Does Hemodialysis Cause Dementia?
Abstract & Commentary
By Joseph E. Safdieh, MD, Assistant Professor of Neurology, Weill Medical College, Cornell University. Dr. Safdieh reports no financial relationship relevant to this field of study.
Synopsis: Moderate-to-severe cognitive impairment is common and under diagnosed in hemodialysis patients.
Source: Murray AM, et al.Cognitive Impairment in Hemodialysis Patients is Common. Neurology. 2006;67:216-223.
Hemodialysis patients are at increased risk of cognitive dysfunction due to metabolic disturbances, older age, and a high prevalence for cerebrovascular disease, diabetes, and hypertension. In this study, Murray and colleagues utilized neuropsychological testing to systematically measure function across multiple cognitive domains in 374 older hemodialysis patients (mean age = 71.2 years) and 101 age- and sex-matched controls. The controls were free of any chronic renal disease. The prevalence of cognitive impairment in the hemodialysis patients was high, with 73.4% of patients demonstrating moderate to severe cognitive impairment. Of the 13.9% that demonstrated mild impairment, only 12.7% were cognitively normal. Only 2.9% of these patients had any documented history of cognitive impairment. Factors associated with higher frequency of severe cognitive impairment in the hemodialysis cohort included history of stroke, < 8 years of education, and large dialysis volume. When compared to the control group, the hemodialysis group had a significantly higher risk of severe cognitive impairment (odds ratio, 3.54) after adjusting for age, sex, race, education, depression, diabetes, hypertension, and stroke. Murray et al suggest that this degree of cognitive impairment in dialysis patients may impede their ability to comply with dialysis schedules and manage increasingly complex medication regimens for their comorbid illnesses. Murray et al propose that a potential pathophysiological mechanism of cognitive impairment caused by hemodialysis is cerebral ischemia due to hypoperfusion induced by rapid fluid shifts. Two of the features associated with higher risk of cognitive impairment are modifiable—stroke and higher dialysis volume. Murray et al suggest that stroke prevention in dialysis patients should be aggressive.
In the 1970s and 1980s there was widespread recognition of a dementing illness occurring in dialysis patients, so-called dialysis dementia or dialysis encephalopathy. Aluminum, the culprit in this condition, was subsequently removed from dialysate, causing the frequency of dialysis dementia to decrease significantly. The general consensus among physicians was that cognitive impairment was no longer a significant problem caused by dialysis. The study by Murray et al calls that notion into serious question. The results suggest that the process of hemodialysis itself may be detrimental to cognitive function, especially in patients with cerebrovascular disease. The main weakness of the study is that it is not clear how much of the cognitive impairment is due to the underlying renal disease, since the control group excluded patients with renal disease. However, the fact that higher dialysis volume was an independent risk factor for severe cognitive dysfunction does, at least, partly implicate the actual process of hemodialysis. Whether the cause of cognitive impairment is intermittent cerebral hypoperfusion due to fluid shifts, as suggested by Murray et al, is yet to be determined. Future studies prospectively following cognitive function in end-stage renal disease patients who are randomized to start or delay dialysis, would certainly be helpful in further elucidating this matter. Neurologists should be vigilant about screening for cognitive impairment in patients on hemodialysis, and should aggressively treat modifiable cerebrovascular risk factors, as this may protect against severe cognitive impairment.