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：
10216927
负责人：
CAROL Elaine FRANZ
金额：
$ 26.07万
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 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10216927
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 Process Public Health Radial Recording of previous events Risk Source Spin Labels 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 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。来自动物模型的新兴数据还表明，阿尔茨海默氏病的风险可能增加和与交通相关的空气污染物（陷阱）的相关痴呆症。陷阱的动物模型神经毒性的有力证据，但是现有的陷阱神经毒性影响对人脑衰老的研究已有重要知识差距：1）长期解决历史数据的很少； 2）迟到之前有关暴露效果的数据很少生活; 3）有限的认知数据，尤其是轻度认知障碍（MCI）或AD； 4）有限的神经影像学措施； 5）未检查潜在混杂的早期生活因素：6）对老年人的研究主要是在女性; 7）需要更好地理解基因环境的相互作用。项目2，建立在NIA- 资助的越南纵向时代双胞胎衰老研究（VETSA； R01 AG018386＆AG022381）是理想的选择解决这些差距。它包括Vetsa 1（n = 1291）的51-60岁男性双胞胎，Vetsa 2的男性双胞胎和55-66 （n = 1205）。 Vetsa是来自49个州的地理多样性队列，在陷阱中提供了很大的可变性接触。受试者在每个受试者中都有10-12个小时的神经心理学，社会心理和健康/医疗数据时间点； 545和447分别在Vetsa 1和2处具有结构性磁共振成像（MRI）。我们将通过收集和地理编码的居民历史数据回到1993年来解决差距1，并与环境暴露核心C，创建陷阱的累积指标。然后，我们将能够直接解决差距2-7。陷阱的特征是NO2（气态替代物）的估计环境水平， PM2.5的元素碳（EC）成分（柴油排气粒子的标记）和预测的源曲线 PM2.5。 VETSA受试者的年龄非常适合在晚期生命之前检查陷阱效应。我们检查了以下目的：目标1。评估陷阱对大脑结构/功能的影响：主要影响。我们预测陷阱暴露将与较高的广告相关大脑签名分数，脑灌注不足（平行鼠标项目4）和白质超强度。陷阱暴露将与较差的认知有关随着时间的流逝，功能和认知能力下降。目标2。评估陷阱对认知和脑老化：调解。我们将研究陷阱与认知特定度量之间的关联专注于情节记忆，执行功能和处理速度，以及通过特定的调解大脑措施。尚未在尚未在先前的研究。我们将检查媒体临时和额叶中灰质和白质的平均扩散率地区。目标3。检查基因环境（GE）相互作用。 3a）我们假设那个不良陷阱对大脑和认知能力下降的影响将随着APOE-ε4的函数而差异，而AD的多基因风险评分，炎症加工和TAU代谢/加工。 3B）我们将使用MZ内差分分析作为阐明遗传和环境影响如何串联的另一种方法。