Selenium, other risk factors and cognitive decline in rural elderly Chinese

描述（由主要研究者提供）：识别与认知能力下降相关的风险或保护因素，尤其是可能导致预防策略的因素，至关重要。硒是一种微量元素，被认为是通过维持更好的酶活性来对抗自由基的防御剂。拟议的应用是对中国农村65岁或以上老年人的合作纵向研究的继续，旨在证实或反驳长期低硒暴露与更大的认知能力下降相关的假设。自2003年4月启动最初的项目以来，我们从中国四个农村县招募了2000名65岁及以上的个体，并收集了硒暴露、认知功能和其他信息的数据。我们的基线结果表明，低硒水平与较低的认知功能有关。我们还报道了较高的血浆钙水平与较高的认知评分相关。另一方面，较高的血浆镉和铜水平与较低的认知得分相关。此外，有一个有趣的发现，载脂蛋白E（APOE）54等位基因携带者在指甲样本中测得的硒水平显着较低，即使两个基因型组在硒的饮食摄入量上没有差异。来自该队列的数据还显示，有很高比例的未被发现的高血压和更高的血压测量与更大的认知能力下降相关。我们建议再进行两次认知功能评估，并收集所有研究参与者的血液样本，以获得生物标志物测量，包括脂质、同型半胱氨酸、胰岛素、葡萄糖、白细胞介素-6水平以及其他微量元素水平，包括钙、镉和铜。这些生物标志物测量将使我们能够更好地描述该队列中的慢性疾病并确定重要的心血管风险因素，从而使我们能够检查硒与认知能力下降的相关性是独立的还是与认知能力下降和痴呆的其他潜在风险因素相互作用。我们还将研究硒和载脂蛋白E（APOE）54等位基因对认知能力下降和痴呆的潜在相互作用，并确定血液样本中测量的其他微量元素水平与认知能力下降之间的关联。 公共卫生相关性： 拟议的应用是一项纵向流行病学研究的继续，旨在证实或驳斥长期低硒暴露与更大的认知能力下降和痴呆症风险增加相关的假设。硒暴露是一个很容易通过改变饮食习惯或补充剂来改变的因素。我们的假设如果得到证实，可以提供第一个证据支持长期硒作为认知能力下降的保护剂。对认知能力下降采取预防措施，即使是适度的措施，也可以对公共卫生产生重大影响，减少认知能力受损的流行病例，从而降低治疗和照顾受损者的费用。最重要的是，认知能力下降的预防措施可以延长健康老龄化的状态，并保持美国和世界各地许多老年人的生活质量。

DESCRIPTION (provided by principal investigator): The identification of risk or protective factors associated with cognitive decline, especially ones that may lead to prevention strategy, is critically important. Selenium is a trace element that is considered a defensive agent against free radicals through the maintenance of better enzyme activity. The proposed application is the continuation of a collaborative longitudinal study of rural elderly Chinese age 65 or older aimed at confirming or refuting the hypothesis that long-term low selenium exposure is associated with greater cognitive decline. Since the start of the original project in April 2003, we have enrolled 2000 individuals age 65 and older from four rural Chinese counties and collected data on selenium exposure, cognitive function and other information. Our baseline results showed that low selenium levels were associated with lower cognitive function. We also reported that higher plasma calcium level was associated with higher cognitive scores. Higher plasma cadmium and copper levels, on the other hand, were associated with lower cognitive scores. In addition, there is an intrigue finding that apolipoprotein E (APOE) 54 allele carriers had significantly lower selenium levels measured in nail samples even though the two genotype groups did not differ on dietary intake of selenium. Data from this cohort also reveals that there is a high proportion of undetected hypertension and higher blood pressure measures were associated with greater cognitive decline. We propose to conduct two more evaluations of cognitive function and to collect blood samples from all study participants in order to obtain biomarker measures including lipids, homocysteine, insulin, glucose, interleukin-6 levels as well as other trace element levels including calcium, cadmium and copper. These biomarker measures will allow better characterization of chronic medical conditions and ascertainment of important cardiovascular risk factors in this cohort, thus enabling us to examine whether selenium's association with cognitive decline is independent or interactive with other potential risk factors for cognitive decline and dementia. We will also examine the potential interaction between selenium and apolipoprotein E (APOE) 54 allele on cognitive decline and dementia and determine the association between other trace element levels measured in blood samples and cognitive decline. PUBLIC HEALTH RELEVANCE: The proposed application is the continuation of a longitudinal epidemiologic study aimed at confirming or refuting the hypothesis that long-term low selenium exposure is associated with greater cognitive decline and greater risk for dementia. Selenium exposure is a factor that is easily modifiable by changing dietary habits or through supplements. Our hypotheses, if confirmed, can provide the first evidence supporting long-term selenium as a protective agent against cognitive decline. A preventive measure on cognitive decline, even moderate, can have a significant impact on public health by reducing prevalent cases of cognitive impairment, thus reducing the cost of treating and caring for the impaired. Most importantly, preventive measures for cognitive decline can prolong the state of healthy aging and maintain the quality of life for many elderly individuals in the U.S. and around the world.