Cognition and Vascular Disease in Dialysis Patients

描述(由申请人提供)： 终末期肾病(ESRD)在美国是一个主要的公共卫生问题，其发病率和患病率正在增加，这主要是由于人口老龄化，糖尿病和高血压的发病率更高，他们正在达到ESRD。老年人生活质量的一个主要决定因素是认知功能水平。在目前的提案中，我们计划评估透析患者的认知功能，并评估认知障碍的危险因素。我们的基本假设是，透析患者存在较高的认知障碍发生率，血浆总同型半胱氨酸(THcy)、氧化应激和炎症通过大小血管脑血管疾病与认知障碍相关。 在赠款的R21阶段，我们计划评估从波士顿透析诊所(DCI)部门招募40名患者并进行详细的认知测试和神经检查，以及分析tHcy、氧化应激和炎症标志物的可行性。如果达到R21阶段的里程碑，我们计划进入R33阶段，并从另外4个DCI门诊病房集合250名透析患者。R33的主要目的将是评估认知功能的范围，并将其与普通人群中年龄、性别和教育匹配的正常值进行比较；评估tHcy、氧化应激和炎症标志物是否与认知功能有关；以及评估认知功能在两年内发生变化的风险因素。 首席调查员组建了一个多学科研究小组，由各自领域的世界知名专家组成。将使用最新的生物测定来评估感兴趣的主要风险因素。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。已经制定了评估概括性的计划，统计分析表明有足够的能力评估每个主要目标。 认知障碍会对老龄人口的生活质量产生不利影响。有关透析患者认知功能的数据有限，随着透析人群的老龄化，认知障碍可能会成为一个更严重的问题。评估认知障碍的患病率和潜在的危险因素可能会导致在这一患者群体中进行干预试验，以减轻认知障碍的负担。

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 who are reaching ESRD. A major determinant of the quality of life in the elderly is the level of cognitive function. In the current proposal we plan to assess cognitive function in dialysis patients and to evaluate risk factors for cognitive impairment. Our primary hypothesis is that there is a high prevalence of cognitive impairment in dialysis patients, and that total plasma homocysteine (tHcy), oxidative stress and inflammation are associated with cognitive impairment via large and small vessel cerebrovascular disease. In the R21 phase of the grant we plan to assess the feasibility of recruiting 40 patients from the Boston Dialysis Clinic Inc. (DCI) unit and performing detailed cognitive testing and neurological exams, and assaying for tHcy, measures of oxidative stress and inflammatory markers. If the milestones are met for the R21 phase, we plan to proceed to the R33 phase and assemble a cohort of 250 dialysis patients from an additional 4 outpatient DCI units. The primary aims of the R33 will be to assess the range of cognitive function, and compare it with age, gender and education matched norms in the general population; to evaluate whether there is an association between tHcy, oxidant stress and inflammatory markers with cognitive function; and to evaluate risk factors for change in cognitive function over a two year follow-up. The principal investigator has assembled a multidisciplinary research team consisting of world-renowned 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 limited data on cognitive function in dialysis patients, and cognitive impairment is likely to become more of a problem as the dialysis population ages. Evaluating the prevalence of, as well as potential risk factors for, cognitive impairment may lead to intervention trials to reduce the burden of cognitive impairment in this patient population.