Cognitive Impairment in CKD: Pathophysiology, Management, and Prevention

Abstract

Patients with chronic kidney disease (CKD) are at substantially higher risk for developing cognitive impairment compared with the general population, and both lower glomerular filtration rate and the presence of albuminuria are associated with the development of cognitive impairment and poorer cognitive function. Given the excess of vascular disease seen in individuals with CKD, cerebrovascular disease is likely the predominant pathology underlying these associations, though impaired clearance of uremic metabolites, depression, sleep disturbance, anemia, and polypharmacy may also contribute. Modification of vascular disease risk factors may be helpful in limiting decline, though definite data are lacking. Specific to CKD, targeting a low blood pressure and reduction in albuminuria with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may slow cognitive decline, albeit modestly. Initiation of dialysis can improve severe impairment associated with uremia but does not appear to affect more subtle chronic cognitive impairment. In contrast, kidney transplantation appears to lead to improved cognitive function in many transplant recipients, suggesting that dialysis methods do not provide the same cognitive benefits as having a functioning kidney. Management of patients with both CKD and cognitive impairment should include a comprehensive plan including more frequent follow-up visits; involvement of family in shared decision making; measures to improve compliance, such as written instruction and pill counts; and a focus on advance directives in conjunction with an emphasis on understanding an individual patient's life goals. Further research is needed on novel therapies, including innovative dialysis methods, that aim to limit the development of cognitive impairment, slow decline in those with prevalent impairment, and improve cognitive function.

Keywords: Chronic kidney disease (CKD); cerebrovascular disease; cognitive impairment; dementia; dialysis; end-stage renal disease (ESRD); review; uremic metabolites; vascular disease.

Figure 1.

Cognitive impairment in dialysis patients. A comprehensive battery of neurocognitive tests was administered in the first hour of hemodialysis to 314 patients and cognitive impairment was defined using methodology based on that described by Murray et al. Only 30% of hemodialysis patients had intact cognitive performance, while more than half had moderate or severe cognitive impairment. Extracted from data reported in Sarnak et al.

Figure 2.

Proposed pathophysiology of chronic kidney disease-related cognitive impairment. Abbreviations: CVD, cardiovascular disease; GFR, glomerular filtration rate.

Figure 3.

Distribution of brain magnetic resonance imaging (MRI) white matter disease and cerebral atrophy grades for individuals receiving maintenance hemodialysis versus individuals without known chronic kidney disease. Hemodialysis patients consistently displayed more severe white matter damage and more cerebral atrophy than controls. Black = hemodialysis group, white = control group without reported kidney disease. Higher grades correspond to more white matter disease or greater atrophy. Reproduced from Drew et al, with permission of the National Kidney Foundation.

Figure 4.

Hemodialysis (HD) consistently induced a decrease in cerebral blood flow (CBF) in elderly patients during the course of an HD treatment. The decrease in blood flow was observed across multiple different brain regions, as measured using positon emission tomography–commputed tomography. Image ©2018 American Society of Nephrology; reproduced from Polinder-Bos et al with permission of the copyright holder.