Urban Air Pollution and Pathological Brain Aging: A Nationwide Twin Study in Men

城市空气污染和病理性大脑老化：一项针对男性的全国性双胞胎研究

基本信息

批准号：
10456753
负责人：
CAROL Elaine FRANZ
金额：
$ 26.52万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10456753
关键词：
Address Adult Age Aging Air Air Pollutants Air Pollution Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk Animal Model Axon Back Blood Vessels Brain Carbon Cardiovascular Diseases Chronic Cognition Cognitive Cognitive aging Cognitive deficits Complement Consensus Data Demyelinations Deposition Diesel Exhaust Diffuse Diffusion Magnetic Resonance Imaging Early Diagnosis Early Intervention Early identification Elderly Environment Environmental Exposure Episodic memory Exposure to Funding Future Genetic Geography Health Heterogeneity Hour Human Impaired cognition Individual Inflammatory Intervention Studies Knowledge Lead Life Light Link Long-Term Effects Magnetic Resonance Imaging Measures Medial Mediating Mediation Mediator of activation protein Medical Memory Metabolism Methods Modeling Monozygotic twins Multi-Ethnic Study of Atherosclerosis Mus Mydriasis Nerve Degeneration Neural Pathways Neuropsychology Nitrogen Dioxide Parahippocampal Gyrus Pathologic Pathology Perforant Pathway Persons Process Public Health Radial Recording of previous events Risk Source Stress Structure System Thick Time Twin Multiple Birth Twin Studies United States National Institutes of Health Vietnam White Matter Hyperintensity Woman Work aging brain animal data apolipoprotein E-4 arterial spin labeling base cerebral hypoperfusion cognitive function cognitive task cohort early detection biomarkers entorhinal cortex executive function fine particles gene environment interaction gray matter indexing innovation male men middle age mild cognitive impairment neuroimaging neurotoxic neurotoxicity neurotoxicology particle polygenic risk score processing speed psychosocial response tau Proteins traffic-related air pollution vascular inflammation white matter

项目摘要

Substantial evidence indicates that exposure to outdoor air pollutants may accelerate cognitive aging. Emerging data from animal models also point to a possible increase in the risk of Alzheimer's disease (AD) and related dementias with exposure to traffic-related air pollutants (TRAP). Animal models of TRAP show strong evidence of neurotoxicity, but existing studies of neurotoxic effects of TRAP on human brain aging have important knowledge gaps: 1) little long-term address history data; 2) little data on exposure effects before late life; 3) limited data on cognition, particularly mild cognitive impairment (MCI) or AD; 4) limited neuroimaging measures; 5) no examination of potential confounding early-life factors: 6) studies of older adults mostly on women; and 7) need for better understanding of gene-environment interactions. Project 2, built on the NIA- funded longitudinal Vietnam Era Twin Study of Aging (VETSA; R01 AG018386 & AG022381), is ideal for addressing these gaps. It includes male twins ages 51-60 at VETSA 1 (n=1291) and 55-66 at VETSA 2 (n=1205). VETSA is a geographically-diverse cohort from 49 states, offering great variability in TRAP exposure. Subjects have 10-12 hours of neuropsychological, psychosocial, and health/medical data at each timepoint; 545 and 447 have structural magnetic resonance imaging (MRI) at VETSA 1 and 2, respectively. We will address gap #1 by collecting and geocoding residential history data back to 1993, and in conjunction with Environmental Exposures Core C, create cumulative indices of TRAP. We will then be able to directly address gaps 2-7. TRAP will be characterized by the estimated ambient levels of NO2 (a gaseous surrogate), elemental carbon (EC) component of PM2.5 (a marker of diesel exhaust particle), and predicted source profiles of PM2.5. The age of VETSA subjects is ideal for examining TRAP effects before late life. We examine the following aims: Aim 1. Assess TRAP effects on brain structure/function: Main effects. We predict TRAP exposure will be associated with higher AD-related brain signature scores, cerebral hypoperfusion (paralleling Mouse Project 4), and white matter hyperintensities. TRAP exposure will be associated with poorer cognitive function and greater cognitive decline over time. Aim 2. Assess the impact of TRAP on cognitive and brain aging: Mediation. We will examine associations between TRAP and specific measures of cognition with a focus on episodic memory, executive function, and processing speed, as well its mediation by specific brain measures. Diffusion tensor imaging (DTI) indices of brain microstructure have not been examined in prior studies. We will examine mean diffusivity in both grey and white matter in medial temporal and frontal regions. Aim 3. Examine gene-environment (GE) interaction. 3a) We hypothesize that adverse TRAP effects on brain and cognitive decline will differ as a function of APOE-ε4, and polygenic risk scores for AD, inflammatory processing, and tau metabolism/processing. 3b) We will use MZ within-pair difference analysis as another approach to shed light on how genetic and environmental influences work in tandem.

大量证据表明，接触室外空气污染物可能会加速认知衰老。来自动物模型的新数据也表明，阿尔茨海默病 (AD) 的风险可能会增加 TRAP 动物模型显示，与接触交通相关空气污染物（TRAP）有关的痴呆症。神经毒性的有力证据，但 TRAP 对人类大脑衰老的神经毒性作用的现有研究重要的知识差距：1）长期地址历史数据很少；2）关于后期暴露影响的数据很少；生活；3) 认知数据有限，特别是轻度认知障碍 (MCI) 或 AD 4) 神经影像学有限；措施；5) 没有检查潜在的早期生活混杂因素：6) 对老年人的研究主要针对女性；7) 需要更好地了解基于 NIA 的基因-环境相互作用。资助的纵向越南时代孪生衰老研究（VETSA；R01 AG018386 和 AG022381），非常适合它包括 VETSA 1 中年龄为 51-60 岁的男性双胞胎 (n=1291) 和 VETSA 2 中年龄为 55-66 岁的男性双胞胎。 (n=1205) VETSA 是来自 49 个州的地理多样化群体，TRAP 的差异很大。受试者每次都有 10-12 小时的神经心理学、心理社会和健康/医学数据。时间点；545 和 447 分别在 VETSA 1 和 2 进行结构磁共振成像 (MRI)。将通过收集 1993 年以来的居住历史数据并进行地理编码来解决第一个问题环境暴露核心 C，创建 TRAP 累积指数，然后我们将能够直接解决。间隙 2-7 的特征是 NO2（气体替代物）的估计环境水平， PM2.5 的元素碳 (EC) 成分（柴油机尾气颗粒的标记）以及预测的来源概况 PM2.5 受试者的年龄是检查晚年之前的 TRAP 影响的理想年龄。以下目标：目标 1. 评估 TRAP 对大脑结构/功能的影响：我们预测 TRAP 的主要影响。暴露与较高的 AD 相关脑特征评分、脑灌注不足有关（平行小鼠项目 4) 和白质高强度 TRAP 暴露与认知能力较差有关。目标 2. 评估 TRAP 对认知和认知功能的影响。大脑老化：我们将研究 TRAP 与特定认知测量之间的关联。重点关注情景记忆、执行功能和处理速度，以及特定的中介作用大脑微结构的扩散张量成像（DTI）指数尚未进行检查。我们将检查内侧颞叶和额叶灰质和白质的平均扩散率。目标 3. 检查基因-环境 (GE) 相互作用 3a) 我们冒险采用不利的 TRAP。对大脑和认知能力下降的影响将根据 APOE-ε4 和 AD 的多基因风险评分而有所不同，炎症处理和 tau 代谢/处理 3b) 我们将使用 MZ 配对内差异分析。作为阐明遗传和环境影响如何协同作用的另一种方法。