Neurocognition and Functional Performance in Older Veterans with CKD

描述(由申请人提供)： 项目摘要慢性肾脏疾病(CKD)在美国每5个老年人中就有1个受到影响，其中包括40多万名老年退伍军人，但受影响的个人甚至他们的医疗保健提供者往往没有意识到这一点。患有CKD的老年人患认知和身体功能障碍的风险明显更高，包括患痴呆症的风险增加40%，身体虚弱的风险增加75%。造成这一风险的因素尚不清楚；然而，最近的神经影像检查表明，与慢性肾脏病和肾功能减退相关的隐匿性脑病理负担大大增加。在CKD的背景之外，这些亚临床缺血性脑病的神经影像表现--静止性脑梗塞、白质高信号、萎缩和低灌流--与认知和身体功能下降有关。然而，还没有关于亚临床缺血性脑病作为CKD与身体和认知功能关系的中介的正式统计评估，也没有任何关于老年CKD患者认知和身体功能障碍模式的研究。我们假设患有CKD的老年退伍军人患有更大的亚临床脑缺血性疾病，这会导致神经认知和身体功能受损。在这项修订的提案中，我们将对社区无中风居住的老年退伍军人(年龄60-85岁)进行一项观察性队列研究，这些退伍军人患有不需要透析的CKD(N=150，平均分布在轻度、中度和重度CKD中)，以及一组没有CKD但在常见并存疾病糖尿病、高血压和心脏病方面频率匹配的对照组(N=50)。我们将获得1)肾脏疾病和功能(包括蛋白尿和肾脏生物标志物半胱氨酸氨基转移酶C)的定量测量，2)使用MRI的缺血性脑疾病，3)身体功能和表现，以及4)神经认知功能的多个领域。总体目标是评估慢性肾脏病和肾功能指标与MRI定义的亚临床缺血性脑病以及认知和身体功能的相关性。多变量分析将被用来确定CKD患者的功能缺陷和脑结构改变的模式。结构方程模型(SEM)将在考虑了高血压、糖尿病和心脏病等主要并存疾病后，研究亚临床缺血性脑病是否调节CKD和相关的肾功能指标与神经认知和身体功能的关系。这项研究的结果对于开发检测并最终预防老年CKD患者功能缺陷的方法至关重要，CKD是一个高度流行和快速增长的人群。 公共卫生相关性： 慢性肾脏病(CKD)影响着40多万名老年退伍军人，但往往未被认识到。老年CKD患者发生身体和认知缺陷的风险明显更高，但具体的缺陷模式和解释这些缺陷的机制尚不确定。然而，越来越多的证据表明，CKD患者患隐匿性脑血管疾病的风险增加，这可能会对大脑功能产生不利影响。这项拟议的研究将研究患有和不患有慢性肾脏疾病的老年退伍军人，以表征与肾脏疾病相关的身体功能和认知障碍的模式，并检查隐蔽血管疾病对大脑成像造成的负担增加是否导致这些与慢性肾脏病相关的缺陷。这些研究是努力保护患有CKD的老年退伍军人大脑功能的第一步，CKD是一个庞大且未得到充分认识的人群。

DESCRIPTION (provided by applicant): Project Summary Chronic Kidney Disease (CKD) affects 1 out of 5 older adults in the US including more than 400,000 older veterans yet is often unrecognized by affected individuals and even their healthcare providers. Older adults with CKD suffer from a markedly higher risk of cognitive and physical dysfunction, including a 40% greater risk of dementia and a 75% greater risk of physical frailty. The factors which account for this risk are unclear; however, recent neuroimaging investigations suggest a greatly increased burden of covert brain pathology in association with CKD and reduced kidney function. Outside the context of CKD, these neuroimaging findings of subclinical ischemic brain disease - silent brain infarcts, white matter hyperintensities, atrophy, and hypoperfusion - are associated with reduced cognitive and physical function. However, there has been no formal statistical evaluation of subclinical ischemic brain disease as a mediator of the relations of CKD to physical and cognitive function, nor any investigations of the patterns of cognitive and physical dysfunction in older adults with CKD. We hypothesize that older veterans with CKD suffer from a greater burden of subclinical ischemic disease of the brain, which results in impaired neurocognition and physical function. In this revised proposal, we will conduct an observational cohort study of stroke-free community-dwelling older veterans (ages 60-85) with CKD not requiring dialysis (N=150, evenly distributed among mild, moderate and severe CKD), and a control group without CKD but frequency-matched on the common co-morbid conditions diabetes, hypertension and cardiac disease (N=50). We will obtain quantitative measurements of 1) kidney disease and function (including albuminuria and the renal biomarker cystatin C), 2) ischemic brain disease using MRI, 3) physical function and performance, and 4) multiple domains of neurocognitive function. The overall aims are to estimate the association of CKD and renal function measures with MRI-defined subclinical ischemic brain disease and cognitive and physical function. Multivariate analyses will be employed to identify patterns of functional deficits and alterations of brain structure in CKD. Structural equations models (SEM) will examine whether subclinical ischemic brain disease mediates the relations of CKD and associated renal function measures to neurocognition and physical function after accounting for major co-morbid conditions including hypertension, diabetes, and cardiac disease. Results of this investigation will be of critical importance in the development of methods to detect and ultimately prevent functional deficits among older adults with CKD, a highly prevalent and rapidly growing population. PUBLIC HEALTH RELEVANCE: Chronic Kidney Disease (CKD) affects over 400,000 older veterans yet is frequently unrecognized. Older patients with CKD are at markedly higher risk for physical and cognitive deficit, but the specific patterns of deficits and the mechanisms which account for them are uncertain. However, there is increasing evidence that CKD patients have an increased risk of covert vascular disease of the brain, which could have adverse effects on brain function. The proposed research will study older veterans with and without chronic kidney disease to characterize the patterns of deficits in physical function and cognition associated with kidney disease, and examine whether an increased burden of covert vascular disease on brain imaging accounts for these deficits related to CKD. These investigations are the first steps in efforts to preserve brain function in older veterans with CKD, a large and under-recognized population.