Selenium Levels and Cognitive Decline in Elderly Chinese

描述(申请人提供)：建议的研究项目是一项纵向流行病学研究，旨在证实或驳斥长期低硒暴露与认知能力下降相关的假说。硒是一种与抗氧化酶谷胱甘肽过氧化物酶活性有关的微量元素。它被认为是一种通过保持更好的酶活性来抵御自由基的防御剂。据报道，低硒与各种疾病指数(癌症、心血管疾病、生殖和新生儿健康以及哮喘)的风险增加之间存在关联。然而，关于硒与认知功能或阿尔茨海默病的有限研究并未得出明确的结论。在美国人口中研究长期硒暴露与认知能力下降之间的关系是困难的，因为美国人口是流动的，消费的食物是在世界不同地区生产和准备的。美国人群中的硒暴露也被与个人的社会经济和健康状况有关的补充剂严重混淆。与美国人口形成对比的是，中国农村人口异常稳定，大多数人一生都住在同一个村庄，消费当地种植的食物。这些村民服用膳食补充剂的情况也很罕见。最重要的是，中国科学家对硒作为一种环境制剂进行了广泛的研究。我们建议对大约2000名65岁及以上的中国农村居民进行纵向研究，其中一半来自低硒地区，另一半来自正常硒地区。这一农村人口的稳定性使人们可以估计终身接触环境中的硒。我们希望验证这一假设，即低硒暴露与更大的认知能力下降有关。我们还将确定APOE基因在该人群中的分布，并测试拥有APOE e4基因会增加认知能力下降风险的假设。我们将调查低硒与认知功能减退之间的关联强度是否受APOE基因的影响。此外，我们将尝试确定与这一人群中认知能力下降相关的其他风险因素。

DESCRIPTION (provided by applicant): The proposed research project is a longitudinal epidemiologic study aimed at confirming or refuting the hypothesis that long-term low selenium exposure is associated with greater cognitive decline. Selenium is a trace element associated with the activity of the antioxidant enzyme glutathione peroxidase. It is considered to be a defensive agent against free radicals through the maintenance of better enzyme activity. Associations between low selenium and increased risk in various disease indices (cancer, cardiovascular disease, reproduction and neonatal health, and asthma) have been reported. The limited studies on selenium and cognitive function or Alzheimer's disease, however, have not reached unequivocal conclusions. Studying the relationship between long-term selenium exposure and cognitive decline in the US population is difficult because the population is mobile and consumes foods that were produced and prepared in different areas of the world. Selenium exposure in the US population is also highly confounded by supplements that are related to the socio-economic and health status of the individuals. The rural Chinese population, in contrast to the US population, is unusually stable with most living in the same village throughout their entire life and consuming food that is locally grown. It is also rare for these villagers to take dietary supplements. Most importantly, selenium as an environmental agent has been studied extensively by Chinese scientists. We propose to conduct a longitudinal study on approximately 2000 rural Chinese age 65 and over with half of them from low selenium areas and the other half from normal selenium areas. The stability of this rural population allows for lifetime exposure estimates to environmental selenium. We hope to test the hypothesis that low selenium exposure is associated with greater cognitive decline. We will also determine the APOE genotype distribution in this population and test the hypothesis that possessing an APOE e4 increases the risk for cognitive decline. We will investigate whether the strength of the association between low selenium and cognitive decline is affected by APOE genotype. In addition we will try to identify other risk factors associated with cognitive decline in this population.