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Frontotemporal dementia: Clinicopathological correlations

Authors

  • Mark S. Forman MD, PhD,

    1. Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA
    2. Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Jennifer Farmer MS,

    1. Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Julene K. Johnson PhD,

    1. Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA
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  • Christopher M. Clark MD,

    1. Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA
    2. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Steven E. Arnold MD,

    1. Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA
    2. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
    3. Department of Pyschiatry, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • H. Branch Coslett MD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Anjan Chatterjee MD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Howard I. Hurtig MD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Jason H. Karlawish MD,

    1. Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA
    2. Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Howard J. Rosen MD,

    1. Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA
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  • Vivianna Van Deerlin MD, PhD,

    1. Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Virginia M.-Y. Lee PhD,

    1. Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA
    2. Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Bruce L. Miller MD,

    1. Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA
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  • John Q. Trojanowski MD, PhD,

    1. Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA
    2. Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Murray Grossman MD, EdD

    Corresponding author
    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
    • Department of Neurology, University of Pennsylvania School of Medicine, 3600 Spruce Street, 3 West Gates, Philadelphia, PA 19104-4283
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Abstract

Objective

Frontotemporal lobar degeneration (FTLD) is characterized by impairments in social, behavioral, and/or language function, but postmortem studies indicate that multiple neuropathological entities lead to FTLD. This study assessed whether specific clinical features predict the underlying pathology.

Methods

A clinicopathological correlation was performed on 90 consecutive patients with a pathological diagnosis of frontotemporal dementia and was compared with an additional 24 cases accrued during the same time period with a clinical diagnosis of FTLD, but with pathology not typically associated with frontotemporal dementia.

Results

Postmortem examination showed multiple pathologies including tauopathies (46%), FTLD with ubiquitin-positive inclusions (29%), and Alzheimer's disease (17%). The pathological groups manifested some distinct demographic, clinical, and neuropsychological features, although these attributes showed only a statistical association with the underlying pathology. FTLD with ubiquitin-positive inclusions was more likely to present with both social and language dysfunction, and motor neuron disease was more likely to emerge in these patients. Tauopathies were more commonly associated with an extrapyramidal disorder. Alzheimer's disease was associated with relatively greater deficits in memory and executive function.

Interpretation

Clinical and neuropsychological features contribute to delineating the spectrum of pathology underlying a patient diagnosed with FTLD, but biomarkers are needed that, together with the clinical phenotype, can predict the underlying neuropathology. Ann Neurol 2006;59:952-962

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