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Cerebral Cortex Advance Access published online on September 15, 2004
Cerebral Cortex, doi:10.1093/cercor/bhh174
© 2004 by Oxford University Press
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Article

Frontal-Hippocampal Double Dissociation Between Normal Aging and Alzheimer's Disease

Denise Head 1*, Abraham Z. Snyder 2, Laura E. Girton 3, John C. Morris 4, and Randy L. Buckner 5

1 Howard Hughes Medical Institute, One Brookings Drive, St Louis, MO 63130, USA; Department of Psychology, Washington University, St Louis, MO 63130, USA
2 Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO 63110, USA; Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
3 Howard Hughes Medical Institute, One Brookings Drive, St Louis, MO 63130, USA
4 Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
5 Howard Hughes Medical Institute, One Brookings Drive, St Louis, MO 63130, USA; Department of Psychology, Washington University, St Louis, MO 63130, USA; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO 63110, USA; Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO 63110, USA

* To whom correspondence should be addressed. E-mail: dhead{at}artsci.wustl.edu.


  Abstract

Controversy persists regarding whether Alzheimer's disease (AD) is a distinct entity or instead exists on a continuum with nondemented aging. To explore this issue, volumetric analyses of callosal and hippocampal regions were performed on 150 participants aged 18-93 years. Group-level analyses revealed that nondemented age-related differences were greater in anterior than posterior callosal regions and were not augmented by early-stage AD. In contrast, early-stage AD was associated with substantial reduction in hippocampal volume. Examination of the 100 older adults using regression analyses demonstrated age-associated differences in callosal volume that were similar in demented and nondemented individuals. Early-stage AD was again characterized by a marked reduction in hippocampal volume while age alone induced only mild differences in hippocampal volume. As a final analysis, the formal double dissociation was confirmed by comparing the effects of age directly against the effects of dementia. These results suggest a multiple-component model of aging. One process, associated with AD, manifests early and prominently in the medial temporal lobe. A separate process, ubiquitous in aging, affects brain white matter with an anterior-to-posterior gradient and may underlie the executive difficulties common in aging.

Keywords: corpus callosum; dementia; MCI; MRI; white matter.
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