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Kidney Week

Abstract: TH-PO654

Association of CKD Markers with Dementia Markers on Brain MRI: The ARIC Study

Session Information

  • Geriatric Nephrology
    November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Geriatric Nephrology

  • 1100 Geriatric Nephrology

Authors

  • Scheppach, Johannes B., Johns Hopkins University, Baltimore, Maryland, United States
  • Wu, Aozhou, The Johns Hopkins University, Baltimore, Maryland, United States
  • Gottesman, Rebecca F., Johns Hopkins University, Baltimore, Maryland, United States
  • Mosley, Tom, Univ. of Miss. Med Center, Jackson, Mississippi, United States
  • Grams, Morgan, Johns Hopkins University, Baltimore, Maryland, United States
  • Sharrett, Richey, Johns Hopkins, Baltimore, Maryland, United States
  • Coresh, Josef, Welch Center for Prevention, Epidemiology & Clinical Research, Baltimore, Maryland, United States
  • Koton, Silvia, Tel Aviv University and Johns Hopkins University, Tel Aviv, Israel
Background

Urine albumin-creatinine-ratio (UACR) and estimated glomerular filtration rate (eGFR) define chronic kidney disease (CKD) and are associated with an increased risk of dementia and cognitive impairment. Such pathologies are accompanied with damage to the structural integrity of the brain, which can be seen using magnetic resonance imaging (MRI). We therefore examined the association of ACR and eGFR with MRI structural brain abnormalities in participants in the Atherosclerosis Risk in Communities (ARIC) study.

Methods

We studied 1,525 ARIC participants aged 67-90 years who attended visit 5 (2011-2013), and had a brain MRI scan performed, and eGFR based on cystatin C and UACR measured. We analyzed the association of UACR and eGFR with reduced brain volume, increased white matter hyperintensity (WMH) volume, micro-hemorrhages and brain infarcts using linear and logistic regression models, adjusted for age, sex, race, education, Apolipoprotein E4 level, smoking, body mass index, total cholesterol level, hypertension, diabetes, stroke and intracranial volume (only for volume measurements). Effect sizes for eGFR and ACR were normalized to their interquartile range (IQR).

Results

Higher levels of UACR and lower levels of eGFR were associated with reduced brain volume in regions typically affected by Alzheimer’s Dementia (AD), such as the hippocampus, and in non-AD related regions. Higher UACR and lower eGFR were also associated with increased WMH volume, and higher number of micro-hemorrhages and infarcts. The magnitude of the observed associations with MRI brain pathologies was similar between UACR and eGFR.

Conclusion

Higher UACR and lower eGFR are strongly associated with brain structural MRI abnormalities. These abnormalities include white matter lesions, infarcts, microhemorrhages and signs of brain atrophy, which manifest globally in regions typical for AD as well as other brain regions.

Pathology in brain MRICystatin-based eGFR
per 1-IQR decrease
Log UACR
per 1-IQR increase
Standardized beta coefficient (95%CI)1p-valueStandardized beta coefficient (95%CI)1p-value
Brain volume, AD signature region-0.10 (-0.14 to -0.05)<0.001-0.07 (-0.11 to -0.04)<0.001
Brain volume, non-AD signature region-0.05 (-0.08 to -0.02)0.003-0.05 (-0.07 to -0.02)0.001
Log WMH volume0.11 (0.04 to 0.17)0.0010.10 (0.05 to 0.16)<0.001
 Odds ratio (95%CI)2 Odds ratio (95%CI)2 
Brain micro-hemorrhages1.14 (0.96 to 1.36)0.141.22 (1.07 to 1.40)0.003
Brain infarcts1.21 (1.02 to 1.45)0.0331.33 (1.16 to 1.52)<0.001
Table: Adjusted estimates for associations of eGFR and ACR with MRI brain pathological changes
AD: Alzheimer's disease
WMH: White matter hyperintensity
1Estimates from linear regression models including age, sex, race, education, Apolipoprotein E4 level, smoking, body mass index, total cholesterol level, hypertension, diabetes, stroke and intracranial volume as covariates
2Estimates from logistic regression models including age, sex, race, education, Apolipoprotein E4 level, smoking, body mass index, total cholesterol level, hypertension, diabetes and stroke as covariates

Funding

  • Other NIH Support