Chronic Renal Dysfunction and Ischemic Brain Disease

描述（由申请人提供）：与一般人群相比，肾功能不全患者的死亡率非常高，功能和认知障碍明显，部分原因是血管疾病加速。尽管大多数报告都集中在与心脏病相关的风险因素和结局上，但加速性血管疾病对这些患者脑血管结局的影响尚未明确，可能会显著导致其明显的认知障碍。尽管一些研究报告肾功能不全患者卒中风险增加，但尚未确定与临床和亚临床卒中相关的风险因素和结局。我们假设，肾功能不全患者，通过促进血管疾病加速的因素，临床和亚临床卒中的风险较高，这有助于肾脏疾病患者认知功能障碍和痴呆的高患病率。本研究的总体目的是确定肾功能不全与临床和亚临床卒中风险之间的相关性，确定特定的卒中风险因素，并量化慢性肾功能不全（CRI）和终末期肾病（ESRD）患者的相关认知功能障碍。拟议的研究将涉及一系列观察性研究。首先，将使用多中心前瞻性队列研究的数据，估计肾功能不全与临床卒中之间的关联，并确定CRI和ESRD患者的卒中风险因素。接下来，使用作为这些研究的一部分收集的MRI和神经精神病学数据，我们将确定CRI患者是否有更高的亚临床脑梗死风险，以及这是否会导致痴呆的风险更高。最后，将对血液透析患者进行认知功能的MRI成像和纵向测量，以确定亚临床脑梗死的风险因素，并确定这些梗死与认知能力下降之间的关系。这些研究通过阐明卒中的相关风险因素和不良结局，可能会导致开发新的策略来诊断和预防肾病患者的缺血性脑疾病，最终改善这些患者的预后。

DESCRIPTION (provided by applicant): Patients with renal dysfunction suffer from extraordinarily high rates of mortality and marked functional and cognitive impairment compared to the general population, in part due to accelerated vascular disease. Although the majority of reports have focused on risk factors and outcomes associated with cardiac disease, the impact of accelerated vascular disease on cerebrovascular outcomes among these patients are not well defined and may contribute significantly to their marked cognitive impairment. Although a few studies have reported an increased risk of stroke among patients with renal dysfunction, risk factors and outcomes associated with clinical and subclinical stroke have not been identified. We hypothesize that patients with renal dysfunction, through factors which promote accelerated vascular disease, are at a higher risk of clinical and subclinical stroke, which contributes to a high prevalence of cognitive dysfunction and dementia in patients with renal disease. The overall objectives of this study are to determine the association between renal dysfunction and risk of clinical and subclinical stroke, identify specific stroke risk factors, and quantify the associated cognitive dysfunction among patients with chronic renal insufficiency (CRI) and end-stage renal disease (ESRD). The proposed research will involve a series of observational studies. First, the association between renal dysfunction and clinical stroke will be estimated and stroke risk factors among CRI and ESRD pts will be identified, using data from multicenter prospective cohort studies. Next, using MRI and neuropsychiatric data collected as part of one these studies, we will determine whether patients with CRI are at higher risk for subclinical brain infarcts, and whether this contributes to a higher risk of dementia. Finally, MRI imaging and longitudinal measurements of cognitive function will be performed on hemodialysis patients, to determine risk factors for subclinical brain infarcts and define the relationship between these infarcts and cognitive decline. These studies, by clarifying associated risk factors and adverse outcomes of stroke, could result in the development of new strategies to diagnose and prevent ischemic brain disease in patients with renal disease, ultimately leading to an improved prognosis for these patients.