Chronic Kidney Disease Associated with Worsening White Matter Disease and Ventricular Enlargement

Prashanthi Vemuri, Cynthia Davey, Kirsten L. Johansen, Samantha M. Zuk, Robert I. Reid, Kaely B. Thostenson, Ashritha L. Reddy, Clifford R. Jack, David S. Knopman, Anne M. Murray

Research output: Contribution to journalArticlepeer-review


Background: Chronic kidney disease (CKD), a growing public health issue in the elderly, is associated with increased risk of cognitive impairment. Objective: To investigate the mechanisms through which CKD impacts brain health using longitudinal imaging. Methods: We identified 97 participants (74 CKD and 23 non-CKD) from the BRINK (BRain IN Kidney Disease), a longitudinal study of CKD with two MRI scans (baseline and 3-year follow-up). We measured the associations between baseline and change in kidney disease biomarkers of estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR), considered a measure of microvascular inflammation, and imaging outcomes of cortical thickness and ventricular volume from structural MRI, white matter hyperintensities (WMH) volume from FLAIR images, and fractional anisotropy of the corpus callosum (FACC). Results: There were white matter-specific changes as observed by increased WMH volume and decreased FACC in CKD participants, as well as ventricular volume increase in both CKD and non-CKD groups reflective of aging-related changes. Decline in eGFR was associated with decrease in the FACC, suggesting that subtle early white matter changes due to kidney disease can be captured using DTI. An increase in UACR was associated with increase in ventricular volume. Conclusion: Our results support the role of eGFR as a measure of kidney microvascular disease which is associated with concurrent white matter damage in CKD. Future work is needed to investigate the possible link between endothelial microvascular inflammation (as measured by an increased UACR) and ventricular volume increase.

Original languageEnglish (US)
Pages (from-to)1729-1740
Number of pages12
JournalJournal of Alzheimer's Disease
Issue number4
StatePublished - 2021


  • Brain health
  • chronic kidney disease
  • diffusion tensor imaging
  • white matter damage
  • white matter hyperintensities

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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