[IC-P-046]: DIABETES-ASSOCIATED AMYLIN DYSHOMEOSTASIS PROVOKES BRAIN WHITE MATTER DISEASE AND BEHAVIOR CHANGES: AN ANIMAL MODEL

Age-related brain white matter disease is a form of small vessel disease (SVD) that may be associated with lacunar and other small subcortical infarcts, cerebral microbleeds, and perivascular spaces. This common form of cerebrovascular disease may manifest clinically as cognitive impairment of varying degrees and difficulty with mobility. Whereas some persons show cognitive decline and mobility failure when there are brain white matter hyperintensities (WMH) and acute stroke, others recover, and not everyone with brain white matter disease is disabled. Thus, repair or compensation of brain white matter may be possible, and furthermore, certain vascular risks, such as raised blood pressure, are targets for prevention of white matter disease or are administered to reduce the burden of such disease. Vascular risk modification may be useful, but alone may not be sufficient to prevent white matter disease progression. In this chapter, we specifically focus on WMH of vascular origin and explore white matter development, plasticity, and enduring processes of myelination across the health span in the context of experimental and human data, and compare and contrast resilient brain white matter propensity to a diseased white matter state. We conclude with thoughts on novel ways one might study white matter resilience, and predict future healthy cognitive and functional outcomes.

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Abstract MP078: Endothelial Function and Arterial Stiffness Associated with the Extent of Brain White Matter Disease

Circulation ◽

10.1161/circ.125.suppl_10.amp078 ◽

2012 ◽

Vol 125 (suppl_10) ◽

Author(s):

Dhananjay Vaidya ◽

Paul Nyquist ◽

Brian G Kral ◽

Lisa R Yanek ◽

Taryn F Moy ◽

...

Keyword(s):

White Matter ◽

Endothelial Function ◽

Brachial Artery ◽

Mixed Model ◽

Magnetic Resonance Images ◽

White Matter Disease ◽

Lesion Volume ◽

Brain White Matter ◽

Vascular Origin ◽

The Brain

Background: Subclinical white matter disease of the brain is presumed to be of vascular origin. However associations with important facets of arterial structure and function have not been well studied. Methods: We examined 381 participants in GeneSTAR (57% female, 63% white, 37% black, age 51.6±10.5), a study of subclinical vascular disease in apparently asymptomatic individuals from families with early coronary artery disease (CAD). Volumetric measurement of white matter hyperintensities (lesion volume as a percent of brain volume, WMHV) was acquired from T3 magnetic resonance images. Ultrasound imaging of the brachial artery at rest and during hyperemia induced by 5 minutes of forearm ischemia was used to determine (1) the distensibility coefficient (DC) of the brachial artery at rest and (2) endothelial function as the percentage hyperemic flow mediated dilation (FMD). Mixed model analyses correcting for intrafamilial correlations, adjusting for age, sex, race, total and HDL-cholesterol, diabetes, hypertension, and current smoking, was used to test the association of WMHV with DC and FMD. Results: The unadjusted Spearman correlation of WMHV with FMD was -0.19 (p<0.001) and with DC was -0.11 (p=0.030). In adjusted analysis, every 10% higher FMD was associated with 0.1% lower WMHV (p=0.028) and every 10% higher DC was associated with 3.3% lower WMHV (p=0.025). When both arterial measures were included in the same regression model, the association of FMD remained significant (p=0.037), while DC remained at the borderline (p=0.052). Conclusion: Two different facets of arterial function, (a) distensibility at rest, which is a material property of vessel walls, and (b) endothelial function resulting in functional reactivity to stimuli, are independently associated with subclinical white matter disease in the brain. This study reinforces the contention that white matter disease of the brain is of vascular origin.

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