（AD）和相关痴呆（ADRD），但关于牙周炎作为 ADRD的潜在致病途径的一部分，以及连接这两种情况的机制。 在这个建议中，我们打算进一步验证牙周炎是一个未被认识到的危险因素的假设， WHICAP口腔健康辅助研究（R56）参与者中的偶发性认知障碍 DE022568）。WHICAP是居住在北方曼哈顿的老年人的多种族纵向队列。以来 该项目于近30年前启动，每隔24个月对5,000多名参与者进行一系列评估 医学，社会和健康行为史，一般医学检查和神经心理学测试。 对WHICAP数据的分析大大增加了我们对以下因素的复杂影响的认识： 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 AD和认知能力下降的表现。除了这些措施外，目前的WHICAP参与者 也正在评估多种AD生物标志物，包括神经变性和血浆 AD的生物标志物包括淀粉样蛋白和磷酸化tau。 我们的目标是评估大约750名参与口腔健康辅助研究的参与者，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测量 （包括牙周菌斑样本的16 S rRNA和宏基因组测序），以及（ii）评估 外周血单核细胞谱和全身炎症水平，以检查牙周炎对 事件ADRD超过8年的时间，并确定这两个条件之间的机械关联。 在WHICAP研究中对牙周感染进行全面的纵向评估 提供了一个独特的机会，有效地检查牙周炎如何与临床措施， 事件AD/ADRD（包括神经学和神经心理学检查）以及影像学检查， 两种疾病的血浆生物标志物证据。考虑到AD和痴呆症之间的巨大差异 在老年人群中，牙周炎是可预防和可治疗的， 牙周炎作为认知障碍的潜在未被认识的危险因素， 影响

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.