Published Online
on January 4, 2007

A more recent version of this article appeared on February 1, 2007

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Submitted on July 27, 2006
Revised on August 29, 2006
Accepted on September 13, 2006

Endothelial Function and White Matter Hyperintensities in Older Adults With Cardiovascular Disease

Karin F. Hoth PhD^*; David F. Tate PhD; Athena Poppas MD; Daniel E. Forman MD; John Gunstad PhD; David J. Moser PhD; Robert H. Paul PhD; Angela L. Jefferson PhD; Andreana P. Haley PhD; and Ronald A. Cohen PhD

From Department of Psychiatry and Human Behavior (K.F.H., D.F.T., A.P.H., R.A.C.), Brown Medical School, Providence, RI; Department of Cardiology (A.P.), Brown Medical School, Providence, RI; Division of Cardiology (D.E.F.), Brigham and Women’s Hospital, Boston, Mass; Geriatric Research, Education, and Clinical Care (D.E.F.), VAMC of Boston, Boston, Mass; Harvard Medical School, Boston, Mass; Department of Psychology (J.G.), Kent State University, Kent, Ohio; Department of Psychiatry (D.J.M.), University of Iowa Carver College of Medicine, Iowa City, Iowa; Department of Psychology (R.H.P.), Behavioral Neuroscience, University of Missouri, St. Louis, St. Louis, Mo; Department of Neurology (A.L.J., Alzheimer’s Disease Center, Boston University School of Medicine, Boston, Mass.

^* To whom correspondence should be addressed. E-mail: Karin_Hoth{at}Brown.edu.

Background and Purpose--The presence of white matter hyperintensities on brain MRI is common among elderly individuals. Previous research suggests that cardiovascular risk factors are associated with increased white matter hyperintensities. Examining the role of direct physiological measures of vascular function will help to clarify the vascular mechanisms related to white matter hyperintensities. The aim of the present study was to examine the association between endothelial-dependent and endothelial-independent vasodilatation and white matter hyperintensity volume.

Methods--Twenty-five older adults with a range of cardiovascular diseases underwent brain MRI and completed assessments of blood vessel integrity using endothelial-dependent and independent flow-mediated dilation of the brachial artery. A semi-automated pixel-based method was used to quantify total brain volume and white matter hyperintensity volume, with white matter hyperintensity volume corrected for total brain volume. The association between measures of flow-mediated dilation and log-transformed white matter hyperintensities was examined.

Results--Correlation analysis revealed that endothelial-dependent vasodilatation was significantly and inversely associated with white matter hyperintensity volume. In contrast, endothelial-independent vasodilatation was not associated with white matter hyperintensities. Neither endothelial-dependent nor endothelial-independent vasodilatation was associated with total brain volume.

Conclusions--These data provide preliminary evidence that the integrity of the vascular endothelium is associated with white matter hyperintensities in older adults with cardiovascular disease. Impaired vascular function may be one mechanism that contributes to the development of white matter hyperintensities in the brain. Additional longitudinal research combining measures of vessel function, neuroimaging and cognition will be helpful in clarifying this potential mechanism.

Key words: cardiovascular disease • endothelium • magnetic resonance • white matter disease

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