EXPLAINING DISPARITIES IN COGNITIVE FUNCTION IN SENIORS

解释老年人认知功能的差异

• 批准号: 6372563
• 负责人: BRIAN Seth SCHWARTZ
• 金额: $ 60.27万
• 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/6372563
• 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（摘自研究者的摘要） 认知功能（CF）对于日常功能和生活质量至关重要。 众所周知，CF 的生命历程轨迹因种族/民族而异，并且 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于政治、社会和公共卫生具有重要意义 影响，并为预防和确保社会 公平。 然而，我们对影响其发展的因素还只有初步的了解。 调解 CF 中的这些差异。 因果网是复杂的，涉及这样的 多样化且可能相互关联的领域，如遗传、社会、行为、 环境、背景因素和个人血管健康。 直接的 必须考虑这些不同因素的间接贡献 试图解释种族/民族和社会经济地位的差异，超越 传统但有些限制的“基因-环境”探索 相互作用”，更广泛地定义这些差异的基础。 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）和危害健康的行为（例如不活动和吸烟）。 重要的是，许多已知因种族/民族而不同的基因似乎 影响铅的毒代动力学或毒性，包括那些 8-氨基乙酰丙酸脱水酶 (ALAD)、维生素 D 受体 (VDR)、Na/K ATP 酶 (NKATP) 和 ApoE 基因。 CF 的差异必须使用以下方法进行检查 允许对因果关系进行建模的下一代数据和方法 这些多个领域的结构，并了解社交方式和程度， 行为和情境因素是重要的中介因素和调节因素 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， 能否充分阐明复杂的多层次关联 那种日常生活模式。 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， 个人社会和行为因素、背景因素和血液 考虑种族/族裔和社会经济地位与 CF 之间的关联的压力 和认知能力下降。 研究人员提出了五年的展望 研究对象为 900 名 50 至 70 岁的城市居民，随机抽取 种族/民族和社会经济地位存在差异的特定地理区域。 所有学习 受试者将每隔 16 个月进行 3 次访视，测量 认知功能，血压，胫骨导联，髌骨导联，个体 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。