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Gray & white matter tissue contrast differentiates Mild Cognitive Impairment converters from non-converters

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Abstract

The clinical relevance of gray/white matter contrast ratio (GWR) in mild cognitive impairment (MCI) remains unknown. This study examined baseline GWR and 3-year follow-up diagnostic status in MCI. Alzheimer’s Disease Neuroimaging Initiative MCI participants with baseline 1.5 T MRI and 3-year follow-up clinical data were included. Participants were categorized into two groups based on 3-year follow-up diagnoses: 1) non-converters (n = 69, 75 ± 7, 26 % female), and 2) converters (i.e., dementia at follow-up; n = 69, 75 ± 7, 30 % female) who were matched on baseline age and Mini-Mental State Examination scores. Groups were compared on FreeSurfer generated baseline GWR from structural images in which higher values represent greater tissue contrast. A general linear model, adjusting for APOE-status, scanner type, hippocampal volume, and cortical thickness, revealed that converters evidenced lower GWR values than non-converters (i.e., more degradation in tissue contrast; p = 0.03). Individuals with MCI who convert to dementia have lower baseline GWR values than individuals who remain diagnostically stable over a 3-year period, statistically independent of cortical thickness or hippocampal volume.

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Acknowledgments

This research was supported by K23-AG030962 (Paul B. Beeson Career Development Award in Aging; ALJ); Alzheimer’s Association IIRG-08-88733 (ALJ); R01-AG034962 (ALJ); R01-HL111516 (ALJ); K24-AG046373 (ALJ); American Federation for Aging Research Medical Student Training in Aging Research Grant (JS; T35-AG038027); R01-NR010827 (DS); and the Vanderbilt Memory & Alzheimer’s Center. Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, by the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec, Inc.; Bristol-Myers Squibb Company; Eisai, Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development, LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer, Inc.; Servier; Synarc, Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Disease Cooperative Study Rev October 16, 2012 at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129 and K01 AG030514.

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Authors and Affiliations

  1. Vanderbilt Memory & Alzheimer’s Center, Department of Neurology, Vanderbilt University Medical Center, 2525 West End Avenue, 12th Floor – Suite 1200, Nashville, TN, 37203, USA

    Angela L. Jefferson, Katherine A. Gifford, Stephen Damon & G. William Chapman IV

  2. Boston University School of Medicine, Boston, MA, USA

    Jamie Sparling

  3. Neuroimaging Research for Veteran’s Center, VA Boston Healthcare System, Boston, MA, USA

    Vitaly Dobromyslin & David Salat

  4. Department of Biostatistics, Vanderbilt University, Nashville, TN, USA

    Dandan Liu

  5. Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA

    David Salat

  6. Department of Radiology, Massachusetts General Hospital, Boston, MA, USA

    David Salat

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  1. Angela L. Jefferson
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  2. Katherine A. Gifford
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for the Alzheimer’s Disease Neuroimaging Initiative

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Correspondence to Angela L. Jefferson.

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Stephen Damon and Dandan Liu completed statistical analysis.

Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.ucla.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.ucla.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

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Jefferson, A.L., Gifford, K.A., Damon, S. et al. Gray & white matter tissue contrast differentiates Mild Cognitive Impairment converters from non-converters. Brain Imaging and Behavior 9, 141–148 (2015). https://doi.org/10.1007/s11682-014-9291-2

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