Explaining Disparities in Cognitive Function in Seniors

解释老年人认知功能的差异

• 批准号: 7617592
• 负责人: BRIAN Seth SCHWARTZ
• 金额: $ 56.83万
• 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 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7617592
• 关键词: Accounting; Address; Adult; Age; Alcohols; Alleles; Anxiety; Apolipoprotein E; Baltimore; Behavioral; Blood; Blood Pressure; Blood Vessels; Brain; C-reactive protein; Cardiovascular system; Characteristics; Clinical; Cognition; Cognitive; Cohort Studies; Communities; Complex; Data Collection; Diet; Dimensions; Disease; Distal; Enrollment; Environmental Exposure; Ethnic Origin; Etiology; Evaluation; Funding; Future; Genes; Genetic; Genetic Polymorphism; Genotype; Grant; Habits; Health; High Density Lipoprotein Cholesterol; Homocysteine; Homocystine; Hydrocortisone; Hypertension; Impaired cognition; Intercellular adhesion molecule 1; Internet; Intervention; Interview; Knee bone; Knowledge; Lead; Lipids; Lung; Malignant Neoplasms; Manuscripts; Measures; Mediating; Mediation; Mediator of activation protein; Memory; Mercury; Metric; Modeling; Modification; Neighborhoods; Neurotoxins; Outcome; Participant; Performance; Persons; Phase; Physical activity; Polychlorinated Biphenyls; Prevalence; Proxy; Public Health; Race; Recording of previous events; Renal Glycosuria; Research; Risk Factors; Role; Salivary; Scientist; Serum; Social Conditions; Social Environment; Social Network; Social support; Socioeconomic Status; Stress; Study Subject; Testing; Time; Tobacco; Uncertainty; Visit; Work; aged; aging brain; cognitive function; cohort; depressive symptoms; functional status; hazard; hypothalamic-pituitary-adrenal axis; insight; interest; lead dose; longitudinal analysis; low density lipoprotein triglyceride; mild neurocognitive impairment; neurobehavioral test; novel; novel strategies; population based; prevent; psychosocial; sex; social; success; therapy development; tibia; trend

DESCRIPTION (provided by applicant): This is the first resubmission of renewal application to address new fundamental questions regarding the complex web of causes of cognitive decline. The Baltimore Memory Study is a multilevel longitudinal cohort study of the causes of cognitive decline in persons aged 50 to 70 years at enrollment. During Phase I we enrolled 1,140 subjects with diversity by sex, race/ethnicity, and SES and followed 943 (82.7%) of them to the third study visit an average (SD) of 2.5 (0.2) years later. Study subjects completed an extensive cognitive test battery at each of three study visits, and completed other health assessments and an extensive interview. We have a very broad set of measures of risk factors and potential causes, including lead in blood, patella, and tibia, blood mercury, serum PCBs, serum lipids and homocysteine, salivary cortisols across the study visit, detailed SES assessment, health-related habits (i.e., tobacco, alcohol, diet, physical activity), social networks, social support, and 10 genetic polymorphisms in 8 genes relevant to neurotoxicants, brain function, or stress. Finally, we developed a rigorous metric for assessment of the social environment in neighborhoods, termed the Neighborhood Psychosocial Hazards (NPH) scale, to evaluate how the neighborhood conditions can interact with other causes to impact cognitive function. In the first five years we have made a number of novel observations. These include that cumulative lead dose was associated with decrements in cognitive function and with amnestic mild cognitive impairment; NPH was associated with decrements in cognitive function; cortisol metrics that summarized four salivary cortisol measures across the study visit were associated with decrements in cognitive function (and this effect was worse among those with the APOE-e4 allele); NPH was associated with the cortisol metrics; and NPH modified relations of tibia lead with cognitive test scores. We now want to follow 800 subjects into Phase II, for two additional study visits over 32 months and new measures of vascular health (CRP, sICAM-1) and the HPA axis (six salivary cortisol measures). This will allow us to determine if the Phase I effects are persistent or progressive, and to examine relations among cognitive function, neurotoxicant exposures, the social environment, the HPA axis and "stress," vascular health, and aging, knowledge that will contribute to understanding etiology and mechanism and thus lead to public health and clinical interventions in the future.

描述（由申请人提供）：这是第一次重新提交续展申请，以解决有关认知能力下降的复杂原因网络的新基本问题。巴尔的摩记忆研究是一项多层次纵向队列研究，研究入组时 50 至 70 岁人群认知能力下降的原因。在第一阶段，我们招募了 1,140 名具有不同性别、种族/民族和社会经济地位的受试者，并对其中 943 名 (82.7%) 的受试者进行平均 (SD) 2.5 (0.2) 年后的第三次研究访视。研究对象在三次研究访问中每次都完成了广泛的认知测试，并完成了其他健康评估和广泛的访谈。我们对风险因素和潜在原因有一套非常广泛的衡量标准，包括血液、髌骨和胫骨中的铅、血汞、血清 PCB、血脂和同型半胱氨酸、整个研究访视期间的唾液皮质醇、详细的 SES 评估、健康相关的习惯（即烟草、酒精、饮食、体力活动）、社交网络、社会支持以及与神经毒物、大脑功能或压力相关的 8 个基因的 10 个遗传多态性。最后，我们开发了一个严格的社区社会环境评估指标，称为邻里心理社会危害（NPH）量表，以评估邻里条件如何与其他因素相互作用从而影响认知功能。在最初的五年里，我们做出了许多新颖的观察。其中包括累积铅剂量与认知功能下降和遗忘性轻度认知障碍有关； NPH 与认知功能下降有关；皮质醇指标总结了整个研究访问过程中四项唾液皮质醇测量值，与认知功能下降相关（这种效应在携带 APOE-e4 等位基因的人中更为严重）； NPH 与皮质醇指标相关； NPH 改变了胫骨导联与认知测试分数的关系。我们现在希望跟踪 800 名受试者进入 II 期，在 32 个月内进行两次额外的研究访问，并采用新的血管健康指标（CRP、sICAM-1）和 HPA 轴（六项唾液皮质醇指标）。这将使我们能够确定第一阶段的影响是持续的还是进行性的，并检查认知功能、神经毒物暴露、社会环境、HPA轴和“压力”、血管健康和衰老之间的关系，这些知识将有助于了解病因和机制，从而引导未来的公共卫生和临床干预。