Kidney function and cognitive and physical decline in older women

老年女性的肾功能以及认知和身体衰退

• 批准号: 7910495
• 负责人: JULIE LIN
• 金额: $ 34.91万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7910495
• 关键词: Aging; Albumins; Albuminuria; Biological Assay; Biological Markers; Blood; Blood Vessels; Bone Diseases; Brain; C-reactive protein; Chronic Kidney Failure; Cognitive; Communities; Creatinine; Data; Diabetic Angiopathies; Disease; Elderly; Epidemic; Etiology; Fibrinogen; Frequencies; Functional disorder; Glomerular Filtration Rate; Growth; Health; Healthcare; Impaired cognition; Individual; Inflammation; Inflammatory; Investigation; Kidney; Kidney Diseases; Kidney Failure; Life Style; Link; Longevity; Measurement; Measures; Mediating; Mediator of activation protein; Medical; Metabolism; Microalbuminuria; Minerals; Modeling; Morbidity - disease rate; Muscle; Nurses' Health Study; Outcome Measure; Participant; Physical Function; Plasma; Population; Prevalence; Prospective Studies; Public Health; Quality of life; Questionnaires; Receptors, Tumor Necrosis Factor, Type II; Renal function; Reporting; Research Infrastructure; Resources; Risk; Role; SF-36; Sampling; Spottings; TNFR-Fc fusion protein; Testing; Time; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; United States; Uremia; Urine; Vascular Diseases; Walking; Woman; Work; aged; aging population; clinical care; cognitive function; cohort; cost; falls; follow-up; functional decline; improved; inflammatory marker; innovation; mortality; neuromuscular; older women; population based; primary outcome; receptor; urinary; vascular inflammation

DESCRIPTION (provided by applicant): Progressive cognitive and physical function decline in the aging population in the United States requires a substantial allocation of healthcare resources. Aging is also associated with increased prevalence of chronic kidney disease. Advanced kidney failure is an important etiology of cognitive and physical dysfunction, likely mediated through vascular disease, abnormal mineral metabolism, and neuromuscular degeneration, but sparse data are available concerning the role of mild and moderate kidney failure. We hypothesize that mild and moderate chronic kidney disease will be independently associated with cognitive and physical decline in older adults. This prospective study will include 3700 community-dwelling women participating in the Nurses' Health Study who are aged 70 and older, have stored plasma from 1989 and 2000, stored urine from 2000, and who have undergone repeated cognitive function testing every two years. Physical function is assessed every four years by the physical component score of the Short Form-36, walking pace, and frequency of falls as reported on the questionnaires. Our measurements of cognitive and physical functioning have been validated as significant predictors of morbidity and mortality in population-based studies of older adults. We will assay plasma for creatinine, which will allow us to estimate GFR, and urine for microalbuminuria. A growth curve approach to multivariable modeling to test for associations between kidney dysfunction and subsequent 1) cognitive or 2) physical function decline will allow us to take advantage of multiple repeated measures of these outcomes obtained between 2000 and 2008. Specific aims of this proposal include evaluating how 1) baseline eGFR in 2000, 2) >25% eGFR decline between 1989 and 2000 (over 11 years), and 3) presence of microalbuminuria are related to cognitive and physical decline between 2000 and 2008 (over 8 years). We will also investigate whether inflammatory biomarkers, namely C- reactive protein, fibrinogen, and tumor necrosis factor a receptor-2, may potentially mediate associations between kidney dysfunction and functional decline. We will have >80% power for our aims. Completed and on-going work in this established cohort make this project extremely cost-effective. From a public health perspective, recognition of these associations may result in improving clinical care for the geriatric population through medical management strategies that slow progression of early and moderate kidney disease, cognitive impairment, and physical function decline. Thus, findings from this longitudinal, prospective study of a large cohort of older women will meaningfully improve the quality of life and longevity of community-dwelling older citizens.

描述（由申请人提供）：美国老龄化人口的渐进认知和身体机能下降需要大量的医疗资源分配。衰老也与慢性肾脏疾病的患病率增加有关。晚期肾衰竭是认知和物理功能障碍的重要病因，可能是通过血管疾病，异常矿物质代谢和神经肌肉变性介导的，但是关于轻度和中等肾脏衰竭的作用稀疏数据。我们假设轻度和中度的慢性肾脏疾病将与老年人的认知和身体下降独立相关。这项前瞻性研究将包括参加70岁及70岁以上护士健康研究的3700名社区居民妇女，从1989年和2000年开始存储血浆，从2000年储存了尿液，并且每两年进行一次重复的认知功能。每四年的身体成分得分每四年评估，如问卷所示，较短的表格-36，步行步伐和跌倒频率。我们对认知和身体功能的测量已被证实为对老年人的基于人群研究的发病率和死亡率的重要预测指标。我们将分析肌酐的等离子体，这将使我们能够估计GFR，并为微藻尿症尿液。 A growth curve approach to multivariable modeling to test for associations between kidney dysfunction and subsequent 1) cognitive or 2) physical function decline will allow us to take advantage of multiple repeated measures of these outcomes obtained between 2000 and 2008. Specific aims of this proposal include evaluating how 1) baseline eGFR in 2000, 2) >25% eGFR decline between 1989 and 2000 (over 11 years), and 3) presence of微量白蛋白尿与2000年至2008年（超过8年）之间的认知和身体下降有关。我们还将研究炎性生物标志物，即C-反应性蛋白，纤维蛋白原和肿瘤坏死因子A受体-2是否可能介导肾功能障碍与功能下降之间的关联。我们的目标将拥有> 80％的功率。在这个已建立的队列中完成和正在进行的工作使该项目变得极具成本效益。从公共卫生的角度来看，对这些关联的认识可能会通过医疗管理策略改善老年人群的临床护理，从而缓慢早期和中度肾脏疾病，认知障碍以及身体机能下降。因此，对大量老年妇女的纵向，前瞻性研究的结果将有意义地改善社区居住老年人的生活质量和寿命。