Low 25-Hydroxyvitamin D Levels and Cognitive Impairment in Hemodialysis Patients

Abstract

SummaryBackground and objectives 25-hydroxyvitamin D (25[OH]D) deficiency and cognitive impairment are both prevalent in hemodialysis patients in the United States. This study tested the hypothesis that 25(OH)D deficiency may be associated with cognitive impairment because of its vasculoprotective, neuroprotective, and immunemodulatory properties.Design, setting, participants, & measurements This cross-sectional analysis involved 255 patients enrolled in the Dialysis and Cognition Study between 2004 and 2012. In linear regression models, 25(OH)D was the exposure variable; it was used first as a continuous variable and then stratified as deficient (,12 ng/ml), insufficient (12 to ,20 ng/ml), and sufficient ($20 ng/ml). Principal component analysis was used to obtain the memory and the executive function domains from the individual neurocognitive tests. Scores on individual tests as well as on the memory and executive function domains were the outcome variables. Multivariable models were adjusted for age, sex, race, education, and other potential confounding variables.Results Mean serum 25(OH)D 6 SD was 17.267.4 ng/ml, with 14%, 55%, and 31% of patients in the deficient, insufficient, and sufficient groups, respectively. Patients in the deficient group were more likely to be women, African American, and diabetic and to have longer dialysis vintage. Conclusions 25(OH)D deficiency in hemodialysis patients is associated with worse cognitive function, particularly in domains that assess executive function.

Kidney–brain crosstalk in the acute and chronic setting

“…89 Vitamin D deficiency in patients undergoing haemodialysis is associated with reduced cognitive function compared to cognitive function in vitamin D sufficient patients undergoing haemodialysis, particularly in domains assessing executive function; an associ ation of vitamin D with memory has not been shown. 84 FGF-23 is a phosphaturic hormone that is primarily expressed in bone, but is also found in high concentrations within the brain. 90 In a cohort of patients undergoing maintenance haemodialysis, high FGF-23 levels were associated with cognitive impairment, particularly in relation to composite memory score.…”

Cognitive Impairment in Chronic Kidney Disease-Prevalence, Mechanisms and Consequences

“…While vitamin D deficiency is a well-known risk factor for cognitive impairment in the general population and it has been hypothesized that this association is even stronger in CKD patients, studies in CKD patients are sparse [50]. So far, two studies reported an association of low vitamin D levels with cognitive impairment, one study recruiting hemodialysis patients [51] and the other peritoneal dialysis patients [52]. The only study which included patients with and without dialysis observed no significant association between vitamin D levels and cognitive function in multivariable models [53].…”

Vitamin D

“…Relative to most studies of cognitive impairment in the general non-CKD population, this cohort is relatively young; mean age was 63615 years, and some participants were as young as 18 years old (6). From a dialysis population perspective, as noted by Shaffi et al (5), this young group was compared with the US Renal Data System age distribution, and dialysis vintage was short; over 40% of the cohort were incident dialysis patients (,12 months), and mean vintage was 14 months. Thus, the duration of the cognitive impairment process that could be attributed to dialysis treatment was also relatively short.…”

“…In an important report in this issue, Shaffi et al (5) found that lower 25-hydroxyvitamin D [25(OH)D] levels were associated with an increased likelihood of impairment in the cognitive domain of executive function but not memory in a cross-sectional analysis of 255 hemodialysis patients in the Dialysis and Cognition Study. Shaffi et al (5) used a well designed detailed battery of cognitive tests that measured global function, immediate and delayed memory, and several aspects of executive function, including processing speed, attention, and abstract reasoning.…”

“…Vitamin D is believed to exert its neuroprotective effects through multiple pathways well described by Shaffi et al (5); it can modulate neuronal calcium homeostasis and vascular calcification, hypertension, inflammation, and immune function among other roles. An association between the vitamin D receptor gene and Alzheimer's disease has also been described, with the implication that the receptor genotype may be related to neurodegenerative disease and neuronal damage by altering vitamin D-mediated pathways (8).…”