Serum Uric Acid as a Biomarker of Cognitive and Functional Decline in Late Life

血清尿酸作为晚年认知和功能下降的生物标志物

• 批准号: 7706235
• 负责人: Tracy Dawn Vannorsdall
• 金额: $ 7.22万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7706235
• 关键词: Adult; Age; Aging; Alcohol abuse; Attention; Authorization documentation; Biological Markers; Blood; Brain; Cardiovascular system; Cerebral Ischemia; Cerebrum; Clinical Trials; Cognition; Cognitive; Communities; Data; Data Analyses; Development; Elderly; Elderly woman; Goals; Grant; Health; Hypertension; Impaired cognition; Individual Differences; Injury; Investigation; Measures; Mediating; Normal Range; Observational Study; Participant; Performance; Pharmaceutical Preparations; Physical Examination; Pilot Projects; Production; Property; Prospective Studies; Race; Risk; Sampling; Serum; Smoking; Testing; Uric Acid; Women' s Health; base; diabetes education; functional decline; interest; prevent; public health relevance; sex

DESCRIPTION (provided by applicant): Uric acid is rapidly gaining attention because of its seemingly contradictory properties in relation to brain function. In our prior cross-sectional, observational studies of community-dwelling adults, we have demonstrated that mildly elevated-- but still normal-- levels of serum uric acid are associated with significantly poorer cognitive performance and with greater cerebral ischemic burden, even after controlling for age, sex, race, education, diabetes, hypertension, smoking, and alcohol abuse. We have also demonstrated that individual differences in cerebral ischemia mediate the association between uric acid and mild cognitive dysfunction. Taken together, our results support the notion that even mild elevations of serum uric acid are associated with structural and functional brain changes, specifically involving the development of ischemic injury. These findings are interesting and suggest that a clinical trial may be warranted to determine whether uric acid lowering medications prevent or reverse mild cognitive dysfunction in elderly adults with high normal serum uric acid. However, the sample on which these findings were based was relatively small and the relationships were strictly cross-sectional. Therefore, the goal of this pilot project is to replicate these findings in a larger cross-sectional sample and extend our findings by determining whether high normal concentrations of serum uric acid are associated with mild cognitive dysfunction and adaptive functioning longitudinally. We are also seeking to determine whether any observed associations between uric and adaptive functioning are mediated by declines in cognition. To achieve these goals, we have applied for and been granted permission to analyze data from the Women's Health and Aging Study II (WHAS II), a prospective study of healthy elderly women. Participants of the WHAS II underwent serial physical examinations, blood draws (including serum uric acid), cognitive testing, and assessments of adaptive functioning. Should the findings from this investigation indicate that high normal serum uric acid increases the risk of mild cognitive dysfunction longitudinally, after controlling for other health, cardiovascular, and demographic variables it, this would provide powerful evidence further justifying the need for a clinical trial aimed at reducing serum uric acid production in elderly adults with mildly elevated uric acid. PUBLIC HEALTH RELEVANCE: The goal of this pilot project is to replicate and expand on our previous cross-sectional findings relating elevations in serum uric acid to mild cognitive dysfunction in elderly adults by examining both cross-sectional and longitudinal data from the Women's Health and Aging Study-II (WHAS-II). Should the findings from this investigation indicate that high normal serum uric acid increases the risk of mild cognitive dysfunction longitudinally, this would provide powerful evidence further justifying the need for a clinical trial aimed at reducing serum uric acid production in elderly adults with mildly elevated uric acid.

描述（由申请人提供）：尿酸因其与大脑功能看似矛盾的特性而迅速受到关注。在我们之前对社区居住的成年人进行的横断面观察性研究中，我们已经证明，血清尿酸水平轻度升高（但仍正常）与认知能力明显较差和脑缺血负担增加有关，即使在控制年龄、性别、种族、教育程度、糖尿​​病、高血压、吸烟和酗酒。我们还证明，脑缺血的个体差异介导尿酸与轻度认知功能障碍之间的关联。综上所述，我们的结果支持这样的观点：即使血清尿酸轻微升高也与大脑结构和功能的变化相关，特别是涉及缺血性损伤的发生。这些发现很有趣，表明可能需要进行临床试验来确定降尿酸药物是否可以预防或逆转血清尿酸正常高的老年人的轻度认知功能障碍。然而，这些发现所依据的样本相对较小，而且关系是严格的横截面关系。因此，该试点项目的目标是在更大的横截面样本中复制这些发现，并通过确定正常高浓度的血清尿酸是否与轻度认知功能障碍和纵向适应性功能相关来扩展我们的发现。我们还试图确定观察到的尿酸与适应性功能之间的关联是否是由认知能力下降介导的。为了实现这些目标，我们已申请并获得许可来分析女性健康与老龄化研究 II (WHAS II) 的数据，这是一项针对健康老年女性的前瞻性研究。 WHAS II 的参与者接受了一系列体检、抽血（包括血清尿酸）、认知测试和适应性功能评估。如果这项调查的结果表明，在控制其他健康、心血管和人口统计学变量后，正常高血清尿酸会纵向增加轻度认知功能障碍的风险，这将提供有力的证据，进一步证明有必要进行一项旨在减少尿酸轻度升高的老年人的血清尿酸产生。公共健康相关性：该试点项目的目标是通过检查来自妇女健康和老龄化的横断面和纵向数据，复制和扩展我们之前的横断面研究结果，即血清尿酸升高与老年人轻度认知功能障碍相关。研究-II (WHAS-II)。如果这项调查的结果表明，正常高血清尿酸会纵向增加轻度认知功能障碍的风险，这将提供有力的证据，进一步证明需要进行旨在减少尿酸轻度升高的老年人的血清尿酸产生的临床试验。 。