Assessment of dementia risk in aging adults using both FDG-PET and FDDNP-PET imaging

Authors

  • L. M. Ercoli,

    Corresponding author
    • Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA
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  • G. W. Small,

    1. Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA
    2. Alzheimer's Disease Center, University of California, Los Angeles, Los Angeles, CA, USA
    3. Longevity Center, University of California, Los Angeles, Los Angeles, CA, USA
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  • P. Siddarth,

    1. Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA
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  • V. Kepe,

    1. Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA
    2. Alzheimer's Disease Center, University of California, Los Angeles, Los Angeles, CA, USA
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  • S.-C. Huang,

    1. Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA
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  • K. J. Miller,

    1. Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA
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  • H. Lavretsky,

    1. Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA
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  • S. Y. Bookheimer,

    1. Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA
    2. Brain Mapping Center, University of California, Los Angeles, Los Angeles, CA, USA
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  • J. R. Barrio,

    1. Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA
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  • D. H. S. Silverman

    1. Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA
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L. Ercoli, Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA. E-mail: HUlercoli@mednet.ucla.eduU

Abstract

Background

In a previous study, positron emission tomography (PET) with 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles in vitro, identified three subgroups of non-demented subjects according to FDDNP binding patterns: low global (LG) binding; high frontal, parietal, medial temporal binding (HF/PA); and high medial and lateral temporal and posterior cingulate (HT/PC) binding. In this follow-up investigation, we compared 2-deoxy-2-[F-18]fluoro- d-glucose (FDG)-PET cerebral metabolic patterns in the three FDDNP-PET binding subgroups.

Methods

Fifty-four subjects with normal aging (N = 28) or amnestic forms of mild cognitive impairment (N = 26) underwent FDDNP-PET and FDG-PET scanning. Subjects in the LG, HF/PA, and HT/PC FDDNP subgroups were compared according to visual ratings, statistical parametric mapping, and automated region of interest analyses of their FDG-PET data.

Results

The FDDNP-PET subgroups demonstrated different glucose metabolic patterns according to visual ratings, region of interest, and statistical parametric mapping analyses of FDG-PET data. The LG FDDNP subgroup showed no areas of significant hypometabolism relative to the other subgroups and had low Alzheimer's disease risk by FDG-PET standards. The HF/PA FDDNP subgroup demonstrated hypometabolism in bilateral inferior parietal/parietotemporal, bilateral posterior cingulate, perisylvian, mid-temporal gyrus, and dorsolateral prefrontal regions, which is a pattern suggestive of high Alzheimer's disease risk. The HT/PC FDDNP subgroup demonstrated heterogeneous FDG-PET patterns with predominant anterior frontal and anterior temporal hypometabolism, suggestive of mixed etiologies, including fronto-temporal dementia risk.

Conclusions

The FDG-PET data provided independent validation that different patterns of FDDNP-PET binding in non-demented individuals may be associated with differential dementia risk. Copyright © 2012 John Wiley & Sons, Ltd.

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