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VOXEL-WISE DETERMINATION OF SENSITIVITY, SPECIFICITY, AND THRESHOLDS FOR AMYLOID POSITIVITY USING [18F]FLORBETAPIR PET

  • Tharick A. Pascoal
    Affiliations
    Douglas Hospital Research Centre, Verdun, QC, Canada

    McGill University, Montreal, QC, Canada

    McGill University Research Centre for Studies in Aging, Verdun, QC, Canada

    Translational Neuroimaging Laboratory- McGill University, Verdun, QC, Canada

    Centre for Studies on Prevention of Alzheimer’s Disease (StoP-AD Centre), Douglas Mental Health Institute, Verdun, QC, Canada
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  • Sulantha S. Mathotaarachchi
    Affiliations
    McGill University, Montreal, QC, Canada

    McGill University Research Centre for Studies in Aging, Verdun, QC, Canada
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  • Monica Shin
    Affiliations
    McGill University Research Centre for Studies in Aging, Verdun, QC, Canada

    Translational Neuroimaging Laboratory- McGill University, Verdun, QC, Canada
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  • Min Su Kang
    Affiliations
    Translational Neuroimaging Laboratory- McGill University, Verdun, QC, Canada

    Douglas Mental Health Institute, Montreal, QC, Canada
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  • Kok Pin Ng
    Affiliations
    McGill University Research Centre for Studies in Aging, Verdun, QC, Canada

    National Neuroscience Institute, Singapore, Singapore
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  • Joseph Therriault
    Affiliations
    Translational Neuroimaging Laboratory- McGill University, Verdun, QC, Canada
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  • Hanne Struyfs
    Affiliations
    Translational Neuroimaging Laboratory- McGill University, Verdun, QC, Canada

    icometrix, Leuven, Belgium

    Reference Center for Biological Markers of Dementia (BIODEM), Antwerp, Belgium

    Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium

    Institute Born-Bunge, University of Antwerp, Antwerp, Belgium
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  • Jean-Paul Soucy
    Affiliations
    McGill University, Montreal, QC, Canada

    PERFORM Centre - Concordia University, Montréal, QC, Canada

    University of Montreal Hospital Centre, Montreal, QC, Canada
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  • Serge Gauthier
    Affiliations
    Douglas Hospital Research Centre, Verdun, QC, Canada

    McGill University Research Centre for Studies in Aging, Verdun, QC, Canada
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  • Pedro Rosa-Neto
    Affiliations
    Translational Neuroimaging Laboratory- McGill University, Verdun, QC, Canada

    Douglas Mental Health University Institute, Montreal, QC, Canada
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      Background

      Brain amyloid-β deposition is the core pathological feature of Alzheimer’s disease (AD) and can be detected in vivo using positron emission tomography (PET). However, the importance of the regional patterns of amyloid-β abnormality has been highly questioned due to its widespread deposition over the cortex. Here, using a novel analytical framework free of conceptual assumptions, we assess the regional patterns of amyloid-β deposition that are associated with AD dementia.

      Methods

      We assessed 211 control, 311 mild cognitive impairment, and 79 AD individuals who underwent [18F]florbetapir PET at baseline as well as clinical assessments at baseline and at 2 years. Receiver operating characteristic curves, contrasting controls with AD individuals, assessed the least distance from point to the curve at every brain voxel, which provided the amyloid-β values with the best trade-off between sensitivity and specificity for AD. Finally, we generated a voxel-wise parametric map only with brain regions showing both sensitivity and specificity higher than 0.85.

      Results

      Remarkably, the regions with the highest sensitivity and specificity for AD dementia were confined to the brain’s default mode network in the precuneus, posterior cingulate, medial prefrontal, and lateral temporal cortices (Fig.1). In contrast, other brain regions with high amyloid-β burden such as the anterior cingulate had low sensitivity and specificity values.

      Conclusions

      These results highlight that although amyloid-β deposition occurs widespread over the cortex, the deposition more strongly associated with dementia are confined to the brain's regions default mode network. Interestingly, our results showed dissociation between the regional levels of amyloid-β burden and the sensitivity and specificity of this burden for a diagnosis of AD. This suggests that the selective regional vulnerability to the toxic effects of Aβ aggregates, at least, plays a role in the progression of AD.
      Figure thumbnail fx1