Cognition and Dialysis

描述（由申请人提供）：终末期肾病（ESRD）是美国的一个主要公共卫生问题，其发病率和流行率正在上升，主要是由于人口老龄化，糖尿病和高血压的发病率较高。老年人生活质量的一个主要决定因素是认知功能水平；然而，这在ESRD中尚未得到很好的研究。我们最近获得了一项R21拨款，以获得血液透析患者认知功能的初步数据。在目前的应用中，我们扩大了参与研究的参与者数量，并重点关注这些患者的纵向随访。目的是前瞻性地评估血液透析患者认知功能的范围和认知功能障碍发展的危险因素。我们的主要假设是，在血液透析患者中，认知功能障碍和脑结构异常的发生率很高，并且血浆总同型半胱氨酸（tHcy）、氧化应激、炎症和内皮功能障碍通过脑血管疾病途径与认知功能障碍相关。我们的主要目的是：1 .收集来自5个马萨诸塞州透析诊所（DCI）单位的312名血液透析患者的队列，评估认知功能的范围，并将结果与来自一般人群的年龄、性别和教育程度匹配的规范数据进行比较；2 .在1年、2年和3年的随访中，分别对240名、184名和115名患者的认知功能变化和这种变化的危险因素进行前瞻性评估。次要目的是对50名受试者进行脑MRI，评估萎缩、大血管和小血管疾病的患病率，以及弥散性贫血的减少，并将结果与几个对照组进行比较。R21阶段已经证实了成功完成该项目的可行性。首席研究员组建了一个由各自领域的专家组成的多学科研究小组。最新的生物分析将用于评估主要的危险因素。经过验证的神经认知评估工具将用于评估认知功能的主要结果。已经制定了评估普遍性的计划，统计分析表明有足够的能力来评估每一个主要目标。认知障碍严重影响老年人的生活质量。关于透析患者认知功能的数据不足，随着透析人群的老龄化，认知障碍将成为一个更大的问题。评估透析患者认知障碍发展或进展的患病率以及潜在危险因素对于提供可能减轻该患者群体认知障碍负担的潜在干预措施的线索至关重要。

DESCRIPTION (provided by applicant): End-stage renal disease (ESRD) is a major public health problem in the US and is increasing in incidence and prevalence, primarily due to an aging population with a higher incidence of diabetes and hypertension. A major determinant of the quality of life in the elderly is the level of cognitive function; however this has not been well studied in ESRD. We recently received an R21 grant to obtain preliminary data on cognitive function in hemodialysis patients. In the current application we extend the number of participants involved in the study and also focus on longitudinal follow-up of these patients. The goal is to prospectively evaluate the range of cognitive function and risk factors for development of cognitive impairment in hemodialysis patients. Our primary hypothesis is that there is a high prevalence of cognitive impairment as well as structural brain abnormalities in hemodialysis patients, and that total plasma homocysteine (tHcy), oxidative stress, inflammation and endothelial dysfunction are associated with cognitive impairment via a pathway of cerebrovascular disease. Our primary aims are 1: to assemble a cohort of 312 hemodialysis patients from 5 Massachusetts Dialysis Clinic Incorporated (DCI) units, assess the range of cognitive function, and compare the results with age-, gender- and education-matched normative data from the general population, and 2: to prospectively assess for change in cognitive function and risk factors for this change in 240, 184 and 115 patients in 1, 2 and 3 yrs of follow-up, respectively. The secondary aim is to perform brain MRI in 50 subjects, to evaluate the prevalence of atrophy, large and small vessel disease, and decreased diffusion anisitropy, and to compare the results with several control groups. The R21 phase has confirmed the feasibility of successfully completing this project. The principal investigator has assembled a multidisciplinary research team consisting of experts in each of their respective fields. The most up-to-date biological assays will be used to evaluate the primary risk factors of interest. Validated neurocognitive assessment instruments will be used to assess the primary outcome of cognitive function. Plans have been developed for evaluation of generalizability, and statistical analyses suggest adequate power to evaluate each of the primary aims. Cognitive impairment adversely affects the quality of life of the aging population. There are insufficient data on cognitive function in dialysis patients, and cognitive impairment will become more of a problem as the dialysis population ages. Evaluating the prevalence of as well as potential risk factors for development or progression of cognitive impairment in dialysis patients is essential to provide clues as to potential interventions that may reduce the burden of cognitive impairment in this patient population. NARRATIVE : Cognitive impairment adversely affects the quality of life of the aging population. There are insufficient data on cognitive function in dialysis patients, and cognitive impairment will become more of a problem as the dialysis population ages. Evaluating the prevalence of as well as potential risk factors for development or progression of cognitive impairment in dialysis patients is essential to provide clues as to potential interventions that may reduce the burden of cognitive impairment in this patient population.