PROJECT SUMMARY/ABSTRACT Chronic kidney disease and cognitive impairment are highly prevalent diseases in older adults and may share a common pathophysiology. Evaluations of the association between kidney disease and cognitive function have focused almost exclusively on glomerular function as the measure of kidney health. Kidney function is not limited to the glomerulus, and measures such as estimated glomerular filtration rate and albuminuria do not necessarily capture the health of the kidney tubules. Kidney tubules are important for acid/base homeostasis, nutrient reabsorption, toxin secretion, and hormone production, and are highly prognostic for kidney failure even in the presence of normal estimated glomerular filtration rate and albuminuria levels. In this proposal, I aim to characterize the relationship of kidney tubule dysfunction with cognitive decline, incident dementia and functional MRI measures of cerebrovascular disease, and evaluate whether these kidney tubule markers provide information independent of estimated glomerular filtration rate and albuminuria levels. Using the Systolic Blood Pressure Intervention Trial (SPRINT) data, I will evaluate the relationships between urinary markers of kidney tubule dysfunction with MRI measures of brain health, including white matter grade, cerebral blood flow, and total brain volume. Furthermore, I will provide novel data on the relationship of kidney tubule dysfunction with longitudinal changes in cognitive function and incident dementia among community-living older adults in the Healthy Aging and Body Composition Study. Through this proposal, I will determine the global relationship of kidney health (both glomerular and tubular) with cognitive health, including functional measures of cerebral vascular disease, cognitive decline and incident dementia. This research will also catalyze my career development as an emerging kidney and cognition scientist.

PROJECT NARRATIVE Studies evaluating kidney disease and cognitive impairments have focused on markers of glomerular health (eGFR and ACR), which do not capture the health or function of kidney tubules. In this project, we will determine the relationships of kidney tubule health with functional measures of cerebrovascular disease, cognitive decline and incident dementia. Doing so will provide additional insight into the mechanisms that underlie the kidney-brain axis which may ultimately provide preventive or therapeutic targets.