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April 19, 2016; 86 (16) Article

Brain arterial aging and its relationship to Alzheimer dementia

Jose Gutierrez, Lawrence Honig, Mitchell S.V. Elkind, Jay P. Mohr, James Goldman, Andrew J. Dwork, Susan Morgello, Randolph S. Marshall
First published March 16, 2016, DOI: https://doi.org/10.1212/WNL.0000000000002590
Jose Gutierrez
From the Departments of Neurology (J.G., L.H., M.S.V.E., J.P.M.) and Psychiatry (A.J.D.), College of Physicians and Surgeons, Department of Epidemiology, Mailman School of Public Health (M.S.V.E., R.S.M.), and Department of Pathology and Cell Biology (J.G., A.J.D.), Columbia University; Division of Molecular Imaging and Neuropathology (A.J.D.), New York State Psychiatric Institute; and the Departments of Neurology, Neuroscience, and Pathology (S.M.), Icahn School of Medicine at Mount Sinai, New York, NY.
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Lawrence Honig
From the Departments of Neurology (J.G., L.H., M.S.V.E., J.P.M.) and Psychiatry (A.J.D.), College of Physicians and Surgeons, Department of Epidemiology, Mailman School of Public Health (M.S.V.E., R.S.M.), and Department of Pathology and Cell Biology (J.G., A.J.D.), Columbia University; Division of Molecular Imaging and Neuropathology (A.J.D.), New York State Psychiatric Institute; and the Departments of Neurology, Neuroscience, and Pathology (S.M.), Icahn School of Medicine at Mount Sinai, New York, NY.
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Mitchell S.V. Elkind
From the Departments of Neurology (J.G., L.H., M.S.V.E., J.P.M.) and Psychiatry (A.J.D.), College of Physicians and Surgeons, Department of Epidemiology, Mailman School of Public Health (M.S.V.E., R.S.M.), and Department of Pathology and Cell Biology (J.G., A.J.D.), Columbia University; Division of Molecular Imaging and Neuropathology (A.J.D.), New York State Psychiatric Institute; and the Departments of Neurology, Neuroscience, and Pathology (S.M.), Icahn School of Medicine at Mount Sinai, New York, NY.
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Jay P. Mohr
From the Departments of Neurology (J.G., L.H., M.S.V.E., J.P.M.) and Psychiatry (A.J.D.), College of Physicians and Surgeons, Department of Epidemiology, Mailman School of Public Health (M.S.V.E., R.S.M.), and Department of Pathology and Cell Biology (J.G., A.J.D.), Columbia University; Division of Molecular Imaging and Neuropathology (A.J.D.), New York State Psychiatric Institute; and the Departments of Neurology, Neuroscience, and Pathology (S.M.), Icahn School of Medicine at Mount Sinai, New York, NY.
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James Goldman
From the Departments of Neurology (J.G., L.H., M.S.V.E., J.P.M.) and Psychiatry (A.J.D.), College of Physicians and Surgeons, Department of Epidemiology, Mailman School of Public Health (M.S.V.E., R.S.M.), and Department of Pathology and Cell Biology (J.G., A.J.D.), Columbia University; Division of Molecular Imaging and Neuropathology (A.J.D.), New York State Psychiatric Institute; and the Departments of Neurology, Neuroscience, and Pathology (S.M.), Icahn School of Medicine at Mount Sinai, New York, NY.
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Andrew J. Dwork
From the Departments of Neurology (J.G., L.H., M.S.V.E., J.P.M.) and Psychiatry (A.J.D.), College of Physicians and Surgeons, Department of Epidemiology, Mailman School of Public Health (M.S.V.E., R.S.M.), and Department of Pathology and Cell Biology (J.G., A.J.D.), Columbia University; Division of Molecular Imaging and Neuropathology (A.J.D.), New York State Psychiatric Institute; and the Departments of Neurology, Neuroscience, and Pathology (S.M.), Icahn School of Medicine at Mount Sinai, New York, NY.
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Susan Morgello
From the Departments of Neurology (J.G., L.H., M.S.V.E., J.P.M.) and Psychiatry (A.J.D.), College of Physicians and Surgeons, Department of Epidemiology, Mailman School of Public Health (M.S.V.E., R.S.M.), and Department of Pathology and Cell Biology (J.G., A.J.D.), Columbia University; Division of Molecular Imaging and Neuropathology (A.J.D.), New York State Psychiatric Institute; and the Departments of Neurology, Neuroscience, and Pathology (S.M.), Icahn School of Medicine at Mount Sinai, New York, NY.
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Randolph S. Marshall
From the Departments of Neurology (J.G., L.H., M.S.V.E., J.P.M.) and Psychiatry (A.J.D.), College of Physicians and Surgeons, Department of Epidemiology, Mailman School of Public Health (M.S.V.E., R.S.M.), and Department of Pathology and Cell Biology (J.G., A.J.D.), Columbia University; Division of Molecular Imaging and Neuropathology (A.J.D.), New York State Psychiatric Institute; and the Departments of Neurology, Neuroscience, and Pathology (S.M.), Icahn School of Medicine at Mount Sinai, New York, NY.
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Citation
Brain arterial aging and its relationship to Alzheimer dementia
Jose Gutierrez, Lawrence Honig, Mitchell S.V. Elkind, Jay P. Mohr, James Goldman, Andrew J. Dwork, Susan Morgello, Randolph S. Marshall
Neurology Apr 2016, 86 (16) 1507-1515; DOI: 10.1212/WNL.0000000000002590

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Abstract

Objective: To test the hypothesis that brain arterial aging is associated with the pathologic diagnosis of Alzheimer disease (AD).

Methods: Brain large arteries were assessed for diameter, gaps in the internal elastic lamina (IEL), luminal stenosis, atherosclerosis, and lumen-to-wall ratio. Elastin, collagen, and amyloid were assessed with Van Gieson, trichrome, and Congo red staining intensities, and quantified automatically. Brain infarcts and AD (defined pathologically) were assessed at autopsy. We created a brain arterial aging (BAA) score with arterial characteristics associated with aging after adjusting for demographic and clinical variables using cross-sectional generalized linear models.

Results: We studied 194 autopsied brains, 25 (13%) of which had autopsy evidence of AD. Brain arterial aging consisted of higher interadventitial and lumen diameters, thickening of the wall, increased prevalence of IEL gaps, concentric intima thickening, elastin loss, increased amyloid deposition, and a higher IEL proportion without changes in lumen-to-wall ratio. In multivariable analysis, a high IEL proportion (B = 1.96, p = 0.030), thick media (B = 3.50, p = 0.001), elastin loss (B = 6.16, p < 0.001), IEL gaps (B = 3.14, p = 0.023), and concentric intima thickening (B = 7.19, p < 0.001) were used to create the BAA score. Adjusting for demographics, vascular risk factors, atherosclerosis, and brain infarcts, the BAA score was associated with AD (B = 0.022, p = 0.002).

Conclusions: Aging of brain large arteries is characterized by arterial dilation with a commensurate wall thickening, elastin loss, and IEL gaps. Greater intensity of arterial aging was associated with AD independently of atherosclerosis and brain infarcts. Understanding the drivers of arterial aging may advance the knowledge of the pathophysiology of AD.

GLOSSARY

AD=
Alzheimer disease;
BAA=
brain arterial aging;
CERAD=
Consortium to Establish a Registry for Alzheimer's Disease;
EVG=
elastic Van Gieson;
IEL=
internal elastic lamina;
IQR=
interquartile range

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received July 31, 2015.
  • Accepted in final form January 8, 2016.
  • © 2016 American Academy of Neurology
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