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，特别是那些可能导致预防策略的因素，是至关重要的。硒是一种微量元素，被认为是通过维持更好的酶活性来抵抗自由基的防御剂。该应用是对中国农村65岁及以上老年人的纵向研究的延续，旨在证实或反驳长期低硒暴露与认知能力下降有关的假设。自2003年4月最初的项目开始以来，我们从中国四个农村县招募了2000名65岁及以上的老年人，收集了硒暴露、认知功能等信息的数据。我们的基线结果显示，低硒水平与认知功能下降有关。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有关。此外，还有一个有趣的发现，载脂蛋白E (APOE) 54等位基因携带者在指甲样本中测量的硒水平显着降低，即使两个基因型组在饮食硒摄入量上没有差异。该队列的数据还显示，未发现高血压的比例很高，血压升高与认知能力下降有关。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允许更好地表征慢性疾病和确定重要的心血管危险因素，从而使我们能够检查硒与认知能力下降的关联是独立的还是与认知能力下降和痴呆的其他潜在危险因素相互作用。我们还将研究硒和载脂蛋白E (APOE) 54等位基因在认知能力下降和痴呆中的潜在相互作用，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系。

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.