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认识存在许多差距，这些首先，大多数空气污染暴露研究并没有区分造成空气污染的原因。其次，他们倾向于依赖横截面分析。第三，他们不考虑痴呆症。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。我们可以区分痴呆症的两种最常见原因，即阿尔茨海默病 (AD) 和血管性认知障碍（VCI），这也可能同时存在。具体来说，我们将利用四个方面的数据。大脑老化的各种纵向研究，包括来自亚特兰大和美国的 23,000 多名参与者乔治亚州跨越了广泛的年龄、社会经济地位和认知状态。关注未受影响或受影响最小的个体，因为研究这些个体可以为我们提供最好的帮助确定 AD 和 VCI 对整体认知的相对贡献的机会。详细的神经认知测试、AD 的标准脑脊液 (CSF) 生物标志物和脑容量 AD 和 VCI 的生物标志物，我们将指定高分辨率颗粒细环境空气污染浓度（PM2.5 及其组成部分）根据所有研究参与者当前和过去的居住地址向他们提供。利用这些丰富的数据可以测试空气污染与 AD 或 AD 不同方面之间的关联为了了解空气污染如何导致 AD、VCI 或两者兼而有之，我们将 1) 调查关联性。空气污染与以主观记忆抱怨、短期记忆为特征的 AD 指标之间的关系或基于神经认知测试、AD CSF 生物标志物阳性（即 Aβ42、总 Tau、和磷酸-Tau）和较小的海马体积；2）研究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）和通过脑 MRI 测量的脑微血管缺血变化；3) 研究关联性至关重要的是，我们将在空气污染与加速的表观遗传衰老和痴呆相关的 DNAm 模式之间进行研究。还评估性别、种族/民族、社会经济因素、遗传风险、抑郁症、心血管疾病本研究将改变空气污染与 AD 和 VCI 指标之间的关联。提供关于空气污染如何影响两个最常见原因的早期表现的生物学见解痴呆症（AD 和 VCI）以及修饰因素（例如性别和种族/民族）如何影响脆弱性。期望这项工作对该领域产生重要且持续的影响。