Epidemiologic, imaging and pathological studies of the role of blood pressure variability in dementia etiology

血压变异性在痴呆病因中的作用的流行病学、影像学和病理学研究

基本信息

批准号：
10456714
负责人：
Yuan Ma
金额：
$ 13万
依托单位：
HARVARD SCHOOL OF PUBLIC HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10456714
关键词：
Address Aging Alzheimer disease prevention Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk Amyloid beta-Protein Atherosclerosis Risk in Communities Autopsy Biological Blood Pressure Blood Vessels Cerebral small vessel disease Cerebrovascular Disorders Cities Clinical Cohort Studies Coronary heart disease Data Data Sources Dementia Deposition Disease Elderly Epidemiologic Methods Epidemiology Etiology Europe Family Framingham Heart Study Future Goals Heterogeneity Hypertension Image Individual Investigation Kidney Diseases Knowledge Life Expectancy Link Longitudinal cohort Measurement Measures Mediating Mediation Medical Medicine Memory Methods Modification Participant Pathologic Pathology Pathway interactions Persons Phase Positioning Attribute Positron-Emission Tomography Posture Prevention Preventive Medicine Prospective cohort study Reporting Research Personnel Risk Role Sex Differences Source Standardization Stroke Testing Training Visit White Matter Hyperintensity Work blood pressure control blood pressure elevation blood pressure variability brain magnetic resonance imaging cardiovascular disorder risk career cerebral microbleeds clinical practice clinical translation cohort dementia risk economic cost epidemiologic data epidemiology study experience insight mortality mortality risk neuroimaging neuropathology novel novel marker post-doctoral training religious order study risk stratification skills social tau Proteins vascular risk factor

项目摘要

Application Number: 1 K99 AG071742-01 PI: MA, YUAN Modified Project Summary/Abstract Section Epidemiologic, imaging and pathological studies of the role of blood pressure variability in the etiology of Alzheimer's disease and related dementias Project Summary The etiology of Alzheimer's disease and related dementias (ADRD; hereinafter, used interchangeably with dementia) in older adults is multifactorial, and vascular risk factors, especially hypertension, are major modifiable contributors. However, the relationship between blood pressure (BP) and dementia is far from clear. Increased BP variability over different periods has been linked to cardiovascular disease and mortality risk independent of static BP levels. Emerging evidence has also suggested BP variability as a novel risk factor for Alzheimer's disease and related dementias. But the clinical translation of BP variability for the risk stratification and prevention of Alzheimer's disease and related dementias has been hampered by the lack of standards for assessing BP variability and the lack of knowledge on the underlying mechanisms. The goals of this project are to 1) comprehensively quantify the epidemiological relationship between BP variability and Alzheimer's disease and related dementias and 2) identify the causal pathways linking BP variability to Alzheimer's disease and related dementias. To accomplish these, the data from 6 prospective cohort studies across the US and Europe will be analyzed: the Framingham Heart Study, the Rotterdam Study, the Three-City Study, the Atherosclerosis Risk in Communities Study, and the Rush Religious Orders Study and Memory and Aging Project. In Aim 1, the relationship between 3 types of BP variability (visit-to-visit variability, beat-to-beat variability, and postural variability) and the risk of Alzheimer's disease and related dementias will be quantified by pooling individual data (n~31,274) from the above 6 cohort studies using consistent approaches. Aims 2 and 3 will further investigate the mechanisms underlying these epidemiologic relationships. Specifically, in Aim 2, the extent to which cerebral small vessel disease mediates the relationship between BP variability and the risk of Alzheimer's disease and related dementias among participants with brain MRI data will be determined using causal mediation analysis. Aim 3 (R00 phase) extends the investigation to Alzheimer’s disease (AD) pathology using neuropathology and neuroimaging data, where the interplay between BP variability, vascular pathology, AD pathology and the risk of Alzheimer's disease and related dementias will be characterized. This K99 project will enhance the PI’s prior training in medicine and epidemiology and further expand her expertise in 1) causal inference methods, 2) employing neuroimaging and neuropathology data, and 3) incorporating clinical and mechanistic relevance in epidemiological studies. This project will enable the PI to establish herself as an independent researcher using advanced epidemiological methods and interdisciplinary skills to make significant contributions to the prevention of Alzheimer's disease and related dementias.

申请编号：1 K99 AG071742-01 PI：MA，Yuan 修改的项目摘要/摘要部分血压变异性在阿尔茨海默氏病和相关痴呆症的病因中的作用的流行病学，成像和病理研究项目摘要老年人中，阿尔茨海默氏病和相关痴呆症的病因（ADRD；以下简称与痴呆症互换）是多因素的，而血管危险因素，尤其是高血压因素，是主要的可修改贡献者。但是，血压（BP）和痴呆症之间的关系远非明显。在不同时期内的BP变异性增加与心血管疾病和死亡率风险有关，而与静态BP水平无关。新兴证据还表明，BP变异性是阿尔茨海默氏病和相关痴呆症的新型危险因素。但是，由于缺乏评估BP变异性的标准以及对基本机制缺乏知识的缺乏标准，BP变异性的临床变异性在风险分层和预防阿尔茨海默氏病和相关痴呆症的临床翻译中受到了阻碍。该项目的目标是1）全面量化BP变异性与阿尔茨海默氏病与相关痴呆症之间的流行病学关系，以及2）确定将BP变异性与阿尔茨海默氏病和相关痴呆症联系起来的因果途径。为了实现这些作用，将分析来自美国和欧洲的6项前瞻性队列研究的数据：弗雷明汉心脏研究，鹿特丹研究，三城市研究，社区研究中的动脉粥样硬化风险以及Rush宗教秩序的研究以及记忆和记忆和衰老项目。在AIM 1中，将通过汇总以上6个队列的研究使用一致的方法来量化3种类型的BP变异性（访问到访问性变异性，Beat-to-beat变异性和姿势变异性）与阿尔茨海默氏病和相关痴呆症的风险之间的关系。目标2和3将进一步研究这些流行病学关系的基础机制。具体而言，在目标2中，将使用催化中介分析确定脑小血管疾病介导BP变异性与患有大脑MRI数据的相关痴呆症的风险之间的关系的程度。 AIM 3（R00阶段）使用神经病理学和神经影像学数据将投资扩展到阿尔茨海默氏病（AD）病理学，其中BP变异性，血管病理学，AD病理学和阿尔茨海默氏病和相关痴呆症的风险之间的相互作用将得到表征。该K99项目将增强PI先前在医学和流行病学方面的培训，并进一步扩大她在1）灾难性推理方法中的专业知识，2）使用神经成像和神经病理学数据，以及3）在流行病学研究中纳入临床和机械相关性。该项目将使PI使用先进的流行病学方法和跨学科技能确立自己的独立研究人员，从而为预防阿尔茨海默氏病和相关痴呆症做出重大贡献。