Memory performance and fMRI signal in presymptomatic familial Alzheimer's disease

Authors

  • Meredith N. Braskie,

    Corresponding author
    1. Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California
    2. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California
    3. Laboratory of Neuro Imaging, David Geffen School of Medicine at UCLA, Los Angeles, California
    • Laboratory of Neuro Imaging, UCLA School of Medicine, 635 Charles E. Young Dr. South Suite 225, Los Angeles, CA 90095-7334. E-mail: mbraskie@ucla.edu

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  • Luis D. Medina,

    1. Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California
    2. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California
    Current affiliation:
    1. SDSU/UCSD Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA
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  • Yaneth Rodriguez-Agudelo,

    1. National Institute of Neurology and Neurosurgery, Mexico City, Mexico
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  • Daniel H. Geschwind,

    1. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California
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  • Miguel Angel Macias-Islas,

    1. Department of Neuroscience, University of Guadalajara, Mexico
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  • Paul M. Thompson,

    1. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California
    2. Laboratory of Neuro Imaging, David Geffen School of Medicine at UCLA, Los Angeles, California
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  • Jeffrey L. Cummings,

    1. Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California
    2. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California
    Current affiliation:
    1. Cleveland Clinic Lou Ruvo Center for Brain Health, Los Vegas, NV, USA
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  • Susan Y. Bookheimer,

    1. Semel Institute for Psychiatry and Human Behavior, UCLA, Los Angeles, California
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  • John M. Ringman

    1. Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California
    2. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California
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Abstract

Rare autosomal dominant mutations result in familial Alzheimer's disease (FAD) with a relatively consistent age of onset within families. This provides an estimate of years until disease onset (relative age) in mutation carriers. Increased AD risk has been associated with differences in functional magnetic resonance imaging (fMRI) activity during memory tasks, but most of these studies have focused on possession of apolipoprotein E allele 4 (APOE4), a risk factor, but not causative variant, of late-onset AD. Evaluation of fMRI activity in presymptomatic FAD mutation carriers versus noncarriers provides insight into preclinical changes in those who will certainly develop AD in a prescribed period of time. Adults from FAD mutation-carrying families (nine mutation carriers, eight noncarriers) underwent fMRI scanning while performing a memory task. We examined fMRI signal differences between carriers and noncarriers, and how signal related to fMRI task performance within mutation status group, controlling for relative age and education. Mutation noncarriers had greater retrieval period activity than carriers in several AD-relevant regions, including the left hippocampus. Better performing noncarriers showed greater encoding period activity including in the parahippocampal gyrus. Poorer performing carriers showed greater retrieval period signal, including in the frontal and temporal lobes, suggesting underlying pathological processes. Hum Brain Mapp 34:3308–3319, 2013. © 2012 Wiley Periodicals, Inc.

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