Get access

Midlife measurements of white matter microstructure predict subsequent regional white matter atrophy in healthy adults

Authors

  • Martina Ly,

    1. Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin
    2. Department of Medicine, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin
    3. Neuroscience Training Program, University of Wisconsin, Madison, Wisconsin
    Search for more papers by this author
  • Elisa Canu,

    1. Laboratory of Epidemiology Neuroimaging and Telemedicine, IRCCS Centro San Giovanni di Dio FBF, The National Centre for Research and Care of Alzheimer's and Mental Diseases, Brescia, Italy
    Search for more papers by this author
  • Guofan Xu,

    1. Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin
    2. Department of Medicine, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin
    Search for more papers by this author
  • Jennifer Oh,

    1. Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin
    2. Department of Medicine, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin
    Search for more papers by this author
  • Donald G. McLaren,

    1. Harvard Medical School, Boston, Massachusetts
    2. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts
    3. Department of Radiology, Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts
    4. Geriatric Research Education and Clinical Center, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, Massachusetts
    Search for more papers by this author
  • N. Maritza Dowling,

    1. Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin
    2. Department of Medicine, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin
    3. Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, Wisconsin
    Search for more papers by this author
  • Andrew L. Alexander,

    1. Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
    2. Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
    3. Waisman Laboratory for Brain Imaging and Behavior, Madison, Wisconsin
    Search for more papers by this author
  • Mark A. Sager,

    1. Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin
    2. Department of Medicine, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin
    Search for more papers by this author
  • Sterling C. Johnson,

    1. Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin
    2. Department of Medicine, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin
    Search for more papers by this author
  • Barbara B. Bendlin

    Corresponding author
    1. Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin
    2. Department of Medicine, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin
    • Correspondence to: Barbara B. Bendlin, University of Wisconsin, School of Medicine and Public Health, Wisconsin Alzheimer's Disease Research Center, J5/1 Mezzanine, 600 Highland Avenue, Madison, WI 53792, USA. E-mail: bbb@medicine.wisc.edu

    Search for more papers by this author

Abstract

Objectives: Although age-related brain changes are becoming better understood, midlife patterns of change are still in need of characterization, and longitudinal studies are lacking. The aim of this study was to determine if baseline fractional anisotropy (FA), obtained from diffusion tensor imaging (DTI) predicts volume change over a 4-year interval. Experimental design: Forty-four cognitively healthy middle-age adults underwent baseline DTI and longitudinal T1-weighted magnetic resonance imaging. Tensor-based morphometry methods were used to evaluate volume change over time. FA values were extracted from regions of interest that included the cingulum, entorhinal white matter, and the genu and splenium of the corpus callosum. Baseline FA was used as a predictor variable, whereas gray and white matter atrophy rates as indexed by Tensor-based morphometry were the dependent variables. Principal observations: Over a 4-year period, participants showed significant contraction of white matter, especially in frontal, temporal, and cerebellar regions (P < 0.05, corrected for multiple comparisons). Baseline FA in entorhinal white matter, genu, and splenium was associated with longitudinal rates of atrophy in regions that included the superior longitudinal fasciculus, anterior corona radiata, temporal stem, and white matter of the inferior temporal gyrus (P < 0.001, uncorrected for multiple comparisons). Conclusions: Brain change with aging is characterized by extensive shrinkage of white matter. Baseline white matter microstructure as indexed by DTI was associated with some of the observed regional volume loss. The findings suggest that both white matter volume loss and microstructural alterations should be considered more prominently in models of aging and neurodegenerative diseases. Hum Brain Mapp 35:2044–2054, 2014. © 2013 Wiley Periodicals, Inc.

Get access to the full text of this article

Ancillary