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ABSTRACT

Objectives:

To investigate whether severity and progression of periventricular and deep white matter lesions (WML) and lacunar infarcts were associated with progression of brain atrophy.

Methods:

Within the SMART-MR study, a prospective cohort on MRI changes in patients with symptomatic atherosclerotic disease, 565 patients (57 ± 9 years) without large infarcts had vascular screening and 1.5 T MRI at baseline and after a mean follow-up of 3.9 years. With automated brain segmentation, total brain, cortical gray matter, ventricular, and WML volumes were estimated and expressed relative to intracranial volume (%). Lacunar infarcts were rated manually.

Results:

Using linear regression analyses adjusted for demographics and vascular risk factors, periventricular WML volume at baseline was associated with greater decrease in cortical gray matter volume (B = −1.73%, 95% confidence interval [CI] −3.15% to −0.30%, per 1% WML volume increase) and greater increase in ventricular volume (B = 0.12%, 95% CI 0.04% to 0.20%). Progression of periventricular WML volume corresponded with a greater decrease in cortical gray matter volume (B = −0.45%, 95% CI −0.9% to 0%) and greater increase in ventricular volume (B = 0.15%, 95% CI 0.1% to 0.2%). Presence of lacunar infarcts was associated with greater decline in total brain volume (B = −0.25%, 95% CI −0.49% to −0.01%) and progression of lacunar infarcts with a greater decrease of total brain (B = −0.30%, 95% CI −0.59% to 0.01%) and cortical gray matter volume (B = −0.81%, 95% CI −1.43% to −0.20%).

Conclusions:

In patients with symptomatic atherosclerotic disease, presence and progression of periventricular WML and lacunar infarcts is associated with greater progression of brain atrophy independent of vascular risk factors.

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Supplementary Material

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Information & Authors

Information

Published In

Neurology®
Volume 79Number 20November 13, 2012
Pages: 2029-2036
PubMed: 23115210

Publication History

Received: April 4, 2012
Accepted: July 19, 2012
Published online: October 31, 2012
Published in print: November 13, 2012

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Disclosure

R.P. Kloppenborg, P.J. Nederkoorn, A.M. Grool, K.L. Vincken, W.P.T.M. Mali, and M. Vermeulen report no disclosures. Y. van der Graaf obtained funding through a program grant from The Netherlands Organization for Scientific Research-Medical Sciences (NWO-MW: project no. 904-65-095). M.I. Geerlings obtained funding through a grant from the Netherlands Organization for Scientific Research (NWO: project no. 917-66-311). Go to Neurology.org for full disclosures.

Authors

Affiliations & Disclosures

R.P. Kloppenborg, MD
From the Department of Neurology (R.P.K., P.J.N., M.V.), Academic Medical Center, Amsterdam; and Julius Center for Health Sciences and Primary Care (R.P.K., A.M.G., Y.v.d.G., M.I.G.), Image Sciences Institute (K.L.V.), and Department of Radiology (W.P.T.M.M.), University Medical Center Utrecht, Utrecht, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
P.J. Nederkoorn, MD, PhD
From the Department of Neurology (R.P.K., P.J.N., M.V.), Academic Medical Center, Amsterdam; and Julius Center for Health Sciences and Primary Care (R.P.K., A.M.G., Y.v.d.G., M.I.G.), Image Sciences Institute (K.L.V.), and Department of Radiology (W.P.T.M.M.), University Medical Center Utrecht, Utrecht, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
A.M. Grool, MD
From the Department of Neurology (R.P.K., P.J.N., M.V.), Academic Medical Center, Amsterdam; and Julius Center for Health Sciences and Primary Care (R.P.K., A.M.G., Y.v.d.G., M.I.G.), Image Sciences Institute (K.L.V.), and Department of Radiology (W.P.T.M.M.), University Medical Center Utrecht, Utrecht, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Grant from the Netherlands Heart Foundation (NHF project 2007B027)
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
K.L. Vincken, PhD
From the Department of Neurology (R.P.K., P.J.N., M.V.), Academic Medical Center, Amsterdam; and Julius Center for Health Sciences and Primary Care (R.P.K., A.M.G., Y.v.d.G., M.I.G.), Image Sciences Institute (K.L.V.), and Department of Radiology (W.P.T.M.M.), University Medical Center Utrecht, Utrecht, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
W.P.T.M. Mali, MD, PhD
From the Department of Neurology (R.P.K., P.J.N., M.V.), Academic Medical Center, Amsterdam; and Julius Center for Health Sciences and Primary Care (R.P.K., A.M.G., Y.v.d.G., M.I.G.), Image Sciences Institute (K.L.V.), and Department of Radiology (W.P.T.M.M.), University Medical Center Utrecht, Utrecht, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
M. Vermeulen, MD, PhD
From the Department of Neurology (R.P.K., P.J.N., M.V.), Academic Medical Center, Amsterdam; and Julius Center for Health Sciences and Primary Care (R.P.K., A.M.G., Y.v.d.G., M.I.G.), Image Sciences Institute (K.L.V.), and Department of Radiology (W.P.T.M.M.), University Medical Center Utrecht, Utrecht, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Y. van der Graaf, MD, PhD
From the Department of Neurology (R.P.K., P.J.N., M.V.), Academic Medical Center, Amsterdam; and Julius Center for Health Sciences and Primary Care (R.P.K., A.M.G., Y.v.d.G., M.I.G.), Image Sciences Institute (K.L.V.), and Department of Radiology (W.P.T.M.M.), University Medical Center Utrecht, Utrecht, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
M.I. Geerlings, PhD
From the Department of Neurology (R.P.K., P.J.N., M.V.), Academic Medical Center, Amsterdam; and Julius Center for Health Sciences and Primary Care (R.P.K., A.M.G., Y.v.d.G., M.I.G.), Image Sciences Institute (K.L.V.), and Department of Radiology (W.P.T.M.M.), University Medical Center Utrecht, Utrecht, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Journal of Alzheimer's disease, Associate Editor, 2012
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
Netherlands Organisation for Scientific Research (NWO), project No. 917-66-311, principal investigator, 2006-2012
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
On behalf of the SMART Study Group
From the Department of Neurology (R.P.K., P.J.N., M.V.), Academic Medical Center, Amsterdam; and Julius Center for Health Sciences and Primary Care (R.P.K., A.M.G., Y.v.d.G., M.I.G.), Image Sciences Institute (K.L.V.), and Department of Radiology (W.P.T.M.M.), University Medical Center Utrecht, Utrecht, the Netherlands.

Notes

Correspondence & reprint requests to Dr. Geerlings: [email protected]
Coinvestigators of the SMART Study Group are listed on the Neurology® Web site at www.neurology.org.
Study funding: NWO-MW: project no. 904-65-095 and project no. 917-66-311.
Go to Neurology.org for full disclosures. Disclosures deemed relevant by the authors, if any, are provided at the end of this article.

Author Contributions

R.P. Kloppenborg participated in drafting/revising the manuscript, study concept, and analysis of the data, and completed the statistical analysis. P.J. Nederkoorn participated in the drafting/revising of the manuscript. A.M. Grool participated in the drafting/revising of the manuscript and the acquisition and analysis of the data. K.L. Vincken contributed to the study with vital tools and the acquisition of the data. W.P.T.M. Mali contributed to drafting/revising the manuscript and supervising/coordinating the study. M. Vermeulen participated in drafting/revising the manuscript. Y. van der Graaf contributed to drafting/revising the manuscript and supervising/coordinating the study. M.I. Geerlings participated in drafting/revising the manuscript, study concept and analysis of the data, and supervised/coordinated the study.

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