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.
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