LAS VEGAS – Patients on dialysis for end-stage renal disease have a high burden of impaired executive function that’s typically missed by clinicians, Dr. Daniel E. Weiner said at a meeting sponsored by the National Kidney Foundation.
Vascular dementia, which is much more common than Alzheimer’s disease in patients with chronic kidney disease (CKD), impairs executive function and is associated with anatomic white matter brain disease. Executive function is the cognitive domain concerned with attention, processing speed, reasoning, planning, and problem solving. Clinicians tend to miss the presence of cognitive impairment in patients with CKD because they typically rely upon the Mini-Mental State Examination (MMSE) to screen for impaired cognition. And the MMSE focuses on memory difficulties, which are more common in Alzheimer’s disease, rather than the more subtle domain of executive function, he explained.
Dr. Daniel E. Weiner
"We’re trying to teach (CKD patients) about complex topics such as fluid restriction, medication management, and salt intake, and you wonder if it just goes in one ear and out the other because they’re not able to process these complicated issues," observed Dr. Weiner, a nephrologist at Tufts University, Boston.
Dr. Weiner was coauthor of a recent cross-sectional cohort study in which 314 hemodialysis patients at six Boston-area hemodialysis units completed a comprehensive battery of neuropsychological tests assessing memory and executive function. The patients scored markedly worse than general population norms on executive function, but not on memory performance. Moreover, impaired executive function was highly prevalent even in patients with a normal MMSE of 24 or more. The take-home message: be cautious in using an MMSE score of less than 24 to screen for cognitive impairment in dialysis patients (Neurology 2013;80:471-80).
Moderate to severe cognitive impairment is also prevalent in patients on peritoneal dialysis, as shown by investigators at the University of Minnesota. They gave a battery of nine validated neuropsychological tests to 51 peritoneal dialysis patients, 338 hemodialysis patients, and 101 controls without CKD who were matched for age and comorbid conditions. Of the peritoneal dialysis cohort, 31% had severe cognitive impairment, as did 37% of the hemodialysis group and 13% of controls. In an adjusted logistic regression model, peritoneal dialysis was associated with a 2.5-fold increased risk of moderate to severe global cognitive impairment, compared with the no-CKD controls, while hemodialysis patients had a similar 3.16-fold increased risk (Am. J. Kidney Dis. 2011;57:612-20).
"That’s a remarkably high prevalence: one-third of dialysis patients in a moderately well educated Minnesota population with access to medical care performed poorly enough on a neurocognitive battery to be classified as severely cognitively impaired, meaning they flubbed on two different domains of cognitive function," Dr. Weiner commented.
The effect of dialysis itself upon cognition is a matter of continuing controversy. Although some nephrologists posit that a more intensive dialysis regimen would result in improved cognitive performance, that hasn’t been borne out in analyses to date (Kidney International 2011;79:14-22).
"This suggests that the cognitive impairment we see in dialysis patients isn’t related to the dialysis dose. It’s not related to retained solutes, but is more related to the – for lack of a better word – bad humors patients have been exposed to for many years and which have put them into a situation where they require dialysis," according to Dr. Weiner.
"We have patients that drop their systolic blood pressure by 20, 30, 40, even unfortunately 80 mm Hg during dialysis. You can’t imagine that this is good for you. We’re inducing transient microvascular ischemia, which is ultimately manifest structurally: in the kidney we get fibrosis, in the brain we get white matter disease," he continued.
Cognitive dysfunction is associated with increased mortality risk even in CKD patients who are not dialysis dependent. In an analysis of National Health and Nutrition Examination Survey III data, non–dialysis dependent CKD patients in the lowest quartile in terms of cognitive score had a twofold increased risk of mortality, compared with those in the highest quartile (Am. J. Nephrol. 2012;35:49-57).
Chronic kidney disease as defined by an estimated glomerular filtration rate below 60 mL/min/1.73 m2 is also a cardiovascular disease risk equivalent for stroke. Dr. Weiner and coworkers showed that the stroke rate in patients with CKD but no known cardiovascular disease is elevated to roughly the same extent as in patients with known cardiovascular disease but no CKD (Am. J. Kidney Dis. 2006;48:392-401).
More recently, Dr. Weiner and his colleagues showed in a brain MRI study that hemodialysis patients not only have far more white matter disease and cerebral atrophy than controls without kidney disease, they also have a high prevalence of previously unrecognized strokes. The cross-sectional study involved 45 hemodialysis patients and 67 controls, all without a history of stroke. Impressively, 18% of the hemodialysis patients had evidence of a small-vessel infarct on MRI and another 8% had a large-vessel infarct (Am. J. Kidney Dis. 2013;61:271-8).