Stroke and Cognitive Impairment in Aging Chronic Kidney Disease Patients

描述（由申请方提供）：尚未充分测量脑血管疾病导致老年慢性肾脏病（CKD）患者频繁认知障碍的程度。认知功能障碍和脑卒中导致服药不依从性加速功能下降，丧失独立性。这项纵向研究将使用脑磁共振成像（MRI）检测有症状和无症状的卒中事件，使用结构化认知成套测试检测功能障碍，使用实验室检查值评估蛋白尿和炎症标志物，测量卒中和白色疾病以及CKD特异性因素在认知功能障碍中的作用。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障碍、身体功能下降和独立性丧失风险的因素。我们的中心假设是，中风和白色疾病在这些患者的认知功能障碍的发展中起着重要作用，但微血管内皮损伤和炎症也是认知功能下降的重要因素。拟议研究的基本原理是，通过定义脑血管疾病和其他危险因素的作用，我们将能够在未来设计预防CKD患者认知障碍的措施。拟议的研究与NIH的使命有关：开发知识以帮助减轻人类疾病和残疾的负担。在强有力的初步数据的指导下，我们将通过我们的具体目标来检验我们的假设：1。（横断面）确定3b-5期CKD受试者（估计肾小球滤过率[eGFR] d <45 ml/min/1.73 m2）和非CKD对照受试者中认知功能障碍（总体和个体领域）的基线患病率，并评估CKD受试者中普遍存在的重度认知功能障碍的风险因素。2.（主要目的，纵向）表征CKD受试者3年内（a）基线和卒中事件、白色疾病、eGFR、炎症、微量白蛋白尿、透析开始和（B）认知下降之间的相关性。3.（纵向）比较CKD和非CKD受试者3年内的整体和领域特异性认知下降率。我们将在450例CKD受试者（基线时未接受透析）和150例年龄和种族匹配的非CKD对照中使用每年45分钟认知组合测量认知功能，随访时间长达3年，包括开始血液透析后转为透析的CKD受试者的过渡区。将通过年度访谈、参与者电子病历和脑部MRI检测卒中事件。该方法是创新的，目标是3b-5期CKD受试者，那些最有可能经历认知能力下降，并使用脑MRI检测无症状中风和白色疾病。该研究在测量临床和亚临床脑血管疾病以及其他潜在可改变的风险因素对认知能力下降的影响程度方面具有重要意义，可以克服设计积极和及时干预措施以预防认知障碍的关键障碍。

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.