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Published Online: 1 November 2010

Family History of Alzheimer's Disease and Hippocampal Structure in Healthy People

Markus Donix, M.D., Alison C. Burggren, Ph.D., Nanthia A. Suthana, Ph.D., Prabha Siddarth, Ph.D., Arne D. Ekstrom, Ph.D., Allison K. Krupa, B.S., Michael Jones, B.S., Laurel Martin-Harris, B.A., Linda M. Ercoli, Ph.D., Karen J. Miller, Ph.D., Gary W. Small, M.D., and Susan Y. Bookheimer, Ph.D.Authors Info & Affiliations
Publication: American Journal of Psychiatry
Volume 167, Number 11
https://doi.org/10.1176/appi.ajp.2010.09111575
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Abstract

Objective:

Structural brain changes appear years before the onset of Alzheimer's disease, the leading cause of dementia late in life. Determining risk factors for such presymptomatic brain changes may assist in identifying candidates for future prevention treatment trials. In addition to the e4 allele of the apolipoprotein E gene (APOE-4), the major known genetic risk factor, a family history of Alzheimer's disease also increases the risk to develop the disease, reflecting yet unidentified genetic and, perhaps, nongenetic risks. The authors investigated the influence of APOE-4 genotype and family history risks on cortical thickness in medial temporal lobe subregions among volunteers without cognitive impairment.

Method:

High-resolution magnetic resonance imaging (MRI) and a cortical unfolding method were performed on 26 subjects (APOE-4 carriers: N=13; noncarriers: N=13) with at least one first-degree relative with Alzheimer's disease and 25 subjects (APOE-4 carriers: N=12; noncarriers: N=13) without this risk factor. All subjects (mean age: 62.3 years [SD=10.7]; range=38-86 years) were cognitively healthy.

Results:

Family history of Alzheimer's disease and APOE-4 status were associated with a thinner cortex in the entorhinal region, subiculum, and adjacent medial temporal lobe subfields. Although these associations were additive, family history of Alzheimer's disease explained a greater proportion of the unique variance in cortical thickness than APOE-4 carrier status.

Conclusions:

APOE-4 carrier status and family history of Alzheimer's disease are independently associated with and contribute additively to hippocampal cortical thinning.

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Information & Authors

Information

Published In

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American Journal of Psychiatry
Volume 167 • Number 11 • November 2010
Pages: 1399 - 1406
PubMed: 20686185

History

Received: 4 November 2009
Revision received: 20 January 2010
Accepted: 11 March 2010
Published online: 1 November 2010
Published in print: November 2010

