Cardiovascular risks impact human brain Nacetylaspartate in regionally specific patterns

Joshua Chiappelli, Laura M. Rowland, S. Andrea Wijtenburg, Hongji Chen, Andrew A. Maudsley, Sulaiman Sheriff, Shuo Chen, Anya Savransky, Wyatt Marshall, Meghann C. Ryan, Heather A. Bruce, Alan R. Shuldiner, Braxton D. Mitchell, Peter Kochunov, L. Elliot Hong

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Cardiovascular risk factors such as dyslipidemia and hypertension increase the risk for white matter pathology and cognitive decline. We hypothesize that white matter levels of N-acetylaspartate (NAA), a chemical involved in the metabolic pathway for myelin lipid synthesis, could serve as a biomarker that tracks the influence of cardiovascular risk factors on white matter prior to emergence of clinical changes. To test this, we measured levels of NAA across white matter and gray matter in the brain using echo planar spectroscopic imaging (EPSI) in 163 individuals and examined the relationship of regional NAA levels and cardiovascular risk factors as indexed by the Framingham Cardiovascular Risk Score (FCVRS). NAA was strongly and negatively correlated with FCVRS across the brain, but, after accounting for age and sex, the association was found primarily in white matter regions, with additional effects found in the thalamus, hippocampus, and cingulate gyrus. FCVRS was also negatively correlated with creatine levels, again primarily in white matter. The results suggest that cardiovascular risks are related to neurochemistry with a predominantly white matter pattern and some subcortical and cortical gray matter involvement. NAA mapping of the brain may provide early surveillance for the potential subclinical impact of cardiovascular and metabolic risk factors on the brain.

Original languageEnglish (US)
Pages (from-to)25243-25249
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number50
StatePublished - Dec 10 2019


  • Creatine
  • Hypertension
  • Neurochemistry
  • White matter

ASJC Scopus subject areas

  • General


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