Stroke and Cognitive Impairment in Aging Chronic Kidney Disease Patients

描述（由申请人提供）：脑血管疾病在多大程度上导致老年慢性肾脏疾病（CKD）患者频繁的认知障碍尚未得到充分的测量。认知障碍和中风导致服药不遵医嘱加速功能下降和丧失独立性。这项纵向研究将使用脑磁共振成像（MRI）来检测症状性和无症状性卒中，使用结构化认知电池来检测损伤，使用实验室值来评估蛋白尿和炎症标志物，以测量卒中和白质疾病以及CKD特异性因素在认知损伤中的作用。我们的长期目标是确定在老年CKD和血液透析患者中增加认知障碍、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，中风和白质疾病在这些患者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能力下降的重要因素。提出这项研究的基本原理是，通过确定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患者认知功能障碍的措施。拟议的研究与NIH的使命相关：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：（横截面）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对照受试者中认知障碍的基线患病率（包括全球和个体），并评估CKD受试者中普遍存在的严重认知障碍的危险因素。2. （主要目的，纵向）描述CKD受试者3年以上基线与卒中、白质疾病、eGFR、炎症、微量白蛋白尿、透析起始和(b)认知能力下降之间的关系。3. （纵向）比较慢性肾病和非慢性肾病受试者3年内整体和特定领域认知能力下降的比率。我们将对450名CKD受试者（基线时未进行透析）和150名年龄和种族匹配的非CKD对照组进行长达3年的随访，包括血液透析开始后过渡到透析的CKD受试者的过渡区，使用每年45分钟的认知电池来测量认知功能。突发中风将通过年度访谈、参与者电子医疗记录和脑部核磁共振检查来检测。该方法的创新之处在于针对3b-5期CKD患者，这些患者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质疾病。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危险因素对认知能力下降的影响程度方面具有重要意义，有助于克服设计积极及时的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.