Authors

Affiliations

Markus Donix, M.D.
From the Center for Cognitive Neurosciences, Department of Psychiatry and Biobehavioral Sciences, and Department of Psychology, David Geffen School of Medicine at the University of California Los Angeles, Semel Institute, Los Angeles; the University of California at Los Angeles Center on Aging, Los Angeles; the Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden and the German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany; and the Center for Neuroscience and Department of Psychology, University of California at Davis, Davis, Calif.
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Alison C. Burggren, Ph.D.
From the Center for Cognitive Neurosciences, Department of Psychiatry and Biobehavioral Sciences, and Department of Psychology, David Geffen School of Medicine at the University of California Los Angeles, Semel Institute, Los Angeles; the University of California at Los Angeles Center on Aging, Los Angeles; the Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden and the German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany; and the Center for Neuroscience and Department of Psychology, University of California at Davis, Davis, Calif.
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Nanthia A. Suthana, Ph.D.
From the Center for Cognitive Neurosciences, Department of Psychiatry and Biobehavioral Sciences, and Department of Psychology, David Geffen School of Medicine at the University of California Los Angeles, Semel Institute, Los Angeles; the University of California at Los Angeles Center on Aging, Los Angeles; the Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden and the German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany; and the Center for Neuroscience and Department of Psychology, University of California at Davis, Davis, Calif.
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Prabha Siddarth, Ph.D.
From the Center for Cognitive Neurosciences, Department of Psychiatry and Biobehavioral Sciences, and Department of Psychology, David Geffen School of Medicine at the University of California Los Angeles, Semel Institute, Los Angeles; the University of California at Los Angeles Center on Aging, Los Angeles; the Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden and the German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany; and the Center for Neuroscience and Department of Psychology, University of California at Davis, Davis, Calif.
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Arne D. Ekstrom, Ph.D.
From the Center for Cognitive Neurosciences, Department of Psychiatry and Biobehavioral Sciences, and Department of Psychology, David Geffen School of Medicine at the University of California Los Angeles, Semel Institute, Los Angeles; the University of California at Los Angeles Center on Aging, Los Angeles; the Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden and the German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany; and the Center for Neuroscience and Department of Psychology, University of California at Davis, Davis, Calif.
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Allison K. Krupa, B.S.
From the Center for Cognitive Neurosciences, Department of Psychiatry and Biobehavioral Sciences, and Department of Psychology, David Geffen School of Medicine at the University of California Los Angeles, Semel Institute, Los Angeles; the University of California at Los Angeles Center on Aging, Los Angeles; the Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden and the German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany; and the Center for Neuroscience and Department of Psychology, University of California at Davis, Davis, Calif.
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Michael Jones, B.S.
From the Center for Cognitive Neurosciences, Department of Psychiatry and Biobehavioral Sciences, and Department of Psychology, David Geffen School of Medicine at the University of California Los Angeles, Semel Institute, Los Angeles; the University of California at Los Angeles Center on Aging, Los Angeles; the Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden and the German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany; and the Center for Neuroscience and Department of Psychology, University of California at Davis, Davis, Calif.
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Laurel Martin-Harris, B.A.
From the Center for Cognitive Neurosciences, Department of Psychiatry and Biobehavioral Sciences, and Department of Psychology, David Geffen School of Medicine at the University of California Los Angeles, Semel Institute, Los Angeles; the University of California at Los Angeles Center on Aging, Los Angeles; the Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden and the German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany; and the Center for Neuroscience and Department of Psychology, University of California at Davis, Davis, Calif.
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Linda M. Ercoli, Ph.D.
From the Center for Cognitive Neurosciences, Department of Psychiatry and Biobehavioral Sciences, and Department of Psychology, David Geffen School of Medicine at the University of California Los Angeles, Semel Institute, Los Angeles; the University of California at Los Angeles Center on Aging, Los Angeles; the Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden and the German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany; and the Center for Neuroscience and Department of Psychology, University of California at Davis, Davis, Calif.
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Karen J. Miller, Ph.D.
From the Center for Cognitive Neurosciences, Department of Psychiatry and Biobehavioral Sciences, and Department of Psychology, David Geffen School of Medicine at the University of California Los Angeles, Semel Institute, Los Angeles; the University of California at Los Angeles Center on Aging, Los Angeles; the Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden and the German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany; and the Center for Neuroscience and Department of Psychology, University of California at Davis, Davis, Calif.
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Gary W. Small, M.D.
From the Center for Cognitive Neurosciences, Department of Psychiatry and Biobehavioral Sciences, and Department of Psychology, David Geffen School of Medicine at the University of California Los Angeles, Semel Institute, Los Angeles; the University of California at Los Angeles Center on Aging, Los Angeles; the Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden and the German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany; and the Center for Neuroscience and Department of Psychology, University of California at Davis, Davis, Calif.
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Susan Y. Bookheimer, Ph.D.
From the Center for Cognitive Neurosciences, Department of Psychiatry and Biobehavioral Sciences, and Department of Psychology, David Geffen School of Medicine at the University of California Los Angeles, Semel Institute, Los Angeles; the University of California at Los Angeles Center on Aging, Los Angeles; the Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden and the German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany; and the Center for Neuroscience and Department of Psychology, University of California at Davis, Davis, Calif.
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Notes

Address correspondence and reprint requests to Dr. Bookheimer, Center for Cognitive Neuroscience, Semel Institute, University of California, Los Angeles, 760 Westwood Plaza, Suite 17-369, Los Angeles, CA 90095; [email protected] (e-mail).

Funding Information

Dr. Small has served as a consultant for and/or received lecture fees from Abbott, Brainstorming Co., Dakim, Eisai, Forest, Myriad Genetics, Novartis, Ortho-McNeil, Pfizer, Radica, Siemens, and Medivation; he is also a shareholder with Dakim. Dr. Ercoli has received lecture fees from the Alzheimer's Association speaker's bureau and Keiro Senior Health Services. Drs. Donix, Burggren, Suthana, Siddarth, Ekstrom, Miller, and Bookheimer and Ms. Krupa, Mr. Jones, and Ms. Martin-Harris report no financial relationships with commercial interests.Supported by National Institutes of Health grants P01-AG025831, AG13308, P50-AG16570, MH-AG58156, MH-52453, AG10123, and M01-RR00865; the General Clinical Research Centers Program, the Fran and Ray Stark Foundation Fund for Alzheimer's Disease Research; the Larry L. Hillblom Foundation; and the Max Kade Foundation (Dr. Donix). No company provided support of any kind for this study.

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