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Neuropathological basis of magnetic resonance images in aging and dementia

Authors

  • William J. Jagust MD,

    Corresponding author
    1. School of Public Health and Helen Wills Neuroscience Institute, University of California, Berkeley
    • Helen Wills Neuroscience Institute, 132 Barker Hall MC# 3190, University of California, Berkeley, CA 94720-3190
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  • Ling Zheng MD, PhD,

    1. Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles
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  • Danielle J. Harvey PhD,

    1. Division of Biostatistics, Department of Public Health Sciences, School of Medicine, University of California, Davis
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  • Wendy J. Mack PhD,

    1. Department of Preventive Medicine, Keck School of Medicine, University of Southern California
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  • Harry V. Vinters MD,

    1. Departments of Pathology and Laboratory Medicine and Neurology, Brain Research Institute and Neuropsychiatric Institute, David Geffen School of Medicine, University of California, Los Angeles
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  • Michael W. Weiner MD,

    1. Department of Medicine, School of Medicine, University of California, San Francisco
    2. Department of Radiology, School of Medicine, University of California, San Francisco
    3. Department of Psychiatry, School of Medicine, University of California, San Francisco
    4. Department of Neurology, School of Medicine, University of California, San Francisco
    5. Magnetic Resonance Unit, Department of Veterans Affairs Medical Center, San Francisco
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  • William G. Ellis MD,

    1. Department of Pathology, School of Medicine, University of California, Davis, CA
    2. Department of Neurology, School of Medicine, University of California, Davis, CA
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  • Chris Zarow PhD,

    1. Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles
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  • Dan Mungas PhD,

    1. Department of Neurology, School of Medicine, University of California, Davis, CA
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  • Bruce R. Reed PhD,

    1. Department of Neurology, School of Medicine, University of California, Davis, CA
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  • Joel H. Kramer PhD,

    1. Department of Neurology, School of Medicine, University of California, San Francisco
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  • Norbert Schuff PhD,

    1. Department of Radiology, School of Medicine, University of California, San Francisco
    2. Magnetic Resonance Unit, Department of Veterans Affairs Medical Center, San Francisco
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  • Charles DeCarli MD,

    1. Department of Neurology, School of Medicine, University of California, Davis, CA
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  • Helena C. Chui MD

    1. Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles
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Abstract

Objective

Magnetic resonance (MR) imaging is used widely for assessment of patients with cognitive impairment, but the pathological correlates are unclear, especially when multiple pathologies are present.

Methods

This report includes 93 subjects from a longitudinally followed cohort recruited for the study of Alzheimer's disease (AD) and subcortical cerebrovascular disease (CVD). MR images were analyzed to quantify cortical gray matter volume, hippocampal volume, white matter hyperintensities, and lacunes. Neuropathological examination quantified CVD parenchymal pathology, AD pathology (defined as Consortium to Establish a Registry for Alzheimer's Disease scores and Braak and Braak stage), and hippocampal sclerosis. Subjects were pathologically classified as 12 healthy control subjects, 46 AD, 14 CVD, 9 mixed AD/CVD, and 12 cognitively impaired patients without significant AD/CVD pathology. Multivariate models tested associations between magnetic resonance and pathological findings across the entire sample.

Results

Pathological correlates of cortical gray matter volume were AD, subcortical vascular pathology, and arteriosclerosis. Hippocampal volume was related to AD pathology and hippocampal sclerosis, and the effects of hippocampal sclerosis were greater for subjects with low levels of AD pathology. White matter hyperintensities were related to age and to white matter pathology. Number of MRI lacunes was related to subcortical vascular pathology.

Interpretation

In this clinical setting, the presence of lacunes and white matter changes provide a good signal for vascular disease. The neuropathological basis of MR defined cerebral cortical and hippocampal atrophy in aging and dementia is complex, with several pathological processes converging on similar brain structures that mediate cognitive decline. Ann Neurol 2008

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