Explaining Disparities in Cognitive Function in Seniors

描述(由申请人提供)：这是第一次重新提交续签申请，以解决有关认知衰退原因的复杂网络的新的基本问题。巴尔的摩记忆研究是一项多层次纵向队列研究，研究登记时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1140名按性别、种族/民族和社会经济地位具有多样性的受试者，并跟踪其中943人(82.7%)进行第三次研究访问，平均2.5(0.2)年后。研究对象在三次研究访问中的每一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。我们有一套非常广泛的风险因素和潜在原因的衡量标准，包括血液、膝盖骨和胫骨中的铅、血汞、血清多氯联苯、血脂和同型半胱氨酸、整个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(即吸烟、酒精、饮食、体力活动)、社会网络、社会支持，以及与神经毒物、大脑功能或压力相关的8个基因中的10个基因多态性。最后，我们开发了一种严格的社区社会环境评估指标，称为社区心理社会危害(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，我们进行了许多新颖的观察。这些包括累积铅剂量与认知功能的下降和遗忘性轻度认知障碍有关；NPH与认知功能的下降有关；在研究访问期间总结四种唾液皮质醇测量的皮质醇指标与认知功能的下降有关(这种影响在那些携带APOE-e4等位基因的人中更严重)；NPH与皮质醇指标有关；NPH修改了胫骨铅与认知测试分数的关系。我们现在希望跟踪800名受试者进入第二阶段，在32个月内再进行两次研究访问，并对血管健康(CRP，sICAM-1)和HPA轴(六项唾液皮质醇测量)进行新的测量。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轴与“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.