Stroke and Cognitive Impairment in Aging Chronic Kidney Disease Patients

描述(申请人提供)：脑血管疾病在多大程度上导致老年慢性肾脏病(CKD)患者频繁的认知障碍尚未得到充分的测量。认知障碍和卒中导致服药不依从性加速，功能衰退，丧失独立性。这项纵向研究将使用脑磁共振成像(MRI)来检测症状性和静止性中风，使用结构化认知电池来检测损害，使用实验室数值来评估蛋白尿和炎症标记物，以衡量中风和白质疾病以及CKD特有因素在认知障碍中的作用。我们的长期目标是确定增加老年CKD和血液透析受试者认知损害、身体功能下降和丧失独立性的风险的因素。我们的中心假设是，中风和白质疾病在这些患者的认知功能障碍的发展中发挥了重要作用，但微血管内皮细胞损伤和炎症也是认知功能下降的重要因素。这项拟议研究的基本原理是，通过定义脑血管疾病和其他风险因素的作用，我们将能够在未来设计预防CKD患者认知障碍的措施。这项拟议的研究与美国国立卫生研究院的任务有关：开发知识，帮助减轻人类疾病和残疾的负担。在强大的初步数据的指导下，我们将通过我们的特定目标来检验我们的假设：1.(横断面)确定3b-5期CKD受试者(估计每1.73平方米肾小球滤过率[EGFR]d 45ml/min)和非CKD对照组受试者认知损害的基线患病率，并评估CKD受试者普遍存在的严重认知损害的危险因素。2.(主要目的，纵向)描述CKD受试者(A)基线和发病中风、白质疾病、EGFR、炎症、微量白蛋白尿、透析开始和(B)认知功能减退之间的关系。3.(纵向)比较CKD受试者和非CKD受试者3年间整体和特定领域认知功能减退的比率。我们将使用每年45分钟的认知电池测量450名CKD受试者(未进行基线透析)和150名年龄和种族匹配的非CKD对照组长达3年的认知功能，包括过渡到透析的CKD受试者在血液透析开始后的过渡区。事件中风将通过年度访谈、参与者电子医疗记录和大脑核磁共振检测来检测。这种方法是创新的，针对3b-5期CKD患者，那些最有可能经历认知能力下降的人，并使用脑磁共振来检测静止性中风和白质疾病。这项研究对于衡量临床和亚临床脑血管疾病和其他潜在的可改变的风险因素对认知能力下降的影响程度，克服设计积极和及时的干预措施以预防认知障碍的关键障碍具有重要意义。

DESCRIPTION (provided by applicant): The extent to which cerebrovascular disease contributes to the frequent cognitive impairment in aging chronic kidney disease (CKD) patients has not been adequately measured. Cognitive impairment and stroke result in medication noncompliance accelerated functional decline, and loss of independence. This longitudinal study will use brain magnetic resonance imaging (MRI) to detect symptomatic and silent incident stroke, a structured cognitive battery to detect impairment, and laboratory values to assess albuminuria and inflammatory markers, to measure the role of stroke and white matter disease and of factors specific to CKD in cognitive impairment. Our long-term goal is to identify factors that increase the risk of cognitive impairment, physical function decline, and loss of independence in aging CKD and hemodialysis subjects. Our central hypothesis is that stroke and white matter disease play large roles in the development of cognitive impairment in these patients, but that microvascular endothelial damage and inflammation are also important contributors to cognitive decline. The rationale for the proposed research is that by defining the role of cerebrovascular disease and other risk factors, we will enable future design of measures to prevent cognitive impairment in CKD patients. The proposed research is relevant to the NIH mission: to develop knowledge to help reduce the burden of disease and disability in humans. Guided by strong preliminary data, we will test our hypothesis through our Specific Aims: 1. (cross-sectional) Determine the baseline prevalence of cognitive impairment (both global and individual domains) in Stage 3b-5 CKD subjects (estimated glomerular filtration rate [eGFR] d 45 ml/min per 1.73 m2) and non-CKD control subjects, and assess risk factors for prevalent severe cognitive impairment in CKD subjects. 2. (Primary Aim, longitudinal) Characterize the association between (a) baseline and incident stroke, white matter disease, eGFR, inflammation, microalbuminuria, dialysis initiation and (b) cognitive decline over 3 years in CKD subjects. 3. (longitudinal) Compare rates of global and domain-specific cognitive decline over 3 years in CKD and non-CKD subjects. We will measure cognitive function using an annual 45-minute cognitive battery in 450 CKD subjects (not on dialysis at baseline) and 150 age- and race-matched non-CKD controls for up to 3 years of follow-up, including the transition zone after hemodialysis initiation for CKD subjects who transition to dialysis. Incident strokes will be detected via annual interviews, participant electronic medical records, and brain MRIs. The approach is innovative by targeting Stage 3b-5 CKD subjects, those most likely to experience cognitive decline, and using brain MRI to detect silent strokes and white matter disease. The research is significant in measuring the extent to which clinical and subclinical cerebrovascular disease and other potentially modifiable risk factors contribute to cognitive decline, to overcome the critical barrier to designing aggressive and timely interventions to prevent cognitive impairment.