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August 27, 2019; 93 (9) Article

Adiposity is related to cerebrovascular and brain volumetry outcomes in the RUN DMC study

Ilse A.C. Arnoldussen, Deborah R. Gustafson, Esther M.C. Leijsen, Frank-Erik de Leeuw, Amanda J. Kiliaan
First published July 30, 2019, DOI: https://doi.org/10.1212/WNL.0000000000008002
Ilse A.C. Arnoldussen
From the Departments of Anatomy (I.A.C.A., A.J.K.) and Neurology (E.M.C.L., F.-E.d.L.), Donders Institute for Brain, Cognition and Behaviour, and Radboud Alzheimer Center (I.A.C.A., A.J.K.), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Neurology (D.R.G.), The State University of New York Downstate Health Sciences University, Brooklyn; and Department of Health and Education (D.R.G.), University of Skövde, Sweden.
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Deborah R. Gustafson
From the Departments of Anatomy (I.A.C.A., A.J.K.) and Neurology (E.M.C.L., F.-E.d.L.), Donders Institute for Brain, Cognition and Behaviour, and Radboud Alzheimer Center (I.A.C.A., A.J.K.), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Neurology (D.R.G.), The State University of New York Downstate Health Sciences University, Brooklyn; and Department of Health and Education (D.R.G.), University of Skövde, Sweden.
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Esther M.C. Leijsen
From the Departments of Anatomy (I.A.C.A., A.J.K.) and Neurology (E.M.C.L., F.-E.d.L.), Donders Institute for Brain, Cognition and Behaviour, and Radboud Alzheimer Center (I.A.C.A., A.J.K.), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Neurology (D.R.G.), The State University of New York Downstate Health Sciences University, Brooklyn; and Department of Health and Education (D.R.G.), University of Skövde, Sweden.
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Frank-Erik de Leeuw
From the Departments of Anatomy (I.A.C.A., A.J.K.) and Neurology (E.M.C.L., F.-E.d.L.), Donders Institute for Brain, Cognition and Behaviour, and Radboud Alzheimer Center (I.A.C.A., A.J.K.), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Neurology (D.R.G.), The State University of New York Downstate Health Sciences University, Brooklyn; and Department of Health and Education (D.R.G.), University of Skövde, Sweden.
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Amanda J. Kiliaan
From the Departments of Anatomy (I.A.C.A., A.J.K.) and Neurology (E.M.C.L., F.-E.d.L.), Donders Institute for Brain, Cognition and Behaviour, and Radboud Alzheimer Center (I.A.C.A., A.J.K.), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Neurology (D.R.G.), The State University of New York Downstate Health Sciences University, Brooklyn; and Department of Health and Education (D.R.G.), University of Skövde, Sweden.
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Adiposity is related to cerebrovascular and brain volumetry outcomes in the RUN DMC study
Ilse A.C. Arnoldussen, Deborah R. Gustafson, Esther M.C. Leijsen, Frank-Erik de Leeuw, Amanda J. Kiliaan
Neurology Aug 2019, 93 (9) e864-e878; DOI: 10.1212/WNL.0000000000008002

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Abstract

Objective Adiposity predictors, body mass index (BMI), waist circumference (WC), and blood leptin and total adiponectin levels were associated with components of cerebral small vessel disease (CSVD) and brain volumetry in 503 adults with CSVD who were ≥50 years of age and enrolled in the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC).

Methods RUN DMC participants were followed up for 9 years (2006–2015). BMI, WC, brain imaging, and dementia diagnoses were evaluated at baseline and follow-up. Adipokines were measured at baseline. Brain imaging outcomes included CSVD components, white matter hyperintensities, lacunes, microbleeds, gray and white matter, hippocampal, total brain, and intracranial volumes.

Results Cross-sectionally among men at baseline, higher BMI, WC, and leptin were associated with lower gray matter and total brain volumes, and higher BMI and WC were associated with lower hippocampal volume. At follow-up 9 years later, higher BMI was cross-sectionally associated with lower gray matter volume, and an obese WC (>102 cm) was protective for ≥1 lacune or ≥1 microbleed in men. In women, increasing BMI and overweight or obesity (BMI ≥25 kg/m2 or WC >88 cm) were associated with ≥1 lacune. Longitudinally, over 9 years, a baseline obese WC was associated with decreasing hippocampal volume, particularly in men, and increasing white matter hyperintensity volume in women and men.

Conclusions Anthropometric and metabolic adiposity predictors were differentially associated with CSVD components and brain volumetry outcomes by sex. Higher adiposity is associated with a vascular-neurodegenerative spectrum among adults at risk for vascular forms of cognitive impairment and dementias.

Glossary

BMI=
body mass index;
CSVD=
cerebral small vessel disease;
DSM-IV=
Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
FLAIR=
fluid-attenuated inversion recovery;
GMV=
gray matter volume;
HV=
hippocampal volume;
MMSE=
Mini–Mental State Examination;
RUN DMC=
Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort;
STRIVE=
Standards for Reporting and Imaging of Small Vessel Disease;
TBV=
total brain volume;
T2DM=
type 2 diabetes mellitus;
WC=
waist circumference;
WMH=
white matter hyperintensities;
WMV=
white matter volume

Footnotes

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

  • ↵* These authors contributed equally to this work.

  • Received September 21, 2018.
  • Accepted in final form April 8, 2019.
  • © 2019 American Academy of Neurology
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