EXPLAINING DISPARITIES IN COGNITIVE FUNCTION IN SENIORS

解释老年人认知功能的差异

• 批准号: 6649833
• 负责人: BRIAN Seth SCHWARTZ
• 金额: $ 60.1万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6649833
• 关键词: African American; aging; apolipoprotein E; behavioral /social science research tag; blood pressure; caucasian American; clinical research; cognition disorders; disease /disorder proneness /risk; gastrointestinal absorption /transport; gene environment interaction; genotype; human middle age (35-64); human old age (65+); human subject; lead poisoning; longitudinal human study; neurotoxins; porphobilinogen synthase; racial /ethnic difference; social behavior; socioeconomics; sodium potassium exchanging ATPase; urban area; vitamin D receptors

DESCRIPTION (Taken from the Investigator's Abstract) Cognitive function (CF) is central to daily functioning and quality of life. The life course trajectory in CF is known to vary by race/ethnicity and socioeconomic status (SES), and this variation involves a complex causal web. Unpacking this causal web has important political, social, and public health implications, and provides a foundation for prevention and for ensuring social equity. However, we have only a rudimentary understanding of the factors that mediate these disparities in CF. The causal web is complex and involves such diverse and possibly interrelated domains as genetic, social, behavioral, environmental, contextual factors, and individual vascular health. The direct and indirect contributions of these diverse factors must be considered in trying to explain variation by race/ethnicity and SES, moving beyond the traditional but somewhat limiting exploration of "gene-environment interactions" by more broadly defining the underpinnings of these disparities. Ubiquitous potential causes of a decline in CF in older adults include lead exposure, apolipoprotein E (ApoE) genotype, vascular risk factors (i.e., blood pressure), and health-compromising behaviors (e.g., inactivity and smoking). Importantly, a number of genes known to differ by race/ethnicity appear to influence the toxicokinetics or toxicity of lead, including those for the 8-aminolevulinic dehydratase (ALAD), vitamin D receptor (VDR), Na/K ATPase (NKATP), and ApoE genes. Disparities in CF must be examined using next-generation data and methods that allow the modeling of the causal structure of these multiple domains, and to see how and to what extent social, behavioral, and contextual factors are important mediators and moderators along an extended causal pathway. Only by testing this more complete model, will it be possible to fully explicate the complex multilevel associations that pattern everyday life. The goal of this research is to understand the direct and indirect influences of lead absorption, four specific genes, individual social and behavioral factors, contextual factors, and blood pressure in accounting for the associations of race/ethnicity and SES with CF and cognitive decline. The investigators propose a five-year prospective study of 900 urban residents, aged 50 to 70 years, randomly selected from specific geographic areas with variation in race/ethnicity and SES. All study subjects will have three visits at 16-month intervals, with measurement of cognitive function, blood pressure, tibial lead, patellar lead, individual social and behavioral factors, current and past contextual factors, and ALAD, VDR, NKATP, and ApoE genotypes.

描述（摘自研究者摘要） 认知功能（CF）是日常功能和生活质量的核心。 已知CF的生命过程轨迹因种族/民族而异， 社会经济地位（SES），这种变化涉及一个复杂的因果网络。 解开这个因果网络对政治、社会和公共健康都有重要意义。 影响，并为预防和确保社会 股权 然而，我们对这些因素只有初步的了解， 在CF中调节这些差异。 因果网络是复杂的， 不同的和可能相互关联的领域，如遗传，社会，行为， 环境、背景因素和个体血管健康。 直接 必须考虑这些不同因素的间接贡献， 试图通过种族/民族和社会经济地位来解释差异，超越了 传统的但有些局限的“基因-环境”研究 通过更广泛地界定这些差异的基础，来确定“相互作用”。 老年人CF下降的普遍潜在原因包括铅 暴露、载脂蛋白E（ApoE）基因型、血管危险因素（即，血液 压力），以及危害健康的行为（例如，不活动和吸烟）。 重要的是，一些已知因种族/民族而异的基因似乎 影响铅的毒代动力学或毒性，包括铅的毒代动力学或毒性 8-氨基乙酰丙酸脱氢酶（ALAD），维生素D受体（VDR），Na/K ATP酶 （NKATP）和ApoE基因。 CF中的差异必须使用 下一代数据和方法，允许因果关系建模 这些多个领域的结构，并看看如何以及在多大程度上社会， 行为和情境因素是重要的中介和调节因素 沿着一条延伸的因果路径。 只有通过测试这个更完整的模型， 是否有可能完全解释复杂的多层次关联 that pattern模式everyday日常life. 这项研究的目的是了解 铅吸收的直接和间接影响，四个特定基因， 个体社会和行为因素、环境因素和血液 在解释种族/民族和SES与CF的关联方面的压力 和认知能力下降 研究人员提出了一项为期五年的前瞻性研究， 900名年龄在50至70岁之间的城市居民，随机从 种族/民族和社会经济地位不同的特定地理区域。 所有研究 受试者将以16个月的间隔进行三次访视，测量 认知功能、血压、胫骨电极导线、髌骨电极导线、个人 社会和行为因素，当前和过去的背景因素，以及ALAD， VDR、NKATP和ApoE基因型。