Low cerebral blood flow is associated with lower memory function in metabolic syndrome

Authors

  • Alex C. Birdsill,

    1. Geriatric Research, Education and Clinical Center (GRECC), William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin, USA
    2. Department of Medicine, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin, USA
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  • Cynthia M. Carlsson,

    1. Geriatric Research, Education and Clinical Center (GRECC), William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin, USA
    2. Department of Medicine, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin, USA
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  • Auriel A. Willette,

    1. National Institute on Aging, Baltimore, Maryland, USA
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  • Ozioma C. Okonkwo,

    1. Geriatric Research, Education and Clinical Center (GRECC), William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin, USA
    2. Department of Medicine, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin, USA
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  • Sterling C. Johnson,

    1. Geriatric Research, Education and Clinical Center (GRECC), William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin, USA
    2. Department of Medicine, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin, USA
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  • Guofan Xu,

    1. Geriatric Research, Education and Clinical Center (GRECC), William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin, USA
    2. Department of Medicine, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin, USA
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  • Jennifer M. Oh,

    1. Geriatric Research, Education and Clinical Center (GRECC), William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin, USA
    2. Department of Medicine, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin, USA
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  • Catherine L. Gallagher,

    1. Department of Medicine, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin, USA
    2. William S. Middleton Memorial V. A. Hospital, Madison, Wisconsin, USA
    3. Department of Neurology, University of Wisconsin, Madison, Wisconsin, USA
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  • Rebecca L. Koscik,

    1. Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
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  • Erin M. Jonaitis,

    1. Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
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  • Bruce P. Hermann,

    1. Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
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  • Asenath LaRue,

    1. Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
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  • Howard A. Rowley,

    1. Department of Medicine, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin, USA
    2. University of Wisconsin School of Medicine and Public Health, Department of Radiology, Madison, Wisconsin, USA
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  • Sanjay Asthana,

    1. Geriatric Research, Education and Clinical Center (GRECC), William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin, USA
    2. Department of Medicine, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin, USA
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  • Mark A. Sager,

    1. Department of Medicine, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin, USA
    2. Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
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  • Barbara B. Bendlin

    Corresponding author
    1. Department of Medicine, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin, USA
    • Geriatric Research, Education and Clinical Center (GRECC), William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin, USA
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  • Disclosure: The authors declared no competing financial interests.

  • Funding sources: This project was supported by the Alzheimer's Association, NIRG-09-132626, and in part by the National Institute on Aging (R01 AG027161 [MAS], ADRC P50 AG033514 [SA]), and the University of Wisconsin Institute for Clinical and Translational Research, funded through a National Center for Research Resources/National Institutes of Health Clinical and Translational Science Award, 1UL1RR025011. The project was also facilitated by the facilities and resources at the Geriatric Research, Education, and Clinical Center (GRECC) of the William S. Middleton Memorial Veterans Hospital, Madison, WI. GRECC MS # 2012-10. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Correspondence: Barbara B. Bendlin (bbb@medicine.wisc.edu)

Abstract

Background

Metabolic syndrome (MetS)—a cluster of cardiovascular risk factors—is linked with cognitive decline and dementia. However, the brain changes underlying this link are presently unknown. In this study, we tested the relationship between MetS, cerebral blood flow (CBF), white matter hyperintensity burden, and gray matter (GM) volume in cognitively healthy late middle-aged adults. Additionally, the extent to which MetS was associated with cognitive performance was assessed.

Design and Methods

Late middle-aged adults from the Wisconsin Registry for Alzheimer's Prevention (N = 69, mean age = 60.4 years) underwent a fasting blood draw, arterial spin labeling perfusion MRI, T1-weighted MRI, T2FLAIR MRI, and neuropsychological testing. MetS was defined as abnormalities on three or more factors, including abdominal obesity, triglycerides, HDL-cholesterol, blood pressure, and fasting glucose.

Results

Mean GM CBF was 15% lower in MetS compared to controls. Voxel-wise image analysis indicated that the MetS group had lower CBF across a large portion of the cortical surface, with the exception of medial and inferior parts of the occipital and temporal lobes. The MetS group also had lower immediate memory function; a mediation analysis indicated this relationship was partially mediated by CBF. Among the MetS factors, abdominal obesity and elevated triglycerides were most strongly associated with lower CBF.

Conclusions

The results underscore the importance of reducing the number of cardiovascular risk factors for maintaining CBF and cognition in an aging population.

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