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Air pollution and early signs of dementia

空气污染与痴呆症的早期症状

基本信息

批准号：
10709878
负责人：
Anke Huels
金额：
$ 76.09万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-30 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10709878
关键词：
Acceleration Address Affect African American Age Aging Air Pollution Alzheimer&apos s Disease Alzheimer&apos s disease risk Alzheimer’s disease biomarker Amyloid beta-42 Biological Biological Markers Blood Blood Vessels Brain Cardiovascular Diseases Cerebrospinal Fluid Cerebrovascular Disorders Cerebrum Characteristics Chronic Disease Clinical Cognition Cognitive Confounding Factors (Epidemiology)Cross-Sectional Studies DNA Methylation Data Dementia Diabetes Mellitus Elderly Epigenetic Process Ethnic Origin Exposure to Female Genetic Genetic Risk Health Hippocampus Hypertension Image Impaired cognition Impairment Individual Ischemia Knowledge Link Longitudinal Studies Measures Mediating Medical Memory Memory impairment Mental Depression Modification Nerve Degeneration Nervous System Observational Study Olfactory Nerve Participant Persons Psychological Factors Race Research Resolution Risk Risk Factors Role Short-Term Memory Socioeconomic Factors Socioeconomic Status Stress Symptoms Testing United States Environmental Protection Agency Vascular Cognitive Impairment Work aging brain ambient air pollution apolipoprotein E-4 brain health brain magnetic resonance imaging cohort comorbidity dementia risk design executive function fine particles healthy aging high risk insight language impairment low socioeconomic status methylation pattern modifiable risk neighborhood disadvantage neurocognitive test programs racial diversity recruit sex social systemic inflammatory response tau Proteins tau-1

项目摘要

Air pollution exposure is a critical health risk factor for many chronic illnesses and has been linked to dementia. However, there are a number of gaps in our knowledge of how air pollution contributes to dementia, and these are the focus of our proposal. First, most air pollution exposure studies do not differentiate between causes of dementia. Second, they tend to rely on cross-sectional analyses. Third, they do not consider dementia biomarkers. To address those issues, we chose to focus on longitudinal studies of aging and brain health where we can distinguish among two of the most common causes of dementia, i.e., Alzheimer's disease (AD) and vascular cognitive impairment (VCI), which may also co-exist. Specifically, we will leverage data from four diverse longitudinal studies of brain aging including more than 23,000 participants from metro-Atlanta and Georgia spanning a wide range of age, socioeconomic status, and cognitive status. These longitudinal studies focus on unaffected or minimally affected individuals since studying those individuals affords us the best chance of determining the relative contribution of AD and VCI to overall cognition. Each study performs detailed neurocognitive testing, standard cerebrospinal fluid (CSF) biomarkers of AD and brain volumetric biomarkers of AD and VCI and we will assign high-resolution fine particle ambient air pollution concentrations (PM2.5 and its components) to all study participants based on their current and past residential addresses. Leveraging these rich data allows to test for association between air pollution and different facets of AD- or VCI. To understand how air pollution contributes to AD, VCI, or both, we will 1) investigate associations between air pollution and indicators of AD characterized by subjective memory complaints, short-term memory or language impairment based on neurocognitive testing, positive AD CSF biomarkers (i.e., Aβ42, total-Tau, and phospho-Tau) and smaller hippocampal volumes; 2) investigate associations between air pollution and indicators of VCI characterized by impairment in the executive function (measured by neurocognitive testing) and cerebral microvascular ischemia changes measured by brain MRI; and 3) investigate associations between air pollution and accelerated epigenetic aging and dementia-related DNAm patterns. Critically, we will also evaluate how sex, race/ethnicity, socioeconomic factors, genetic risk, depression, cardiovascular disease and diabetes modify the associations between air pollution and indicators of AD and VCI. This study will provide biological insights of how air pollution affects early manifestations of the two most common causes of dementia (AD and VCI) and how modifiers (e.g., sex and race/ethnicity) affect vulnerability. Therefore, we expect this work to have an important and sustained impact on the field.

空气污染暴露是许多慢性疾病的关键健康风险因素，并与痴呆症有关。然而，我们对空气污染如何导致痴呆症的了解还存在许多差距，而这些是我们提案的重点。首先，大多数空气污染暴露研究没有区分痴呆其次，他们倾向于依赖横截面分析。第三，他们不认为痴呆生物标志物。为了解决这些问题，我们选择专注于衰老和大脑健康的纵向研究在那里我们可以区分两种最常见的痴呆症原因，即，阿尔茨海默病（AD）和血管性认知障碍（VCI），这也可能共存。具体来说，我们将利用四个方面的数据，对大脑老化的各种纵向研究，包括来自亚特兰大大都会的23,000多名参与者，格鲁吉亚跨越广泛的年龄，社会经济地位，认知状态。这些纵向研究关注未受影响或影响最小的个体，因为研究这些个体可以为我们提供最好的确定AD和VCI对整体认知的相对贡献的机会。每项研究均进行详细的神经认知测试、AD的标准脑脊液（CSF）生物标志物和脑体积 AD和VCI的生物标志物，我们将分配高分辨率的细颗粒环境空气污染浓度（PM2.5及其组成部分），以所有研究参与者的当前和过去的居住地址为基础。利用这些丰富的数据可以测试空气污染与AD不同方面之间的关联， VCI。为了了解空气污染如何导致AD、VCI或两者，我们将1）调查空气污染和AD指标之间的关系，其特征在于主观记忆投诉，短期记忆或基于神经认知测试的语言障碍，阳性AD CSF生物标志物（即，Aβ42，总-Tau，和磷酸化-Tau）和较小的海马体积; 2）调查空气污染与以执行功能受损为特征的VCI指标（通过神经认知测试测量）和脑MRI测量的脑微血管缺血变化; 3）研究相关性空气污染和加速的表观遗传衰老以及与痴呆症相关的DNA模式之间的关系。关键是，我们会还评估性别、种族/民族、社会经济因素、遗传风险、抑郁症、心血管疾病和糖尿病改变了空气污染与AD和VCI指标之间的关联。本研究将提供了空气污染如何影响两个最常见的原因的早期表现的生物学见解，痴呆（AD和VCI）和如何修饰（例如，性别和种族/族裔）影响脆弱性。所以我们预计这项工作将对实地产生重要和持续的影响。