Air pollution and early signs of dementia

空气污染与痴呆症的早期症状

• 批准号: 10525882
• 负责人: Anke Huels
• 金额: $ 76.4万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 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/10525882
• 关键词: Address; Affect; African American; Age; Aging; Air Pollution; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid beta-42; Biological; Biological Markers; Blood; 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 (Brain); Hypertension; Impaired cognition; Impairment; Individual; Ischemia; Knowledge; Link; Longitudinal Studies; Measures; Mediating; Medical; Memory; Memory impairment; Mental Depression; Modification; Nerve Degeneration; Nervous system structure; 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; base; brain health; brain magnetic resonance imaging; cohort; comorbidity; dementia risk; design; executive function; fine particles; healthy aging; high risk; imaging genetics; 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

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 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造成空气污染的原因 失智。其次，他们倾向于依赖横截面分析。第三，他们不考虑痴呆症 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 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），也可能同时存在。具体来说，我们将利用来自四个方面的数据 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。这些纵向研究 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。每项研究都执行 详细的神经认知测试、AD 的标准脑脊液 (CSF) 生物标志物和脑容量 AD 和 VCI 的生物标志物，我们将指定高分辨率细颗粒环境空气污染浓度 （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 气相防锈。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） 以及脑部MRI测量的脑微血管缺血变化； 3）调查协会 空气污染与表观遗传加速衰老和痴呆相关 DNAm 模式之间的关系。关键的是，我们将 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。这项研究将 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。因此，我们 期望这项工作对该领域产生重要且持续的影响。