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A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis
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Cerebrovascular Damage Mediates Relations Between Aortic Stiffness and Memory.

Leroy L Cooper1, Todd Woodard1, Sigurdur Sigurdsson1

  • 1From the Cardiovascular Engineering, Inc, Norwood, MA (L.L.C., T.W., A.A.T., G.F.M.); Cardiovascular Research Center, Rhode Island Hospital, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Icelandic Heart Association, Kopavogur, Iceland (S.S., T.A., G.E., V.G.); Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands (M.A.B.); Division of Nephrology and Department of Medicine, Tufts Medical Center, Boston, MA (L.A.I.); Faculty of Medicine, University of Iceland, Reykjavik, Iceland (T.A., V.G.); and Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, MD (T.B.H., L.J.L.).

Hypertension (Dallas, Tex. : 1979)
|November 18, 2015
PubMed
Summary

Aortic stiffness, measured by carotid-femoral pulse wave velocity, is linked to poorer memory in older adults. This association is partly explained by changes in brain blood vessels and damage from small vessel disease.

Keywords:
cognitiondementiahemodynamicsmemoryvascular stiffness

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Area of Science:

  • Cardiovascular Health
  • Neuroscience
  • Gerontology

Background:

  • Aortic stiffness is a known risk factor for cognitive decline.
  • Cerebrovascular changes and small vessel disease are implicated in cognitive impairment.

Purpose of the Study:

  • To investigate the association between aortic stiffness (carotid-femoral pulse wave velocity) and cognitive function, specifically memory.
  • To explore whether cerebrovascular remodeling and parenchymal small vessel disease mediate this relationship.

Main Methods:

  • Analysis of 1820 participants from the Age, Gene/Environment Susceptibility-Reykjavik Study.
  • Multivariable linear regression models adjusted for confounders.
  • Assessment of carotid-femoral pulse wave velocity, cerebrovascular resistance, white matter hyperintensities, and memory scores.

Main Results:

  • Higher carotid-femoral pulse wave velocity was significantly associated with lower memory scores (P=0.002).
  • Cerebrovascular resistance and white matter hyperintensities mediated the relationship between aortic stiffness and memory, explaining approximately 41% of the effect.
  • The direct effect of aortic stiffness on memory was attenuated when mediators were included.

Conclusions:

  • Aortic stiffness is associated with impaired memory in older adults.
  • Cerebral microvascular remodeling and microvascular parenchymal damage are key mediating pathways in this association.