Relationship between kidney function and cognitive decline and moderating effects of race and SES

Abstract

There is limited research as to whether pre-clinical chronic kidney disease (CKD) measured by a combination of kidney function markers such as the estimated glomerular filtration rate (eGFR), albuminuria, and Cystatin-C have an impact on cognition. Understanding kidney function decline as a potential early marker for cognitive decline has important public health implications given the high societal burden of clinically diagnosed kidney disease and cognitive disorders. The Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study wave 1 and 3 datasets were used for this analysis. HANDLS Wave 1 data were collected from year 2004 to 2009, and wave 3 from year 2009 to 2013. In Aim 1, mixed effects models with interaction terms were constructed to examine the effects of time-varying eGFR on several cognitive outcomes. A backward elimination method was used to trim the models of non-significant four-way interactions of eGFR*Age*Race*Poverty and all lower-order interactions. In Aim 2, mixed effects models with interaction terms similar to those used in Aim 1 were constructed to examine the effects of baseline eGFR, urine albumin and Cystatin-C on the same set of cognitive outcomes. All significant interactions were examined by interaction plots for racial and SES subgroups. The analytical cohorts included 1,206 participants for aim 1 and 638 participants for aim 2 at baseline. The main hypothesis that African Americans living below poverty would have the worst impact of lower kidney function on cognition was not supported. Over about 5 years, eGFR over time was associated with decline in verbal learning and memory among Whites below poverty. In addition, the associations between baseline kidney function markers and cognitive decline were highly equivocal. Higher baseline Cystatin-C were found to be associated with cognitive decline in attention, and this association was no longer significant after adjusting for cardiovascular factors and inflammation. It is possible that kidney function is broadly related to performance in the domains of attention, working memory and executive function. These findings suggest that functional changes in the kidney precedes cognitive decline among Whites, especially those living below poverty.