Explaining Disparities in Cognitive Function in Seniors

描述（由申请人提供）：这是第一次重新提交更新申请，以解决有关认知衰退原因的复杂网络的新基本问题。巴尔的摩记忆研究是一项针对50至70岁人群认知能力下降原因的多层次纵向队列研究。在第一阶段，我们招募了1140名不同性别、种族/民族和社会经济地位的受试者，其中943名（82.7%）在平均（SD） 2.5（0.2）年后进行了第三次研究访问。研究对象在每三次研究访问中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。我们有一套非常广泛的风险因素和潜在原因的测量方法，包括血液、髌骨和胫骨中的铅、血汞、血清多氯联苯、血清脂质和同型半胱氨酸、研究访问期间的唾液皮质醇、详细的SES评估、与健康相关的习惯（即烟草、酒精、饮食、体育活动）、社会网络、社会支持，以及与神经毒物、脑功能或压力相关的8个基因中的10个遗传多态性。最后，我们开发了一个严格的衡量标准，用于评估社区社会环境，称为社区社会心理危害（NPH）量表，以评估社区条件如何与其他原因相互作用，影响认知功能。在最初的五年里，我们做了一些新的观察。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；在整个研究访问期间，总结了四种唾液皮质醇测量值的皮质醇指标与认知功能下降有关（并且这种影响在携带APOE-e4等位基因的人中更严重）；NPH与皮质醇指标相关；NPH修正胫骨铅与认知测验成绩的关系。我们现在想跟踪800名受试者进入第二阶段，在32个月的时间里进行两次额外的研究访问，并进行新的血管健康测量（CRP, sICAM-1）和HPA轴（六项唾液皮质醇测量）。这将使我们能够确定I期效应是持续的还是渐进的，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，这些知识将有助于理解病因和机制，从而导致未来的公共卫生和临床干预。

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.